IMPAACT 2002: Cognitive Behavioral Therapy and Medication Management for Treatment of Depression in US Youth With HIV

Sponsor
International Maternal Pediatric Adolescent AIDS Clinical Trials Group (Other)
Overall Status
Completed
CT.gov ID
NCT02939131
Collaborator
National Institute of Allergy and Infectious Diseases (NIAID) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), National Institute of Mental Health (NIMH) (NIH)
156
13
2
34.5
12
0.3

Study Details

Study Description

Brief Summary

IMPAACT 2002 is a prospective, multi-site, two-arm, cluster-randomized study to evaluate whether a health and wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention for depression demonstrates improved depression and medical outcomes for HIV-infected youth in the United States (US) compared to enhanced standard care (ESC).

Condition or Disease Intervention/Treatment Phase
  • Behavioral: Health and Wellness Combined Cognitive Behavioral Therapy and a Medication Management Algorithm
  • Behavioral: Enhanced Standard of Care
N/A

Detailed Description

IMPAACT 2002 was a prospective, multi-site, two-arm, cluster-randomized study that evaluated whether a health and wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention for depression demonstrated improved depression outcomes (e.g., decreased depressive symptoms and greater remission and response rates) and medical outcomes (e.g., increased cluster of differentiation 4 (CD4) T-cell count, decreased HIV RNA level) among HIV-infected youth in the US compared to enhanced standard care (ESC). Sites were randomized to either the COMB-R intervention or the ESC control arm. Youth enrolled in the study attended a Screening/Entry Visit and study visits at Weeks 1, 6, 12, and 24. They had two additional follow-up visits at Weeks 36 and 48 for the study team to evaluate if observed effects of the intervention were maintained. The intervention was a treatment for depression that included a manualized Health and Wellness Cognitive Behavioral Therapy and an algorithm-driven Medication Management designed to address the unique challenges faced by this population.

Study Design

Study Type:
Interventional
Actual Enrollment :
156 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
IMPAACT 2002: Combined Cognitive Behavioral Therapy and a Medication Management Algorithm for Treatment of Depression Among Youth Living With HIV in the United States
Actual Study Start Date :
Mar 6, 2017
Actual Primary Completion Date :
Sep 12, 2019
Actual Study Completion Date :
Jan 21, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: COMB-R

Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention

Behavioral: Health and Wellness Combined Cognitive Behavioral Therapy and a Medication Management Algorithm
Behavioral therapy based on a manualized approach developed specifically for youth living with both HIV and depression, using problem-solving, motivational interviewing and cognitive-behavioral strategies to decrease adherence obstacles and increase wellness. The medication management algorithm includes guidance for clinicians on strategies and tactics to treat depression in this population, including factors to consider when deciding on treatments (i.e., drug-drug interactions, side effects).

Active Comparator: Enhanced Standard of Care

Enhanced Standard of Care (ESC)

Behavioral: Enhanced Standard of Care
Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training on current principles for use of medication and psychotherapy in the treatment of depression.

Outcome Measures

Primary Outcome Measures

  1. Depression Outcomes: Quick Inventory of Depression Symptomatology - Self Report (QIDS-SR) Score [Week 24]

    The QIDS-SR ranges from 0-27 and assesses the severity and number of depression symptoms. Data completed through the Audio Computer Assisted Interview (ACASI) system are used for this outcome. A lower score indicates fewer depression symptoms and lower depression symptom severity. Scores for all participants at a site were averaged. The site-specific averages were then analyzed.

  2. Depression Outcomes: Response to Treatment, Defined as a Decrease in QIDS-SR Score by >50% [Week 0 and Week 24]

    We are assessing the percentage of participants with a response to treatment.The percentage of participants at each site with a response was calculated. These percentages were averaged for each treatment and the treatment averages were compared. A response to treatment is considered a decrease in Quick Inventory of Depression Symptomatology, Self Report (QIDS-SR) from Study entry to Week 24 by more than 50%. The week 0 value is generally considered the entry value. Priority is given to the ACASI score at week 0. In certain cases, the week 1 ACASI value is used if there is no ACASI score at week 0, but there is one at week 1. Paper form scores are used for "study entry" if there is no ACASI record, with the value at week 0 prioritized over the value at week 1. Otherwise, ACASI data are used for this outcome. The QIDS-SR is scored from 0 to 27 with a lower score indicating less symptomatology.

  3. Depression Outcomes: Remission, Defined as a QIDS-SR Score <= 5 [Week 24]

    We computed the percentage of participants at each site with remission and then compared the percentages. Remission is defined as a Quick Inventory of Depression Symptomatology, self-report (QIDS-SR) score <= 5. ACASI data are used for this outcome. The QIDS-SR scale is from 0-27 with a lower score indicating tess symptomatology.

  4. Biological Outcomes: Cluster of Differentiation 4 (CD4) Cell Count at Week 24 [Week 24]

    CD4 cell counts are cells/microL (uL). CD4 cell counts of all participants at a site were averaged. The averages were then analyzed.

  5. Biological Outcomes: Plasma HIV RNA Level at Week 24 [Week 24]

    Plasma HIV RNA data are calculated on the log10 scale as log10(RNA copies/mL) For this analysis, HIV-1 RNA values (copies per mL) that were censored below the lower limit of quantification (LLQ) were imputed to be equal to the LLQ - 1. The LLQ was considered to be 40 copies/mL. Viral load was calculated on the log10 scale as log10(RNA copies/mL). Viral load suppression was also measured as copies < 40. The log10 (RNA copies/mL) values were averaged by site and those averages were analyzed.

Secondary Outcome Measures

  1. Adherence Outcomes: Adherence to Anti-HIV Medications - Number of Days in Last 30 With Any Missed Doses [Weeks 24 and 48]

    Adherence to anti-HIV medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report. The first of three questions was to assess the number of days in the last 30 with any missed medication doses.The average number of days for all participants at a site were averaged. The site-specific averages were then analyzed.

  2. Adherence Outcomes: Adherence to Anti-HIV Medications - How Good Participant Was at Taking Medicines as Instructed [Weeks 24 and 48]

    Adherence to anti-HIV medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report. The second of three questions was how good the participant is at taking his medication as instructed in the last 30 days. Response scales are Likert from 1 to 6, with a higher score indicating better adherence. 1=Very poor .... 6=Excellent. The average score for all participants at each site was computed and these site-level summaries were compared across treatments.

  3. Adherence Outcomes: Adherence to Anti-HIV Medications - How Often Did Participant Take Medications as Instructed [Weeks 24 and 48]

    Adherence to anti-HIV medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report. The third of three questions was how often the participant took medication correctly in the last 30 days. Response scales are Likert from 1 to 6, with a higher score indicating better adherence. 1=Never ... 6=Always. The average score for all participants at a site was computed and these site-level summaries were compared across treatments.

  4. Adherence Outcomes: Adherence to Psychiatric Medications - Number of Days in Last 30 With Any Missed Doses [Weeks 24 and 48]

    Adherence to depression medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report for those participants taking depression medications. Three questions were asked; The first of the three questions was to assess the number of days in the last 30 with any missed medication doses.The average number of days for all participants at a site were averaged. The site-specific averages were then analyzed.

  5. Adherence Outcomes: Adherence to Psychiatric Medications - How Good Participant Was at Taking Medications as Instructed [Weeks 24 and 48]

    Adherence to depression medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report tor those participants taking depression medications. The second of three questions was how good the participant is at taking his medication as instructed during the last 30 days. Response scales are Likert from 1 to 6, with a higher score indicating better adherence.1=Very poor .... 6=Excellent. The average score for all participants at each site was computed and these site-level summaries were compared across treatments.

  6. Adherence Outcomes: Adherence to Psychiatric Medications - How Often Did Participant Take Medicines as Instructed [Weeks 24 and 48]

    Adherence to depression medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report for those participants taking depression medications. The third of three questions was how often the participant took medication correctly in the past 30 days. Response scales are Likert from 1 to 6, with a higher score indicating better adherence: 1=Never .... 6=Always. The average score for all participants at each site was computed and these site-level summaries were compared across treatments.

  7. Adherence Outcomes: Adherence to Psychotherapy Sessions [Weeks 1, 6, 12 and 24]

    We computed the number of scheduled counseling sessions attended. The average number of sessions was computed for all participants at each site and these site-level averages were compared across treatments.Where study visits for weeks 0 and 1 were held on the same day, the counseling session for week 1 would have been administered at week 0.

  8. Adherence Outcomes: Adherence to COMB-R Medication Management Sessions [Weeks 1, 6, 12 and 24]

    We computed the number of scheduled medication management sessions (COMB-R only) attended. The average number of sessions was computed for all participants at each site. We took the mean of the site-level averages.

  9. Adherence Outcomes: Adherence to Study Visits [Weeks 0, 1, 6, 12, 24, 36 and 48]

    We computed the number study visits completed as the number of scheduled study visits completed to date as of week 24 and week 48. However in some cases, weeks 0 and 1 visits were done on the same day. In that case, they were counted as separate visits.The average number of visits was computed for all participants at each site and these site-level averages were compared across treatments.

  10. Depression Outcomes: Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) Score Over 48 Weeks. [Week 48]

    The Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) score ranges from 0-27 and assesses the severity and number of depression symptoms. Data completed through the Audio Computer Assisted Interview (ACASI) system were used for this outcome. A lower score indicates fewer depression symptoms and lower depression symptom severity. Scores for all participants at a site were averaged. The site-specific averages were then analyzed.

  11. Depression Outcomes: Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) Response to Treatment Over 48 Weeks, Defined as a Decrease in QIDS-SR Score by > 50% [Week 0 and Week 48]

    A response to treatment was considered to be a decrease in Quick Inventory of Depression Symptomatology, Self Report (QIDS-SR) from Study entry to Week 48 by more than 50%. The week 0 value was generally considered the entry value. Priority was given to the ACASI score at week 0. In certain cases, the week 1 ACASI value was used if there was no ACASI score at week 0, but there was one at week 1. Paper form scores were used for "study entry" if there were no ACASI records, with the value at week 0 prioritized over the value at week 1. Otherwise, ACASI data were used for this outcome. The QIDS-SR was scored from 0 to 27 with a lower score indicating less symptomatology.The percentage of participants with a QIDS-SR response at each site was calculated. These percentages were averaged for each treatment and the treatment averages were compared.

  12. Depression Outcomes: Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) Score Remission Over 48 Weeks [Week 48]

    Remission is defined as a Quick Inventory of Depression Symptomatology, self-report (QIDS-SR) score of 5 or less. ACASI data are used for this outcome. The QIDS-SR scale is from 0-27 with a lower score indicating tower depression symptomatology. We computed the percentage of participants at each site with remission and then compared the site-level percentages across treatments.

  13. Effect of Demographic, Behavioral, and Biological Modifiers on Depression Outcomes: Quick Inventory of Depression Symptomatology (QIDS-SR) Score [Week 48]

    QIDS-SR score (defined in Outcome 15). Effect of moderators on depression outcomes:Demographic: age group, gender, mode of HIV acquisition, initial level of depression (QIDS-SR categorized as severe/very severe vs. moderate or less severity); Biological: baseline CD4 (count/uL categorized as stage 3 [< 200 cells] vs. less than stage 3), nadir CD4 at study entry (based on count/uL and considering worst classification across ages, defined below), plasma HIV RNA suppression status, Center for Disease Control and Prevention (CDC) clinical stage at entry (Stage 3 vs. less than stage 3): Determination of nadir CD4 cell count as Stage 3 was based on the following: If any of the following were true, the overall CD4 nadir cell count was classified as Stage 3: <750 cells at < 1 year of age; < 500 cells at 1-5 years of age; <200 cells at 6+ years of age (from Revised Surveillance Case Definition for HIV Infection - United States, 2014). See analysis section for description of method.

  14. Effect of Demographic, Behavioral, and Biological Modifiers on Depression Outcomes: Response to Treatment [Week 0 and Week 48]

    Response to Treatment (defined in Outcome 16): Effect of moderators on depression outcomes: Demographic: age group, gender, mode of HIV acquisition, initial level of depression (QIDS-SR categorized as severe/very severe vs. moderate or less severity); Biological: baseline CD4 (count/uL categorized as stage 3 [< 200 cells] vs. less than stage 3), nadir CD4 at study entry (based on count/uL and considering worst classification across ages, defined below), plasma HIV RNA suppression status, Center for Disease Control and Prevention (CDC) clinical stage at entry (Stage 3 vs. less than stage 3): Determination of nadir CD4 cell count as Stage 3 was based on the following: If any of the following were true, the overall CD4 nadir cell count was classified as Stage 3: <750 cells at < 1 year of age; < 500 cells at 1-5 years of age; <200 cells at 6+ years of age (from Revised Surveillance Case Definition for HIV Infection - United States, 2014). See analysis section for description of method.

  15. Effect of Demographic, Behavioral, and Biological Modifiers on Depression Outcomes: Remission [Week 48]

    Remission (defined in Outcome 17): Effect of moderators on depression outcomes: Demographic: age group, gender, mode of HIV acquisition, initial level of depression (QIDS-SR categorized as severe/very severe vs. moderate or less severity); Biological: baseline CD4 (count/uL categorized as stage 3 [< 200 cells] vs. less than stage 3), nadir CD4 at study entry (based on count/uL and considering worst classification across ages, defined below), plasma HIV RNA suppression status, Center for Disease Control and Prevention (CDC) clinical stage at entry (Stage 3 vs. less than stage 3): Determination of nadir CD4 cell count as Stage 3 was based on the following: If any of the following were true, the overall CD4 nadir cell count was classified as Stage 3: <750 cells at < 1 year of age; < 500 cells at 1-5 years of age; <200 cells at 6+ years of age (from Revised Surveillance Case Definition for HIV Infection - United States, 2014). See analysis section for description of method.

  16. Behavioral Risk Outcomes: Alcohol Use - Ever Used [Weeks 24 and 48]

    The percent of participants who reported ever using alcohol was computed for each site. These site-level percentages were compared across treatment groups.

  17. Behavioral Risk- Alcohol Use - Past 3 Months Regular Use Frequency [weeks 24 and 48]

    Frequency of alcohol use during the past three months was reported for those participants reporting at least some use ever; frequency was measured on a 5-point Likert scale from 1 to 5 (1=Never, 2=Once or twice, 3 = monthly, 4=weekly, 5 = daily or almost daily). A lower score indicates less alcohol use. The percentage of participants at each site with regular use (3=monthly, 4=weekly, 5=daily) was computed. The site-level percentages were compared across treatments.

  18. Behavioral Risk - Alcohol Use - Number of Drinks Per Day [weeks 24 and 48]

    The number of alcoholic drinks per day on a typical day was reported. The average of the number of drinks for all participants at each site was computed and these site-level averages were compared across treatments. Analysis was limited to those participants reporting at least some use ever.

  19. Behavioral Risk - Alcohol Use - Binge Drinking [Weeks 24 and 48]

    Binge drinking is defined by the number of days with 5 or more drinks in a row (within a couple of hours) during the past 3 months. These numbers were averaged for all participants at each site and the site-level averages were compared across treatments.Analysis was limited to those participants reporting at least some use ever.

  20. Behavioral Risk Outcomes: Tobacco Use- Ever Used [Weeks 24 and 48]

    The percent of participants reporting tobacco use (ever) was computed for each site and these site-level averages were compared across treatments.

  21. Behavioral Risk - Tobacco Use - Past 3 Months Regular Use Frequency [weeks 24 and 48]

    Past three months frequency of tobacco use was measured on a 5-point Likert scale (1=never, 2=once or twice, 3=monthly, 4 = weekly, 5=daily/almost daily). The percentage of participants with regular use (monthly, weekly or daily) was computed. Analysis was limited to those participants reporting at least some use ever.

  22. Behavioral Risk Outcomes: Drug Use - Ever Used [Weeks 24 and 48]

    For each of the following substances (cannabis, cocaine, amphetamine, inhalants, sedatives, hallucinogens, opioids) we computed the percent of participants at each site who reported ever using the substance. We also computed the site-level percentages of participants ever using any illegal substance excluding cannabis.

  23. Behavioral Risk - Drug Use - Past 3 Months Regular Frequency of Use [week 24 and 48]

    Past three months use frequency for cannabis, cocaine, amphetamine, inhalants, sedatives, hallucinogens, opioids was assessed. This was measured on a 5-point Likert scale from 1=Never to 5=almost daily. A lower score indicates less frequent use. Scores were dichotomized as regular use (3=monthly, 4=weekly, 5=daily/almost daily) or low use (1=never, 2=once or twice). The percent of participants who used a substance at regularly, given they ever used it, was computed for each site. We also defined a variable of regular frequency of use for any illegal substance, excluding cannabis.

  24. Behavioral Risk Outcomes: Sex-Risk Behaviors - Sex as Exchange Commodity [Weeks 24 and 48]

    We considered a report of sex as exchange commodity if participant reported either that they gave sex in exchange for money, drugs or shelter or if they bought sex with money, drugs or shelter. This was only reported for participants who said they had had some sex (oral, vaginal or anal) ever. The percent of participants at each site who used sex as an exchange commodity was computed and the site-level percentages were compared across treatments.

  25. Behavioral Risk Outcomes: Sex-Risk Behaviors - Importance of Using Condom [weeks 24 and 48]

    Participant reported importance that participant or partner use a condom on a scale from 0 to 100 with 0=not important at all, 50= about as important as the other things in my life and 100=most important thing in my life.This was only reported for participants who said they had had some sex (oral, vaginal or anal) ever. The average scores were computed for all participants at each site and the site-level averages were compared across treatments.

  26. Behavioral Risk- Sex Risk Behaviors - Confidence in Condom Use [Week 24 and 48]

    Participant reports how confident they are that she/he or partner will use condoms. Reported on a scale from 0-100 with 0=I do not think I will use condoms, 50=I have a 50% chance of using a condom; 100=I think I will definitely use a condom.This was only reported for participants who said they had had some sex (oral, vaginal or anal) ever. The average scores were computed for all participants at each site and the site-level averages were compared across treatments.

  27. Behavioral Risk - Sex Risk Behaviors - Number of Sexual Partners in Past Three Months [week 24 and 48]

    The participant reported the number of sexual partners in the past three months. This was only reported for participants who said they had had some sex (oral, vaginal or anal) ever. The average number of sexual partners was computed for all participants at each site and the site-level summaries were compared across treatment groups.

  28. Behavioral Risk - Sex Risk Behaviors. Low Use Frequency of Condom Use in Last Three Months - Main Partner [week 24 and 48]

    Main partner frequency of condom use was measured on a 5-point Likert scale from 1= always, 2 = more than half the time, 3= about half the time, 4=less than half the time to 5=never. It is only reported if participant reported some anal or vaginal sex in past three months. The worse (higher) score of that reported for vaginal or anal sex is analyzed. For each site we computed the percent of participants reporting low frequency of condom use (score = 3, 4 or 5). The site-level percentages were averaged and the site-level averages were compared across treatments.

  29. Behavioral Risk - Sex Risk Behavior - Low Use Frequency of Condom Use in Past 3 Months - Other Partner [week 24 and 48]

    Condom use frequency for other than main partners was measured on a 5-point Likert scale from 1= always, 2 = more than half the time, 3= about half the time, 4=less than half the time to 5=never. It is only reported if participant reported some anal or vaginal sex in past three months. The worse (higher) score of that reported for vaginal or anal sex is analyzed. For each site we computed the percent of participants reporting low frequency of condom use (score = 3, 4 or 5). The site-level percentages were averaged and the site-level averages were compared across treatments.

  30. To Describe the Implementation Fidelity at COMB-R Sites and the Counseling Strategies and Medication Patterns at ESC Sites: The Total Numbers of Counseling Sessions [over 24 weeks]

    We counted the total numbers of COMB-R and ESC counseling sessions administered over the intervention period (through week 24), including both interim and scheduled visits. The average number of sessions was computed for all participants at each site and those averages were compared across treatments.

  31. Implementation Fidelity (COMB-R Sites) - Count of Participants Having Been Administered Various COMB-R Counseling Approaches [over 24 Weeks]

    For COMB-R; we assessed numbers of participants for whom counselors reported using each type of cognitive behavioral therapy (CBT) approaches over the intervention period. A participant was counted in a specific category if the approach was ever used during the 24 week intervention period.

  32. Counseling Strategies (ESC Sites) - Count of Participants Having Been Administered Various ESC Counseling Approaches [Over 24 weeks]

    We summarized the types of counseling approaches used by the ESC clinicians over the intervention period. A participant was counted in a specific category if the approach was ever used during the 24 week intervention period.

  33. Implementation Fidelity (COMB-R Sites); Medication Management - Number of Sessions [Over 24 Weeks]

    We computed the number of Medication Management (MM) sessions attended by participants in the COMB-R group over 24 weeks including both interim and scheduled visits .We averaged the number of sessions for all participants at each site and then took the mean of the site-level averages.

  34. Implemental Fidelity (COMB-R) - Medication Management - Stages [week 1, 6, 12, 24]

    We summarized the stages of the MM algorithm reported for participants by prescribing clinicians in the COMB-R group. Stage 0 is no medication. Stage 1 is monotherapy with a selective serotonin re-uptake inhibitor (SSRI). Stage 2 is monotherapy with a second SSRI. Stage 3 is monotherapy with a non-SSRI. Stage 4 is combination treatment with two antidepressants or an antidepressant plus lithium. Stages 1 through 3 also allow for partial responders to receive augmentation with selected other psychiatric medications.

  35. Acceptability: Frequency of Psychiatric Medication Use - Percent of Participants on Psychiatric Medications [week 24]

    We assessed whether or not participants were taking psychiatric medications at week 24 and we computed the percent of participants at each site taking psychiatric medications overall and by classes of psychiatric medications. We compared the site-level percentages across treatment groups. Classes of medications included: any psychiatric medication, any antidepressant medication, any regimen with a selective serotonin re uptake inhibitor (SSRI), any regimen with a non-SSRI antidepressant medication, any other non-antidepressant psychiatric medication.

  36. Acceptability - Frequency of Psychiatric Medication Use - Percent of Study Time on Psychiatric Medications Through Week 24 [over 24 weeks]

    For those participants taking each of several classes of psychiatric medications during the first 24 study weeks, we computed the percent of study time during which each participant was taking psychiatric medications of that category. Regimen classes were: any psychiatric medication, any antidepressant medication, single selective serotonin re-uptake inhibitor (SSRI), single non-SSRI, SSRI+other medication, non-SSRI+other medication. Then the average percent of time on each category of medication was computed for all participants at each site. The site-level means were compared across treatments.

  37. Acceptability: Number of Interim Visits - Counseling Sessions [Over 24 Weeks]

    We counted the number of interim visits with the counseling clinician, defined as those outside of the scheduled study visits. The average number for all participants at each site were computed. Site mean numbers were compared across treatments.

  38. Acceptability - Number of Interim Medication Management Visits (COMB-R) [Over 24 weeks]

    We counted the number of interim visits with the prescribing clinician, defined as those outside of the scheduled study visits. We computed the average number of sessions for all participants at each site. We took the mean of those averages.

  39. COMB-R and ESC Acceptability Among Participants [Week 24]

    Client satisfaction was computed as the mean of the 8 questionnaire items. Each is rated on a 4-point Likert scale from 1-4, with 4 being the best acceptability. Items reflected quality of service, degree to which program met participant needs, and satisfaction with and efficacy of the help given. The average score for all participants at each site was computed. Site mean scores were compared across treatments.

  40. COMB-R and ESC Acceptability Among Counseling Clinicians [Week 24]

    Six items were rated on a 4-point Likert scale from 0-3 (0=poor, 1=fair, 2=good, 3=excellent). A higher score indicates better clinician satisfaction with administering the intervention. These questions rated appropriateness, effectiveness, flexibility, ease of use, fit and overall quality of the treatment approach. For each participant's clinician, a mean score of the six items was computed. The average score was computed for the clinicians of all participants at each site. These site-level means were compared between groups.

  41. COMB-R MM and ESC Acceptability Among Prescribing Clinicians [Week 24]

    For each participant's prescribing clinician, we assessed two domains: How easy or difficult it was to follow the treatment plan (ESC) or medication management algorithm (COMB-R) and whether or not participants symptoms improved over the intervention period. These items were assessed on a 5-point Likert scale (0, 1, 2, 3, 4) and reverse scored if necessary so that a higher score reflected that it was easier to follow the algorithm and that the patients' symptoms improved. Average scores at each site were computed and the site-level summaries were compared across treatments.

  42. Grade 3 or Higher Adverse Events (AE), Psychological Hospitalizations, and Suicide Attempts [Over 24 Weeks]

    In this analysis only "new" events were counted; as identified by MedDRA Preferred Term; that is, those which were first reported after study entry. Two types of adverse events were reported: 1) grade 3 or higher signs/symptoms, and 2) grade 3 or higher diagnoses. "Trigger" events (psychiatric hospitalization or suicide attempts) were also reported. For each of these three types of events, the percent of participants at each site with at least one such event was computed. The average of these site-level percentages within each treatment arm were compared. Note, in some cases due to sparseness (few events reported at sites within a treatment group), the lower bound of the 95% confidence interval was less than zero . In those cases, the bounds were truncated to zero.

  43. Grade 3 or Higher Adverse Events (AE), Psychological Hospitalizations, and Suicide Attempts [Over 48 weeks]

    n this analysis only "new" events were counted; as identified by MedDRA Preferred Term; that is, those which were first reported after study entry. Two types of adverse events were reported: 1) grade 3 or higher signs/symptoms, and 2) grade 3 or higher diagnoses. "Trigger" events (psychiatric hospitalization or suicide attempts) were also reported. For each of these three types of events, the percent of participants at each site with at least one such event was computed. The average of these site-level percentages within each treatment arm were compared. Note, in some cases due to sparseness (few events reported at sites within a treatment group), the lower bound of the 95% confidence interval was less than zero . In those cases, the bounds were truncated to zero.

Eligibility Criteria

Criteria

Ages Eligible for Study:
12 Years to 24 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Receiving mental health or HIV-related care at participating US IMPAACT site

  • Confirmed HIV-1 Infection

  • Aware of his or her HIV infection

  • Per clinician assessment, primary diagnosis of nonpsychotic depression, including Major Depressive Disorder, Depression Not Otherwise Specified (NOS), or Dysthymia, as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV or DSM-V criteria

  • Current depressive symptoms that warrant intervention as determined by a score of ≥ 11 on the Quick Inventory of Depressive Symptomatology - Clinician (QIDS-C)

  • Able to communicate in spoken and written English

  • Able and willing to provide written informed assent/consent and able to obtain written parental or guardian permission (if required, as specified in site standard operating procedure (SOP), by State law, and/or Institutional Review Board (IRB) policy) to be screened for and to enroll in IMPAACT 2002

Exclusion Criteria:
  • Known or self-reported history of any psychotic disorder and/or bipolar I or II disorder

  • Severe disorders (more than 6 symptoms) based on DSM-V criteria related to alcohol, cannabis or other substances; or those with moderate symptoms (4 or 5 symptoms) who are also currently experiencing withdrawal or dependence symptoms; within the past month prior to enrollment

  • Per clinician assessment at screening, depression and/or suicidal ideation requiring more intensive treatment than the study provides or at immediate risk of being a danger to themselves or others

  • Per participant report at screening, intends to relocate away from the study site during study participation

  • Currently in therapy with a non-study provider, unless willing to switch to a study-trained provider

  • Has any other condition that, in the opinion of the Investigator of Record (IoR)/designee, would preclude informed assent/consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Southern California - MCA Center (CRS 5048), Alhambra California United States 91803
2 University California, San Diego (CRS 4601) La Jolla California United States 92093
3 David Geffen School of Medicine at UCLA (CRS 5112) Los Angeles California United States 90095
4 Children's Hospital of Colorado (CRS 5052) Aurora Colorado United States 80045
5 Children's Diagnostic and Treatment Center (CRS 5055) Fort Lauderdale Florida United States 33316
6 Emory University School of Medicine (CRS 5030) Atlanta Georgia United States 30308
7 Rush University Medical Center (CRS 5083) Chicago Illinois United States 60612
8 Johns Hopkins University School of Medicine (CRS 5092) Baltimore Maryland United States 21287
9 Bronx-Lebanon Hospital Center (CRS 5114) Bronx New York United States 10457
10 Jacobi Medical Center (CRS 5013) Bronx New York United States 10461
11 Stony Brook University Medical Center (CRS 5040) Stony Brook New York United States 11794
12 St Jude Children's Research Hospital (CRS 6501) Memphis Tennessee United States 38105
13 Texas Children's/Baylor (CRS 3801) Houston Texas United States 77030

Sponsors and Collaborators

  • International Maternal Pediatric Adolescent AIDS Clinical Trials Group
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • National Institute of Mental Health (NIMH)

Investigators

  • Study Chair: Larry Brown, MD, Rhode Island Hospital; Brown University

Study Documents (Full-Text)

More Information

Additional Information:

Publications

Responsible Party:
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT02939131
Other Study ID Numbers:
  • IMPAACT 2002
  • UM1AI068632
  • UM1AI068616
  • UM1AI106716
First Posted:
Oct 19, 2016
Last Update Posted:
Mar 3, 2021
Last Verified:
Mar 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details Once enrollment opened (Dec 20, 2016), sites prepared lists of potential participants. The approach order was randomized in blocks of six. Sites were instructed to approach participants in order by block. A protocol letter of amendment in April 27, 2018 removed this requirement. First enrolled March 6, 2017, and the last enrolled on March 5, 2019
Pre-assignment Detail Sites were randomized to COMB-R or ESC with balancing based on information collected during application to participate and also in a pre-study survey, which gathered grouped data on characteristics of potential participants at each site including sex at birth, age group, mode of HIV transmission, HIV viral suppression status, level of depression.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Health and Wellness Combined Cognitive Behavioral Therapy and a Medication Management Algorithm: Behavioral therapy based on a manualized approach developed specifically for youth living with both HIV and depression, using problem-solving, motivational interviewing and cognitive-behavioral strategies to decrease adherence obstacles and increase wellness. The medication management algorithm includes guidance for clinicians on strategies and tactics to treat depression in this population, including factors to consider when deciding on treatments (i.e., drug-drug interactions, side effects). Enhanced Standard of Care (ESC) Enhanced Standard of Care: Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training on current principles for use of medication and psychotherapy in the treatment of depression.
Period Title: Overall Study
STARTED 81 75
Week 24 Visit 74 72
COMPLETED 70 66
NOT COMPLETED 11 9

Baseline Characteristics

Arm/Group Title COMB-R Enhanced Standard of Care Total
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Health and Wellness Combined Cognitive Behavioral Therapy and a Medication Management Algorithm: Behavioral therapy based on a manualized approach developed specifically for youth living with both HIV and depression, using problem-solving, motivational interviewing and cognitive-behavioral strategies to decrease adherence obstacles and increase wellness. The medication management algorithm includes guidance for clinicians on strategies and tactics to treat depression in this population, including factors to consider when deciding on treatments (i.e., drug-drug interactions, side effects). Enhanced Standard of Care (ESC) Enhanced Standard of Care: Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training on current principles for use of medication and psychotherapy in the treatment of depression. Total of all reporting groups
Overall Participants 81 75 156
Overall site 6 7 13
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
21.5
(2.6)
21.2
(3.0)
21.4
(2.8)
Age, Customized (Count of Participants)
12-18 yrs
14
17.3%
19
25.3%
33
21.2%
19-24 yrs
67
82.7%
56
74.7%
123
78.8%
Sex: Female, Male (Count of Participants)
Female
44
54.3%
38
50.7%
82
52.6%
Male
37
45.7%
37
49.3%
74
47.4%
Race/Ethnicity, Customized (Count of Participants)
White, non-Hispanic
5
6.2%
3
4%
8
5.1%
Black, Non- Hispanic
51
63%
38
50.7%
89
57.1%
Hispanic, regardless of race
19
23.5%
33
44%
52
33.3%
Asian, Pacific Islander
2
2.5%
0
0%
2
1.3%
More than one race
1
1.2%
1
1.3%
2
1.3%
Missing/Unknown
3
3.7%
0
0%
3
1.9%
Region of Enrollment (Count of Participants)
United States
81
100%
75
100%
156
100%
Route of HIV acquisition (Count of Participants)
Perinatal
40
49.4%
43
57.3%
83
53.2%
Behavioral
41
50.6%
32
42.7%
73
46.8%
log10 (HIV viral load copies/mL) (log10 HIV copies/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 HIV copies/mL]
2.2
(1.2)
2.2
(1.3)
2.2
(1.2)
QIDS-SR at study entry (mean) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]
16.1
(4.1)
13.8
(4.2)
15
(4.3)
Taking psychiatric medications at study entry (Count of Participants)
not taking medications
59
72.8%
60
80%
119
76.3%
taking psychiatric medications
22
27.2%
15
20%
37
23.7%
Average of site-level mean age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
21.5
(0.6)
21.3
(1.8)
21.4
(1.3)
Average of site-level % male (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]
44.9
(24.4)
44.6
(24.5)
44.7
(23.4)
Average of site-level % black participants (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]
65.1
(40)
57
(32.6)
60.7
(34.9)
Average of site-level % with perinatal transmission (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]
49.1
(26.3)
56.2
(22.1)
52.9
(23.4)
Average of site-level mean QIDS-SR scores (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]
16.2
(1.3)
14.5
(3.2)
15.3
(2.6)
Average of site-level mean log 10 (HIV viral load copies/mL) (log10 HIV copies/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 HIV copies/mL]
2.2
(0.7)
2.1
(0.3)
2.2
(0.5)
Average of site-level % of participants taking psychiatric medications (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]
28.0
(13.2)
21.4
(19.0)
24.5
(16.3)

Outcome Measures

1. Primary Outcome
Title Depression Outcomes: Quick Inventory of Depression Symptomatology - Self Report (QIDS-SR) Score
Description The QIDS-SR ranges from 0-27 and assesses the severity and number of depression symptoms. Data completed through the Audio Computer Assisted Interview (ACASI) system are used for this outcome. A lower score indicates fewer depression symptoms and lower depression symptom severity. Scores for all participants at a site were averaged. The site-specific averages were then analyzed.
Time Frame Week 24

Outcome Measure Data

Analysis Population Description
All participants who entered QIDS-SR data into the ACASI system were analyzed.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 66 67
Measure site 6 7
Mean (95% Confidence Interval) [units on a scale]
6.7
10.6
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments
Type of Statistical Test Superiority
Comments We tested the null hypothesis that the treatment group means were equal vs. not. The study was designed for at least 80% power to detect an effect size of 0.8 standard deviations (SD), which corresponded to a difference of four points. We assumed an intracluster correlation coefficient (ICC) between 0.02 and 0.16 and allowed for 10% non-evaluability. In a pre-planned interim analysis, we estimated the ICC based on the entry QIDS-SR to be 0.10.
Statistical Test of Hypothesis p-Value 0.01
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.86
Confidence Interval (2-Sided) 95%
-6.79 to -0.94
Parameter Dispersion Type:
Value:
Estimation Comments We subtracted the mean of the ESC group from the mean of the COMB-R group. Because a lower score indicated less severe depressive symptoms, a negative value indicated superiority.
2. Primary Outcome
Title Depression Outcomes: Response to Treatment, Defined as a Decrease in QIDS-SR Score by >50%
Description We are assessing the percentage of participants with a response to treatment.The percentage of participants at each site with a response was calculated. These percentages were averaged for each treatment and the treatment averages were compared. A response to treatment is considered a decrease in Quick Inventory of Depression Symptomatology, Self Report (QIDS-SR) from Study entry to Week 24 by more than 50%. The week 0 value is generally considered the entry value. Priority is given to the ACASI score at week 0. In certain cases, the week 1 ACASI value is used if there is no ACASI score at week 0, but there is one at week 1. Paper form scores are used for "study entry" if there is no ACASI record, with the value at week 0 prioritized over the value at week 1. Otherwise, ACASI data are used for this outcome. The QIDS-SR is scored from 0 to 27 with a lower score indicating less symptomatology.
Time Frame Week 0 and Week 24

Outcome Measure Data

Analysis Population Description
We analyzed data from all participants with ACASI data at weeks 0 and 24.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 66 66
Measure site 6 7
Mean (95% Confidence Interval) [percent]
62.3
17.9
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments
Type of Statistical Test Superiority
Comments We tested the null hypothesis that the treatment group means were equal vs. not.
Statistical Test of Hypothesis p-Value <0.001
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 44.3
Confidence Interval (2-Sided) 95%
23.1 to 65.5
Parameter Dispersion Type:
Value:
Estimation Comments We subtracted the group mean of the site percents with response for the ESC group from that of the COMB-R group. A positive value indicates the COMB-R group had a higher mean percent of participants with response compared to the ESC group.
3. Primary Outcome
Title Depression Outcomes: Remission, Defined as a QIDS-SR Score <= 5
Description We computed the percentage of participants at each site with remission and then compared the percentages. Remission is defined as a Quick Inventory of Depression Symptomatology, self-report (QIDS-SR) score <= 5. ACASI data are used for this outcome. The QIDS-SR scale is from 0-27 with a lower score indicating tess symptomatology.
Time Frame Week 24

Outcome Measure Data

Analysis Population Description
We analyzed data from all participants with an ACASI QIDS-SR score at week 24.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 66 67
Measure site 6 7
Mean (95% Confidence Interval) [percent]
47.9
17.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments
Type of Statistical Test Superiority
Comments We tested the null hypothesis that the treatment group means were equal vs. not.
Statistical Test of Hypothesis p-Value 0.01
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 30.9
Confidence Interval (2-Sided) 95%
8.9 to 52.9
Parameter Dispersion Type:
Value:
Estimation Comments We subtracted the group mean of the site percents with remission for the ESC group from the COMB-R group so a positive value indicates the COMB-R group has more participants with remission.
4. Primary Outcome
Title Biological Outcomes: Cluster of Differentiation 4 (CD4) Cell Count at Week 24
Description CD4 cell counts are cells/microL (uL). CD4 cell counts of all participants at a site were averaged. The averages were then analyzed.
Time Frame Week 24

Outcome Measure Data

Analysis Population Description
All participants with a CD4 cell count at week 24 were analyzed.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 66 71
Measure site 6 7
Mean (95% Confidence Interval) [cells/uL]
703
683
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments
Type of Statistical Test Superiority
Comments We tested the null hypothesis that the treatment group means were equal vs. not.
Statistical Test of Hypothesis p-Value 0.86
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 19
Confidence Interval (2-Sided) 95%
-223 to 262
Parameter Dispersion Type:
Value:
Estimation Comments Group mean for ESC is subtracted from the group mean for COMB-R. The group means are the means of the site mean CD4 cell counts.
5. Primary Outcome
Title Biological Outcomes: Plasma HIV RNA Level at Week 24
Description Plasma HIV RNA data are calculated on the log10 scale as log10(RNA copies/mL) For this analysis, HIV-1 RNA values (copies per mL) that were censored below the lower limit of quantification (LLQ) were imputed to be equal to the LLQ - 1. The LLQ was considered to be 40 copies/mL. Viral load was calculated on the log10 scale as log10(RNA copies/mL). Viral load suppression was also measured as copies < 40. The log10 (RNA copies/mL) values were averaged by site and those averages were analyzed.
Time Frame Week 24

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants with a non-missing HIV RNA copies value at week 24.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 67 73
Measure site 6 7
Mean (95% Confidence Interval) [log10 HIV RNA (copies/mL)]
2.23
2.06
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments
Type of Statistical Test Superiority
Comments We tested the null hypothesis that the treatment group means were equal vs. not.
Statistical Test of Hypothesis p-Value 0.66
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-0.65 to 0.99
Parameter Dispersion Type:
Value:
Estimation Comments We subtracted the group mean for the ESC group from the group mean of the COMB-R group. The group means are the means of the site mean log10 HIV RNA copies/mL.
6. Secondary Outcome
Title Adherence Outcomes: Adherence to Anti-HIV Medications - Number of Days in Last 30 With Any Missed Doses
Description Adherence to anti-HIV medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report. The first of three questions was to assess the number of days in the last 30 with any missed medication doses.The average number of days for all participants at a site were averaged. The site-specific averages were then analyzed.
Time Frame Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants with an ACASI interview at either week 24 or week 48
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 60 65
Measure site 6 7
week 24
4.4
2.3
week 48
4.8
4.7
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments Comparison of COMB-R and ESC groups, number of days in last 30 with any missed HIV medication doses reported at week 24.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.04
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
0.1 to 4.0
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference indicates COMB-R group had a site-level average of more days in last 30 with missed HIV medication doses.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments Comparison of COMB-R and ESC groups, number of days in last 30 with any missed HIV medication doses reported at week 48.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.96
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-5.0 to 5.2
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference reflects greater number of days with missed HIV medication doses in last 30 days for COMB-R group.
7. Secondary Outcome
Title Adherence Outcomes: Adherence to Anti-HIV Medications - How Good Participant Was at Taking Medicines as Instructed
Description Adherence to anti-HIV medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report. The second of three questions was how good the participant is at taking his medication as instructed in the last 30 days. Response scales are Likert from 1 to 6, with a higher score indicating better adherence. 1=Very poor .... 6=Excellent. The average score for all participants at each site was computed and these site-level summaries were compared across treatments.
Time Frame Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for each participants with a response at either week 24 or week 48.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 63 69
Measure site 6 7
Week 24
4.3
4.7
Week 48
4.4
4.2
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments Comparison of COMB-R and ESC groups, how good was participant at taking HIV medication doses; reported at week 24.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.27
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.1 to 0.4
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference means the COMB-R group rated adherence to HIV medications better than the ESC group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments Comparison of COMB-R and ESC groups, how good was participant at taking HIV medication doses; reported at week 48.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.44
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0.9
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate the COMB-R group rated their adherence better than the ESC group.
8. Secondary Outcome
Title Adherence Outcomes: Adherence to Anti-HIV Medications - How Often Did Participant Take Medications as Instructed
Description Adherence to anti-HIV medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report. The third of three questions was how often the participant took medication correctly in the last 30 days. Response scales are Likert from 1 to 6, with a higher score indicating better adherence. 1=Never ... 6=Always. The average score for all participants at a site was computed and these site-level summaries were compared across treatments.
Time Frame Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants with adherence reported at either week 24 or week 48
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 62 69
Measure site 6 7
Week 24
4.8
5.2
Week 48
4.8
4.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments Comparison of COMB-R and ESC groups, how often did participant take HIV medication as instructed; reported at week 24.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.14
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.1 to 0.2
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate the COMB-R group rated their adherence better than the ESC group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments Comparison of COMB-R and ESC groups, how often did participant take HIV medication as instructed; reported at week 48.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.49
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.6 to 1.1
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate the COMB-R group rated their adherence better than the ESC group.
9. Secondary Outcome
Title Adherence Outcomes: Adherence to Psychiatric Medications - Number of Days in Last 30 With Any Missed Doses
Description Adherence to depression medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report for those participants taking depression medications. Three questions were asked; The first of the three questions was to assess the number of days in the last 30 with any missed medication doses.The average number of days for all participants at a site were averaged. The site-specific averages were then analyzed.
Time Frame Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants with adherence to depression medication data reported at either week 24 or week 48. Participants not taking depression medication were excluded.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 28 21
Measure site 6 7
week 24
3.4
1.2
week 48
3.6
6.4
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments Comparison of COMB-R and ESC groups, number of days in last 30 with any missed depression medication doses reported at week 24.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.05
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
0.0 to 4.4
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate those in the COMB-R group had more days with missed depression medications than those in the ESC group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments Comparison of COMB-R and ESC groups, number of days in last 30 with any missed depression medication doses reported at week 48.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.53
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.7
Confidence Interval (2-Sided) 95%
-12.5 to 7.1
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate those in the COMB-R group reported more days with missed doses than those in the ESC group.
10. Secondary Outcome
Title Adherence Outcomes: Adherence to Psychiatric Medications - How Good Participant Was at Taking Medications as Instructed
Description Adherence to depression medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report tor those participants taking depression medications. The second of three questions was how good the participant is at taking his medication as instructed during the last 30 days. Response scales are Likert from 1 to 6, with a higher score indicating better adherence.1=Very poor .... 6=Excellent. The average score for all participants at each site was computed and these site-level summaries were compared across treatments.
Time Frame Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants with adherence to depression medications reported at either week 24 or week 48. Participants not on depression medications were excluded.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 27 21
Measure site 6 7
week 24
4.5
5.2
week 48
4.5
4.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments Comparison of COMB-R and ESC groups, how good was participant at taking depression medication; reported at week 24.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.13
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.5 to 0.2
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate those in the COMB-R group were better at taking medications.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments Comparison of COMB-R and ESC groups, how good was participant at taking depression medication; reported at week 48.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.53
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-1.1 to 2.0
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate those in the COMB-R group were better at taking their medications.
11. Secondary Outcome
Title Adherence Outcomes: Adherence to Psychiatric Medications - How Often Did Participant Take Medicines as Instructed
Description Adherence to depression medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report for those participants taking depression medications. The third of three questions was how often the participant took medication correctly in the past 30 days. Response scales are Likert from 1 to 6, with a higher score indicating better adherence: 1=Never .... 6=Always. The average score for all participants at each site was computed and these site-level summaries were compared across treatments.
Time Frame Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants with adherence to depression medications reported at either week 24 or week 48. Participants not on depression medications were excluded.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 27 21
Measure site 6 7
Week 24
4.8
5.4
Week 48
5.1
4.3
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments Comparison of COMB-R and ESC groups, how often did participant take depression medication as instructed; reported at week 24.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.07
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.3 to 0.1
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate those in the COMB-R group reported better adherence.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments Comparison of COMB-R and ESC groups, how often did participant take depression medication as instructed; reported at week 48.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.28
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-0.8 to 2.3
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate those in the COMB-R group reported better adherence than those in the ESC group.
12. Secondary Outcome
Title Adherence Outcomes: Adherence to Psychotherapy Sessions
Description We computed the number of scheduled counseling sessions attended. The average number of sessions was computed for all participants at each site and these site-level averages were compared across treatments.Where study visits for weeks 0 and 1 were held on the same day, the counseling session for week 1 would have been administered at week 0.
Time Frame Weeks 1, 6, 12 and 24

Outcome Measure Data

Analysis Population Description
We analyzed the number of sessions for all participants entering the study.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 81 75
Measure site 6 7
Mean (95% Confidence Interval) [sessions]
3.5
3.7
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.44
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.6 to 0.3
Parameter Dispersion Type:
Value:
Estimation Comments
13. Secondary Outcome
Title Adherence Outcomes: Adherence to COMB-R Medication Management Sessions
Description We computed the number of scheduled medication management sessions (COMB-R only) attended. The average number of sessions was computed for all participants at each site. We took the mean of the site-level averages.
Time Frame Weeks 1, 6, 12 and 24

Outcome Measure Data

Analysis Population Description
We analyzed data for all COMB-R participants.
Arm/Group Title COMB-R
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention
Measure Participants 81
Measure site 6
Mean (Standard Deviation) [sessions]
3.6
(0.2)
14. Secondary Outcome
Title Adherence Outcomes: Adherence to Study Visits
Description We computed the number study visits completed as the number of scheduled study visits completed to date as of week 24 and week 48. However in some cases, weeks 0 and 1 visits were done on the same day. In that case, they were counted as separate visits.The average number of visits was computed for all participants at each site and these site-level averages were compared across treatments.
Time Frame Weeks 0, 1, 6, 12, 24, 36 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all study participants
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 81 75
Measure site 6 7
week 24
4.7
4.7
week 48
6.4
6.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The average number of scheduled study visits through week 24 was computed for each site. The analysis was of these site-level averages. These values were compared between study groups
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.67
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.4 to 0.3
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments We computed the average number of scheduled study visits through week 48 for each site. We then averaged the site-level values and compared study groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.74
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.7 to 0.5
Parameter Dispersion Type:
Value:
Estimation Comments
15. Secondary Outcome
Title Depression Outcomes: Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) Score Over 48 Weeks.
Description The Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) score ranges from 0-27 and assesses the severity and number of depression symptoms. Data completed through the Audio Computer Assisted Interview (ACASI) system were used for this outcome. A lower score indicates fewer depression symptoms and lower depression symptom severity. Scores for all participants at a site were averaged. The site-specific averages were then analyzed.
Time Frame Week 48

Outcome Measure Data

Analysis Population Description
We analyzed all data from participants with a QIDS-SR score at week 48.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 68 59
Measure site 6 7
Mean (95% Confidence Interval) [units on a scale]
7.09
9.08
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments We tested the null hypothesis that the treatment group means were equal vs. not.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.14
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.99
Confidence Interval (2-Sided) 95%
-4.74 to 0.76
Parameter Dispersion Type:
Value:
Estimation Comments We subtracted the mean of the ESC group from the mean of the COMB-R group. Because a lower score indicated less severe depressive symptoms, a negative value indicated superiority.
16. Secondary Outcome
Title Depression Outcomes: Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) Response to Treatment Over 48 Weeks, Defined as a Decrease in QIDS-SR Score by > 50%
Description A response to treatment was considered to be a decrease in Quick Inventory of Depression Symptomatology, Self Report (QIDS-SR) from Study entry to Week 48 by more than 50%. The week 0 value was generally considered the entry value. Priority was given to the ACASI score at week 0. In certain cases, the week 1 ACASI value was used if there was no ACASI score at week 0, but there was one at week 1. Paper form scores were used for "study entry" if there were no ACASI records, with the value at week 0 prioritized over the value at week 1. Otherwise, ACASI data were used for this outcome. The QIDS-SR was scored from 0 to 27 with a lower score indicating less symptomatology.The percentage of participants with a QIDS-SR response at each site was calculated. These percentages were averaged for each treatment and the treatment averages were compared.
Time Frame Week 0 and Week 48

Outcome Measure Data

Analysis Population Description
We analyzed data from participants with ACASI data at weeks 0 and 48.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 68 58
Measure site 6 7
Mean (95% Confidence Interval) [percent]
58.7
33.4
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments We tested the null hypothesis that the treatment group means were equal vs. not.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.05
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 25.3
Confidence Interval (2-Sided) 95%
0.5 to 50.0
Parameter Dispersion Type:
Value:
Estimation Comments We subtracted the group mean of the site percents with response for the ESC group from that of the COMB-R group. A positive value indicates the COMB-R group had a higher mean percent of participants with response compared to the ESC group.
17. Secondary Outcome
Title Depression Outcomes: Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) Score Remission Over 48 Weeks
Description Remission is defined as a Quick Inventory of Depression Symptomatology, self-report (QIDS-SR) score of 5 or less. ACASI data are used for this outcome. The QIDS-SR scale is from 0-27 with a lower score indicating tower depression symptomatology. We computed the percentage of participants at each site with remission and then compared the site-level percentages across treatments.
Time Frame Week 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants with a week 48 QIDS-SR ACASI score.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 68 59
Measure site 6 7
Mean (95% Confidence Interval) [percent]
43.7
27.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments We tested the null hypothesis that the treatment group means were equal vs. not.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.24
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 16.3
Confidence Interval (2-Sided) 95%
-12.3 to 44.8
Parameter Dispersion Type:
Value:
Estimation Comments We subtracted the group mean of the site percents with remission for the ESC group from the COMB-R group so a positive value indicates the COMB-R group has more participants with remission.
18. Secondary Outcome
Title Effect of Demographic, Behavioral, and Biological Modifiers on Depression Outcomes: Quick Inventory of Depression Symptomatology (QIDS-SR) Score
Description QIDS-SR score (defined in Outcome 15). Effect of moderators on depression outcomes:Demographic: age group, gender, mode of HIV acquisition, initial level of depression (QIDS-SR categorized as severe/very severe vs. moderate or less severity); Biological: baseline CD4 (count/uL categorized as stage 3 [< 200 cells] vs. less than stage 3), nadir CD4 at study entry (based on count/uL and considering worst classification across ages, defined below), plasma HIV RNA suppression status, Center for Disease Control and Prevention (CDC) clinical stage at entry (Stage 3 vs. less than stage 3): Determination of nadir CD4 cell count as Stage 3 was based on the following: If any of the following were true, the overall CD4 nadir cell count was classified as Stage 3: <750 cells at < 1 year of age; < 500 cells at 1-5 years of age; <200 cells at 6+ years of age (from Revised Surveillance Case Definition for HIV Infection - United States, 2014). See analysis section for description of method.
Time Frame Week 48

Outcome Measure Data

Analysis Population Description
All participants in each effect modifier subgroup with ACASI data at week 48 were analyzed. In some cases a site did not have any participants in a given subgroup, in which case an interaction term for that site could not be computed and the site was excluded from the analysis.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 68 59
Measure site 6 7
Sex at birth - Male
8.15
6.11
Sex at birth- Female
6.78
11.53
Age group - Younger (12-18 years)
6.57
10.13
Age Group - Older (19-24 years)
7.00
8.50
Viral Suppression - Suppressed (less than 40 copies/mL)
5.88
9.80
Viral Suppression - Not Suppressed (40 copies/mL or more)
7.06
8.21
QIDS-SR - Severe/Very severe
8.51
11.19
QIDS-SR - Mild/Moderate
5.46
7.94
Transmission - Perinatal
7.61
9.81
Transmission- Behavioral
7.31
9.21
CDC Stage 3
8.25
6.22
CDC Less than Stage 3
7.63
9.18
CD4 Stage 3 (less than 200 cells/uL)
10.00
5.56
CD4 - Less than Stage 3 (200 cells/uL or more)
6.66
9.14
CD4 Nadir Stage 3
6.05
9.18
CD4 Nadir - Less than Stage 3
7.68
9.24
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For QIDS-SR, since a lower score reflects fewer depression symptoms, a positive treatment effect is a negative difference value between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments This is the test of effect modification by sex at birth
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.79
Confidence Interval (2-Sided) 95%
2.30 to 11.28
Parameter Dispersion Type:
Value:
Estimation Comments A positive value indicates that the treatment difference (lower QIDS-SR score with COMB-R than with ESC) was greater for females compared to males.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences.This is equivalent to taking the differences of the treatment effects between subgroups. Note: For QIDS-SR, since a lower score reflects fewer depression symptoms, a positive treatment effect is a negative difference value between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.23
Comments This is the test of effect modification by age group
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.56
Confidence Interval (2-Sided) 95%
-7.05 to 1.93
Parameter Dispersion Type:
Value:
Estimation Comments A negative value indicates the treatment difference is greater for younger compared to older participants.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences.This is equivalent to taking the differences of the treatment effects between subgroups.Note: For QIDS-SR, since a lower score reflects fewer depression symptoms, a positive treatment effect is a negative difference value between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.31
Comments This is the test of the effect modification of viral suppression status
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.77
Confidence Interval (2-Sided) 95%
-8.48 to 2.95
Parameter Dispersion Type:
Value:
Estimation Comments A negative value indicates a greater treatment difference among those with viral suppression at study entry compared to those without viral suppression.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences.This is equivalent to taking the differences of the treatment effects between subgroups.Note: For QIDS-SR, since a lower score reflects fewer depression symptoms, a positive treatment effect is a negative difference value between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.72
Comments This is the test of effect modification by QIDS-SR depression level at study entry.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
-4.29 to 5.95
Parameter Dispersion Type:
Value:
Estimation Comments A positive value indicates a greater treatment difference among those with moderate levels of depression compared to severe depression.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences.This is equivalent to taking the differences of the treatment effects between subgroups. Note: For QIDS-SR, since a lower score reflects fewer depression symptoms, a positive treatment effect is a negative difference value between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.91
Comments This is the test of effect modification by mode of transmission
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-5.91 to 5.31
Parameter Dispersion Type:
Value:
Estimation Comments A negative value would indicate a greater treatment difference for those with perinatal HIV acquisition compared to behavioral acquisition.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences.This is equivalent to taking the differences of the treatment effects between subgroups. Note: For QIDS-SR, since a lower score reflects fewer depression symptoms, a positive treatment effect is a negative difference value between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.57
Comments This is the test of effect modification by HIV CDC stage level
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.33
Confidence Interval (2-Sided) 95%
-3.91 to 6.57
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate a greater treatment effect for those with less than HIV CDC Stage 3 compared to those with CDC Stage 3 HIV illness.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences.This is equivalent to taking the differences of the treatment effects between subgroups. Note: For QIDS-SR, since a lower score reflects fewer depression symptoms, a positive treatment effect is a negative difference value between groups..
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.10
Comments This is the test of effect modification of CD4 Stage 3 at entry.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.93
Confidence Interval (2-Sided) 95%
-1.73 to 13.59
Parameter Dispersion Type:
Value:
Estimation Comments A positive value indicates a greater treatment effect among those with less than Stage 3 CD4 count at entry compared to those with Stage 3 CD4 count.
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences.This is equivalent to taking the differences of the treatment effects between subgroups. Note: For QIDS-SR, since a lower score reflects fewer depression symptoms, a positive treatment effect is a negative difference value between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.58
Comments This is the test of effect modification by Nadir Stage 3 level at study entry.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.57
Confidence Interval (2-Sided) 95%
-7.74 to 4.60
Parameter Dispersion Type:
Value:
Estimation Comments A negative value indicates a greater treatment effect among those with Stage 3 Nadir CD4 compare to those with less than Stage 3 Nadir CD4.
19. Secondary Outcome
Title Effect of Demographic, Behavioral, and Biological Modifiers on Depression Outcomes: Response to Treatment
Description Response to Treatment (defined in Outcome 16): Effect of moderators on depression outcomes: Demographic: age group, gender, mode of HIV acquisition, initial level of depression (QIDS-SR categorized as severe/very severe vs. moderate or less severity); Biological: baseline CD4 (count/uL categorized as stage 3 [< 200 cells] vs. less than stage 3), nadir CD4 at study entry (based on count/uL and considering worst classification across ages, defined below), plasma HIV RNA suppression status, Center for Disease Control and Prevention (CDC) clinical stage at entry (Stage 3 vs. less than stage 3): Determination of nadir CD4 cell count as Stage 3 was based on the following: If any of the following were true, the overall CD4 nadir cell count was classified as Stage 3: <750 cells at < 1 year of age; < 500 cells at 1-5 years of age; <200 cells at 6+ years of age (from Revised Surveillance Case Definition for HIV Infection - United States, 2014). See analysis section for description of method.
Time Frame Week 0 and Week 48

Outcome Measure Data

Analysis Population Description
We analyzed data for every participant with a defined response. In order to have a defined QIDS-SR response the participant had to have data at both week 0 and week 48. In some cases a site did not have any participants in a given subgroup, in which case an interaction term for that site could not be computed and the site was excluded from the analysis.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 68 58
Measure site 6 7
Sex at birth- Male
54.95
67.30
Sex at birth - Female
64.58
7.82
Age group - Younger (12-18 years)
71.11
22.22
Age group - Older (19-24 years)
56.28
43.25
Viral status - Suppressed (less than 40 copies /mL)
66.61
37.93
Viral status - Not Suppressed (40 or more copies/mL)
55.46
35.28
Depression status - Severe/very severe
55.45
30.56
Depression status- Mild/Moderate
58.33
41.31
Mode of transmission - Perinatal
57.14
15.00
Mode of transmission - Behavioral
57.44
48.81
CDC Stage 3
78.13
50.00
CDC less than Stage 3
48.52
40.63
CD4 Stage 3 (less than 200 cells/uL)
61.11
38.89
CD4 - less than stage 3 (200 or more cells/uL)
59.10
34.85
Nadir CD4 Stage 3
86.31
23.00
Nadir CD4 - less than Stage 3
50.79
37.11
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR response, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments This is the test of effect modification by sex at birth.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -67.81
Confidence Interval (2-Sided) 95%
-116.53 to -19.10
Parameter Dispersion Type:
Value:
Estimation Comments A negative value indicates a greater treatment response (higher percent with response in COMB-R than in ESC group) among females compared to males.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR response, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.09
Comments This is the test of effect modification by age group.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 43.08
Confidence Interval (2-Sided) 95%
-8.23 to 94.38
Parameter Dispersion Type:
Value:
Estimation Comments A positive value reflects a greater treatment effect among younger participants compared to older participants.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR response, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.93
Comments This is the test of effect modification by viral suppression status.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.18
Confidence Interval (2-Sided) 95%
-51.13 to 55.49
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would reflect a greater treatment response among those with suppressed viral status at entry compared to those without viral suppression.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR response, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.87
Comments This is the test of effect modification by entry QIDS-SR depression level.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.36
Confidence Interval (2-Sided) 95%
-42.28 to 49.00
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate a greater treatment response for those with severe depressive symptoms at study entry compared to those with moderate depression.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR response, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.17
Comments This is the test of effect modification by mode of transmission.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 41.65
Confidence Interval (2-Sided) 95%
-21.91 to 105.20
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate a larger treatment response for those with perinatal transmission compared to behavioral.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR response, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.17
Comments This is the test of effect modification by HIV CDC stage.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 49.40
Confidence Interval (2-Sided) 95%
-26.02 to 124.83
Parameter Dispersion Type:
Value:
Estimation Comments A positive value reflects a greater treatment response for those with HIV CDC Stage 3 classification compared to those with CDC classification less than Stage 3.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR response, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.71
Comments This is the test of effect modification by CD4 Stage at study entry.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 11.69
Confidence Interval (2-Sided) 95%
-70.76 to 94.15
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would reflect greater treatment response for those with CD4 Stage 3 compared to those with less than Stage 3 CD4.
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR response, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.02
Comments This is the test of effect modification by CD4 Nadir stage at study entry.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 52.48
Confidence Interval (2-Sided) 95%
10.46 to 94.50
Parameter Dispersion Type:
Value:
Estimation Comments A positive value reflects a larger treatment response among those with Stage 3 Nadir CD4 compared to those with less than Stage 3 Nadir CD4.
20. Secondary Outcome
Title Effect of Demographic, Behavioral, and Biological Modifiers on Depression Outcomes: Remission
Description Remission (defined in Outcome 17): Effect of moderators on depression outcomes: Demographic: age group, gender, mode of HIV acquisition, initial level of depression (QIDS-SR categorized as severe/very severe vs. moderate or less severity); Biological: baseline CD4 (count/uL categorized as stage 3 [< 200 cells] vs. less than stage 3), nadir CD4 at study entry (based on count/uL and considering worst classification across ages, defined below), plasma HIV RNA suppression status, Center for Disease Control and Prevention (CDC) clinical stage at entry (Stage 3 vs. less than stage 3): Determination of nadir CD4 cell count as Stage 3 was based on the following: If any of the following were true, the overall CD4 nadir cell count was classified as Stage 3: <750 cells at < 1 year of age; < 500 cells at 1-5 years of age; <200 cells at 6+ years of age (from Revised Surveillance Case Definition for HIV Infection - United States, 2014). See analysis section for description of method.
Time Frame Week 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants with an ACASI QIDS-SR reported at week 48. We computed the percent of participants with remission at week 48 at each site. In some cases a site did not have any participants in a given subgroup, in which case an interaction term for that site could not be computed and the site was excluded from the analysis.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 68 59
Measure site 6 7
Sex at Birth- Male
44.54
56.59
Sex at birth - Female
42.13
7.82
Age Group - Younger (12-18 years)
31.11
22.22
Age Group - Older (19-24 years)
47.94
34.68
Viral Suppression - Suppressed (less than 40 copies/mL)
49.84
28.74
Viral Suppression - not suppressed ( 40 copies/mL or more)
45.74
30.24
QIDS-SR level - Severe/Very severe
32.79
27.78
QIDS-SR level - Mild/Moderate
58.33
35.76
Mode of transmission - Perinatal
35.32
16.43
Mode of transmission - Behavioral
39.85
30.95
CDC Stage 3
40.63
56.67
Less than CDC Stage 3
36.30
23.17
CD4 Stage 3 (less than 200 cells/uL)
44.44
55.56
CD4- less than Stage 3 (200 or more cells/uL)
45.67
24.85
CD4 Nadir Stage 3
50.60
28.00
CD4 Nadir- less than Stage 3
38.03
26.40
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR remission, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.09
Comments This is the test of effect modification by sex at birth
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -45.06
Confidence Interval (2-Sided) 95%
-97.84 to 7.72
Parameter Dispersion Type:
Value:
Estimation Comments A negative value indicates a greater treatment effect (higher percent with remission for COMB-R than for ESC) among females.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR remission, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.95
Comments This is the test of effect modification by age group.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.41
Confidence Interval (2-Sided) 95%
-43.38 to 46.20
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would reflect a larger treatment effect among younger participants compared to older participants.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR remission, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.79
Comments This is the test of effect modification by viral suppression status.
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.59
Confidence Interval (2-Sided) 95%
-40.47 to 51.65
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would reflect a greater treatment effect among those with suppressed viral load compared to those without viral suppression.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR remission, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.42
Comments This is the test of effect modification by QIDS-SR level at entry.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -15.97
Confidence Interval (2-Sided) 95%
-58.88 to 26.94
Parameter Dispersion Type:
Value:
Estimation Comments A negative value would reflect a greater treatment effect among those with moderate depression symptomatology at entry compared to those with severe depression.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR remission, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.68
Comments This is the test of effect modification by mode of transmission.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 9.99
Confidence Interval (2-Sided) 95%
-41.24 to 61.22
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would reflect a greater treatment effect among those with perinatal transmission compared to behavioral transmission.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR remission, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.57
Comments This is the test of effect modification by HIV CDC stage.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -14.21
Confidence Interval (2-Sided) 95%
-70.62 to 42.20
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would reflect a greater treatment response among those with HIV CDC Stage 3 classification compared to those with less than Stage 3 classification.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR remission, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.26
Comments This is the test of effect modification by CD4 Stage.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -44.97
Confidence Interval (2-Sided) 95%
-141.12 to 51.17
Parameter Dispersion Type:
Value:
Estimation Comments A negative value would reflect a greater treatment effect among those with less than Stage 3 CD4 levels compared to those with Stage 3 CD4.
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments An interaction effect is computed based on subgroup differences within sites. The mean subgroup difference is computed for each treatment group and the interaction effect is the difference of those group mean differences. This is equivalent to taking the differences of the treatment effects between subgroups. Note: For the percent of participants with QIDS-SR remission, a positive treatment effect is a positive difference between groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.72
Comments This is the test of effect modification by CD4 nadir stage.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 9.53
Confidence Interval (2-Sided) 95%
-52.97 to 72.02
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would reflect a greater treatment effect by those with Stage 3 CD4 Nadir compared to those with less than Stage 3.
21. Secondary Outcome
Title Behavioral Risk Outcomes: Alcohol Use - Ever Used
Description The percent of participants who reported ever using alcohol was computed for each site. These site-level percentages were compared across treatment groups.
Time Frame Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
All participants responding to the behavioral risk questionnaire at either week 24 or 48
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 69 69
Measure site 6 7
week 24
75.8
66.0
week 48
70.4
76.6
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The percent of participants with alcohol use ever at week 24 were computed for each site. These site-level percentages were compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.26
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 9.9
Confidence Interval (2-Sided) 95%
-8.4 to 28.1
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate site-level percentages were higher in the COMB-R group and vice versa.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The percent of participants with alcohol use ever at week 48 were computed for each site. These site-level percentages were compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.66
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.3
Confidence Interval (2-Sided) 95%
-37.1 to 24.6
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate site-level percentages were higher in the COMB-R group and vice versa.
22. Secondary Outcome
Title Behavioral Risk- Alcohol Use - Past 3 Months Regular Use Frequency
Description Frequency of alcohol use during the past three months was reported for those participants reporting at least some use ever; frequency was measured on a 5-point Likert scale from 1 to 5 (1=Never, 2=Once or twice, 3 = monthly, 4=weekly, 5 = daily or almost daily). A lower score indicates less alcohol use. The percentage of participants at each site with regular use (3=monthly, 4=weekly, 5=daily) was computed. The site-level percentages were compared across treatments.
Time Frame weeks 24 and 48

Outcome Measure Data

Analysis Population Description
All participants with behavior risk responses at week 24 or 48 who also responded that they had used alcohol.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 50 46
Measure site 6 7
week 24
37.0
32.3
week 48
56.9
30.2
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The percent of participants with regular frequency alcohol use at week 24 were computed for each site. These site-level percentages were compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.71
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.7
Confidence Interval (2-Sided) 95%
-22.3 to 31.7
Parameter Dispersion Type:
Value:
Estimation Comments A positive value indicates higher site-level percentages in the COMB-R group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The percent of participants at each site with regular alcohol use at week 48 was computed. These site-level percents were compared across treatments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.10
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 26.7
Confidence Interval (2-Sided) 95%
-6.3 to 59.6
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate higher site-level percentages in the COMB-R group.
23. Secondary Outcome
Title Behavioral Risk - Alcohol Use - Number of Drinks Per Day
Description The number of alcoholic drinks per day on a typical day was reported. The average of the number of drinks for all participants at each site was computed and these site-level averages were compared across treatments. Analysis was limited to those participants reporting at least some use ever.
Time Frame weeks 24 and 48

Outcome Measure Data

Analysis Population Description
All participants with behavior risk data at week 24 or 48 who said they had used alcohol
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 51 47
Measure site 6 7
week 24
1.7
2.8
week 48
2.1
1.9
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The average number of drinks per day reported at week 24 was computed for each site and these site-level averages were compared across treatments.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.09
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-2.6 to 0.2
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate site level averages were higher in the COMB-R group and vice versa.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The site-level average numbers of drinks per day reported at week 48 were computed and these site-level averages were compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.79
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.8 to 1.0
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate site level averages were higher in the COMB-R group and vice versa.
24. Secondary Outcome
Title Behavioral Risk - Alcohol Use - Binge Drinking
Description Binge drinking is defined by the number of days with 5 or more drinks in a row (within a couple of hours) during the past 3 months. These numbers were averaged for all participants at each site and the site-level averages were compared across treatments.Analysis was limited to those participants reporting at least some use ever.
Time Frame Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
All participants with behavior risk responses at week 24 or 48 who also said that they had used alcohol.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 51 46
Measure site 6 7
week 24
1.0
1.1
week 48
0.8
0.8
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The site-level average number of days with binge drinking at week 24 were computed and these site-level averages were compared across treatments.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.87
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.9 to 0.8
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate site level averages were higher in the COMB-R group anc vice versa
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The site-level average number of days with binge drinking reported at week 48 were computed and the site-level averages were compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.99
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.8 to 0.8
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate site level averages were higher in the COMB-R group and vice versa
25. Secondary Outcome
Title Behavioral Risk Outcomes: Tobacco Use- Ever Used
Description The percent of participants reporting tobacco use (ever) was computed for each site and these site-level averages were compared across treatments.
Time Frame Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
All participants with behavior risk data at either week 24 or 48.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 70 68
Measure site 6 7
week 24
42.5
39.3
week 48
48.8
34.1
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The percent of participants with tobacco use ever at week 24 were computed for each site. These site-level percentages were compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.77
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
-19.7 to 26.0
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate site-level percentages were higher in the COMB-R group and vice versa.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The percent of participants with tobacco use ever at week 48 were computed for each site. These site-level percentages were compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.20
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 14.7
Confidence Interval (2-Sided) 95%
-8.9 to 38.4
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate site-level percentages were higher in the COMB-R group.
26. Secondary Outcome
Title Behavioral Risk - Tobacco Use - Past 3 Months Regular Use Frequency
Description Past three months frequency of tobacco use was measured on a 5-point Likert scale (1=never, 2=once or twice, 3=monthly, 4 = weekly, 5=daily/almost daily). The percentage of participants with regular use (monthly, weekly or daily) was computed. Analysis was limited to those participants reporting at least some use ever.
Time Frame weeks 24 and 48

Outcome Measure Data

Analysis Population Description
All participants with behavior risk data at weeks 24 or 48 who said that they had used tobacco.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 35 28
Measure site 6 7
week 24
65.4
50.2
week 48
62.3
41.7
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of regular use of tobacco at week 24. The percent of participants at each site with regular use was computed. These site-level percentages were compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.09
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 15.2
Confidence Interval (2-Sided) 95%
-2.8 to 33.3
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate the site level percentages were higher in the COMB-R group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of regular frequency use of tobacco at week 48. Site level percentages of the numbers of participants with regular tobacco use were computed and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.21
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 20.6
Confidence Interval (2-Sided) 95%
-14.0 to 55.3
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference indicates site-level percentages were higher in the COMB-R group.
27. Secondary Outcome
Title Behavioral Risk Outcomes: Drug Use - Ever Used
Description For each of the following substances (cannabis, cocaine, amphetamine, inhalants, sedatives, hallucinogens, opioids) we computed the percent of participants at each site who reported ever using the substance. We also computed the site-level percentages of participants ever using any illegal substance excluding cannabis.
Time Frame Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
All participants with behavior risk data at weeks 24 and 48.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 70 70
Measure site 6 7
Cannabis, week 24
70.1
62.2
Cannabis, week 48
69.2
56.2
Any illegal substance excluding cannabis, week 24
19.8
15.1
Any illegal substance excluding cannabis, week 48
18.7
19.3
Cocaine, week 24
9.1
9.0
Cocaine, week 48
7.3
11.0
Amphetamines, week 24
8.9
7.0
Amphetamines, week 48
5.7
7.5
Inhalant, week 24
3.0
1.1
Inhalant, week 48
2.9
3.8
Sedative, week 24
7.7
4.2
Sedative, week 48
3.2
6.8
Hallucinogen, week 24
4.7
5.5
Hallucinogen, week 48
5.9
8.2
Opioid, week 24
5.8
3.2
Opioid, week 48
3.0
6.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The site-level percentages of participants ever using marijuana (cannabis) reported at week 24 were computed and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.41
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.9
Confidence Interval (2-Sided) 95%
-12.4 to 28.3
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate higher site-level percentages in the COMB-R group and vice versa.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The site-level percentages of participants ever using marijuana (cannabis) reported at week 48 were computed and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.26
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 13.0
Confidence Interval (2-Sided) 95%
-10.9 to 36.8
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate higher site-level percentages in the COMB-R group and vice versa.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The site-level percentages of participants ever using any illegal substance excluding marijuana (cannabis) reported at week 24 were computed and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.69
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.7
Confidence Interval (2-Sided) 95%
-20.2 to 29.5
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate higher site-level percentages in the COMB-R group and vice versa.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The site-level percentages of participants ever using any illegal substance excluding marijuana (cannabis) reported at week 48 were computed and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.96
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-24.8 to 23.5
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate higher site-level percentages in the COMB-R group and vice versa.
28. Secondary Outcome
Title Behavioral Risk - Drug Use - Past 3 Months Regular Frequency of Use
Description Past three months use frequency for cannabis, cocaine, amphetamine, inhalants, sedatives, hallucinogens, opioids was assessed. This was measured on a 5-point Likert scale from 1=Never to 5=almost daily. A lower score indicates less frequent use. Scores were dichotomized as regular use (3=monthly, 4=weekly, 5=daily/almost daily) or low use (1=never, 2=once or twice). The percent of participants who used a substance at regularly, given they ever used it, was computed for each site. We also defined a variable of regular frequency of use for any illegal substance, excluding cannabis.
Time Frame week 24 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants with substance use data reported at either week 24 or week 48. Note that the overall number of participants analyzed includes cannabis use.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 46 45
Measure site 6 7
Cannabis, week 24
57.3
47.2
Cannabis, week 48
64.9
65.0
any illegal substance, excluding cannabis, week 24
27.8
3.1
any illegal substance, excluding cannabis, week 48
18.3
36.7
cocaine, week 24
0.0
0.0
cocaine, week 48
25.0
0.0
amphetamine, week 24
0.0
0.0
amphetamine, week 48
0.0
44.4
inhalant, week 24
50.0
0.0
inhalant, week 48
50.0
0.0
sedative, week 24
50.0
16.7
sedative, week 48
50.0
55.6
hallucinogen, week 24
0.0
0.0
hallucinogen, week 48
0.0
0.0
opioid, week 24
0.0
25.0
opioid, week 48
0.0
0.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis for regular use of marijuana (cannabis) at week 24. The percent of participants at each site reporting regular use (of those reporting any use) was computed. These site-level percentages were averaged and compared across treatments.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.53
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10.1
Confidence Interval (2-Sided) 95%
-23.9 to 44.1
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference indicates a higher site-level percentage of participants reporting regular use fof marijuana in the COMB-R group compared to the ESC group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of regular use of marijuana (cannabis) at week 48. Of those reporting ever used, the percent at each site reporting regular use was computed. These site-level percentages were averaged and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 1.0
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-35.1 to 34.9
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate higher site-level percentages of regular use of marijuana (cannabis) in the COMB-R group compared to the ESC group.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of regular use of any illegal substance, excluding cannabis, at week 24. Of those reporting ever used, the percent at each site reporting regular use was computed. These site-level percentages were averaged and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.18
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 24.7
Confidence Interval (2-Sided) 95%
-16.2 to 65.5
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate higher site-level percentages of regular substance use in the COMB-R group compared to the ESC group.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of regular use of any illegal substance, excluding cannabis, at week 48. Of those reporting ever used, the percent at each site reporting regular use was computed. These site-level percentages were averaged and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.34
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -18.3
Confidence Interval (2-Sided) 95%
-59.5 to 22.9
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate higher site-level percentages of regular substance use in the COMB-R group compared to the ESC group.
29. Secondary Outcome
Title Behavioral Risk Outcomes: Sex-Risk Behaviors - Sex as Exchange Commodity
Description We considered a report of sex as exchange commodity if participant reported either that they gave sex in exchange for money, drugs or shelter or if they bought sex with money, drugs or shelter. This was only reported for participants who said they had had some sex (oral, vaginal or anal) ever. The percent of participants at each site who used sex as an exchange commodity was computed and the site-level percentages were compared across treatments.
Time Frame Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants who had reported they had ever had sex and with behavioral risk data reported at weeks 24 or 48.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 54 55
Measure site 6 7
week 24
31.6
18.2
week 48
24.2
20.4
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis for week 24. The percentage of participants at a site who reported using sex as a commodity was calculated and the site-level percentages were averaged and compared across treatments.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.29
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 13.4
Confidence Interval (2-Sided) 95%
-12.9 to 39.6
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate higher site-level percents in the COMB-R group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis for week 48. The percentage of participants at a site who reported using sex as a commodity was calculated and the site-level percentages were averaged and compared across treatments.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.70
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.8
Confidence Interval (2-Sided) 95%
-17.0 to 24.5
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate site-level percentages were higher in the COMB-R group
30. Secondary Outcome
Title Behavioral Risk Outcomes: Sex-Risk Behaviors - Importance of Using Condom
Description Participant reported importance that participant or partner use a condom on a scale from 0 to 100 with 0=not important at all, 50= about as important as the other things in my life and 100=most important thing in my life.This was only reported for participants who said they had had some sex (oral, vaginal or anal) ever. The average scores were computed for all participants at each site and the site-level averages were compared across treatments.
Time Frame weeks 24 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants reporting ever having had sex and with behavioral risk data at weeks 24 or 48.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 54 55
Measure site 6 7
week 24
83.6
80.7
week 48
80.2
84.9
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis for week 24. Scores were averaged by site and the site-level averages were averaged and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.71
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-13.7 to 19.4
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference indicates the site-level averages were higher for the COMB-R group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis for week 48. Scores were averaged by site and the site-level averages were averaged and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.44
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.7
Confidence Interval (2-Sided) 95%
-17.5 to 8.1
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate site-level averages were higher in the COMB-R group.
31. Secondary Outcome
Title Behavioral Risk- Sex Risk Behaviors - Confidence in Condom Use
Description Participant reports how confident they are that she/he or partner will use condoms. Reported on a scale from 0-100 with 0=I do not think I will use condoms, 50=I have a 50% chance of using a condom; 100=I think I will definitely use a condom.This was only reported for participants who said they had had some sex (oral, vaginal or anal) ever. The average scores were computed for all participants at each site and the site-level averages were compared across treatments.
Time Frame Week 24 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for everyone who reported having ever had sex and with behavior risk data at weeks 24 or 48.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 54 55
Measure site 6 7
week 24
78.0
70.7
week 48
78.4
80.8
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis for week 24. Scores were averaged by site and the site-level averages were averaged and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.23
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
-5.3 to 19.8
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate site-level averages were higher in the COMB-R group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis for week 48. Scores were averaged by site and the site-level averages were averaged and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.73
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-17.5 to 12.7
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate site-level averages were higher in the COMB-R group.
32. Secondary Outcome
Title Behavioral Risk - Sex Risk Behaviors - Number of Sexual Partners in Past Three Months
Description The participant reported the number of sexual partners in the past three months. This was only reported for participants who said they had had some sex (oral, vaginal or anal) ever. The average number of sexual partners was computed for all participants at each site and the site-level summaries were compared across treatment groups.
Time Frame week 24 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants who reported ever having had sex and who had data at weeks 24 or 48.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 54 55
Measure site 6 7
week 24
1.9
1.4
week 48
1.6
1.2
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis for week 24. Numbers of partners were averaged by site and the site-level averages were averaged and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.24
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-0.4 to 1.5
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate site-level averages were higher in COMB-R group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis for week 48. Numbers of partners were averaged by site and the site-level averages were averaged and compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.22
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.3 to 1.0
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference indicates site-level averages were higher in the COMB-R group.
33. Secondary Outcome
Title Behavioral Risk - Sex Risk Behaviors. Low Use Frequency of Condom Use in Last Three Months - Main Partner
Description Main partner frequency of condom use was measured on a 5-point Likert scale from 1= always, 2 = more than half the time, 3= about half the time, 4=less than half the time to 5=never. It is only reported if participant reported some anal or vaginal sex in past three months. The worse (higher) score of that reported for vaginal or anal sex is analyzed. For each site we computed the percent of participants reporting low frequency of condom use (score = 3, 4 or 5). The site-level percentages were averaged and the site-level averages were compared across treatments.
Time Frame week 24 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants reporting one or more sexual partner in past 3 months with data at week 24 or 48 and who reported vaginal or anal sex.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 37 35
Measure site 6 7
week 24
31.9
40.1
week 48
26.4
48.2
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis for week 24 data. We computed the percent of participants reporting low frequency of condom use in past three months by site, averaged the site-level percents and compared these averages across treatment arms.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.57
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.3
Confidence Interval (2-Sided) 95%
-40.4 to 23.9
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate higher site-level percents of low frequency condom use in COMB-R treatment group and vice versa.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis for week 48 data. We computed the percent of participants reporting low frequency of condom use in past three months by site, averaged the site-level percents and compared these averages across treatment arms.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.15
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -21.8
Confidence Interval (2-Sided) 95%
-53.1 to 9.5
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate higher site-level percentages in the COMB-R group and vice versa.
34. Secondary Outcome
Title Behavioral Risk - Sex Risk Behavior - Low Use Frequency of Condom Use in Past 3 Months - Other Partner
Description Condom use frequency for other than main partners was measured on a 5-point Likert scale from 1= always, 2 = more than half the time, 3= about half the time, 4=less than half the time to 5=never. It is only reported if participant reported some anal or vaginal sex in past three months. The worse (higher) score of that reported for vaginal or anal sex is analyzed. For each site we computed the percent of participants reporting low frequency of condom use (score = 3, 4 or 5). The site-level percentages were averaged and the site-level averages were compared across treatments.
Time Frame week 24 and 48

Outcome Measure Data

Analysis Population Description
We analyzed data for all participants reporting one or more sexual partner in past 3 months and who reported either anal or vaginal sex, with data from weeks 24 or 48.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 33 25
Measure site 6 7
week 24
28.9
35.7
week 48
14.4
52.1
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments We computed the site-level percentages of participants reporting low frequency condom use at week 24, then averaged the site-level percentages by treatment group and compared these group average percents.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.65
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.8
Confidence Interval (2-Sided) 95%
-40.9 to 27.2
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate site level percents were higher in the COMB-R group and vice versa.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments We computed the site-level percentages of participants reporting low frequency condom use at week 48, then averaged the site-level percentages by treatment group and compared these group average percents.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.02
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -37.8
Confidence Interval (2-Sided) 95%
-69.7 to -5.8
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate site-level percentages were higher in the COMB-R group and vice versa.
35. Secondary Outcome
Title To Describe the Implementation Fidelity at COMB-R Sites and the Counseling Strategies and Medication Patterns at ESC Sites: The Total Numbers of Counseling Sessions
Description We counted the total numbers of COMB-R and ESC counseling sessions administered over the intervention period (through week 24), including both interim and scheduled visits. The average number of sessions was computed for all participants at each site and those averages were compared across treatments.
Time Frame over 24 weeks

Outcome Measure Data

Analysis Population Description
We analyzed data for all study participants
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 81 75
Measure site 6 7
Mean (95% Confidence Interval) [sessions]
11.5
9.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments We averaged the number of counseling sessions for each site and compared these site-level averages.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.33
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.5
Confidence Interval (2-Sided) 95%
-3.0 to 8.1
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference indicates COMB-R participants attended more sessions than ESC
36. Secondary Outcome
Title Implementation Fidelity (COMB-R Sites) - Count of Participants Having Been Administered Various COMB-R Counseling Approaches
Description For COMB-R; we assessed numbers of participants for whom counselors reported using each type of cognitive behavioral therapy (CBT) approaches over the intervention period. A participant was counted in a specific category if the approach was ever used during the 24 week intervention period.
Time Frame over 24 Weeks

Outcome Measure Data

Analysis Population Description
We analyzed data for all COMB-R participants with at least one counseling session over the 24 week treatment period.
Arm/Group Title COMB-R
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention
Measure Participants 80
Psychoeducation
80
98.8%
Motivational interviewing
77
95.1%
Adherence training
63
77.8%
Behavioral coping
79
97.5%
Cognitive restructuring
70
86.4%
Problem solving
68
84%
Wellness
74
91.4%
Practice and application
75
92.6%
Homework assignment
76
93.8%
Relapse and wellness plan
59
72.8%
Safety plan
38
46.9%
Booster sessions
26
32.1%
Family communication
40
49.4%
Contingency management
19
23.5%
Emotional regulation
53
65.4%
37. Secondary Outcome
Title Counseling Strategies (ESC Sites) - Count of Participants Having Been Administered Various ESC Counseling Approaches
Description We summarized the types of counseling approaches used by the ESC clinicians over the intervention period. A participant was counted in a specific category if the approach was ever used during the 24 week intervention period.
Time Frame Over 24 weeks

Outcome Measure Data

Analysis Population Description
We analyzed all participants in the ESC group with at least one counseling session.
Arm/Group Title Enhanced Standard of Care
Arm/Group Description Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 75
Supportive/coping with stress
47
58%
Cognitive behavioral
35
43.2%
Focused problem solving
24
29.6%
Interpersonal
15
18.5%
Expressive or emotion focused
12
14.8%
Motivational interviewing or enhancement
12
14.8%
Eclectic or personalized treatment
7
8.6%
Other
5
6.2%
Acceptance and commitment
2
2.5%
Dialectical behavioral
2
2.5%
Relaxation and/or mindfulness
2
2.5%
Substance use focused treatment
1
1.2%
38. Secondary Outcome
Title Implementation Fidelity (COMB-R Sites); Medication Management - Number of Sessions
Description We computed the number of Medication Management (MM) sessions attended by participants in the COMB-R group over 24 weeks including both interim and scheduled visits .We averaged the number of sessions for all participants at each site and then took the mean of the site-level averages.
Time Frame Over 24 Weeks

Outcome Measure Data

Analysis Population Description
We analyzed data for all COMB-R study participants
Arm/Group Title COMB-R
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention
Measure Participants 81
Measure site 6
Mean (Standard Deviation) [sessions]
5.3
(2.2)
39. Secondary Outcome
Title Implemental Fidelity (COMB-R) - Medication Management - Stages
Description We summarized the stages of the MM algorithm reported for participants by prescribing clinicians in the COMB-R group. Stage 0 is no medication. Stage 1 is monotherapy with a selective serotonin re-uptake inhibitor (SSRI). Stage 2 is monotherapy with a second SSRI. Stage 3 is monotherapy with a non-SSRI. Stage 4 is combination treatment with two antidepressants or an antidepressant plus lithium. Stages 1 through 3 also allow for partial responders to receive augmentation with selected other psychiatric medications.
Time Frame week 1, 6, 12, 24

Outcome Measure Data

Analysis Population Description
We analyzed data for all COMB-R participants with a medication management session administered.
Arm/Group Title COMB-R
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention
Measure Participants 78
Stage 0
54
66.7%
Stage 1
19
23.5%
Stage 2
1
1.2%
Stage 3
4
4.9%
Stage 0
46
56.8%
Stage 1
22
27.2%
Stage 2
1
1.2%
Stage 3
4
4.9%
Stage 0
45
55.6%
Stage 1
20
24.7%
Stage 2
3
3.7%
Stage 3
3
3.7%
Stage 0
38
46.9%
Stage 1
25
30.9%
Stage 2
3
3.7%
Stage 3
3
3.7%
40. Secondary Outcome
Title Acceptability: Frequency of Psychiatric Medication Use - Percent of Participants on Psychiatric Medications
Description We assessed whether or not participants were taking psychiatric medications at week 24 and we computed the percent of participants at each site taking psychiatric medications overall and by classes of psychiatric medications. We compared the site-level percentages across treatment groups. Classes of medications included: any psychiatric medication, any antidepressant medication, any regimen with a selective serotonin re uptake inhibitor (SSRI), any regimen with a non-SSRI antidepressant medication, any other non-antidepressant psychiatric medication.
Time Frame week 24

Outcome Measure Data

Analysis Population Description
We analyzed all participants on study at week 24
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 74 72
Measure site 6 7
Any psychiatric medications
49.1
30.4
Any antidepressant medication
44.9
27.5
SSRI
40.7
18.4
non-SSRI
6.4
10.3
Other non-antidepressant psychiatric medication
10.1
15.1
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis for the percent of participants on any psychiatric medication at week 24. Site-level percentages were compared across treatments.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.06
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 18.7
Confidence Interval (2-Sided) 95%
-0.9 to 38.2
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference indicates more participants in the COMB-R group were taking medications, based on site-level percentages.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of the percent of participants on antidepressant medications. Site-level percentages were compared across treatments.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.06
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 17.4
Confidence Interval (2-Sided) 95%
-0.7 to 35.5
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference means the site-level percentages of those taking medications were higher in the COMB-R group.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of the percent of participants on SSRI antidepressant medications. Site-level percentages were compared across treatments.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.02
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 22.4
Confidence Interval (2-Sided) 95%
4.2 to 40.6
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference indicates the site-level percentages of those taking medications were higher in the COMB-R group.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of the percent of participants on non-SSRI antidepressant medications. Site-level percentages were compared across treatments.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.54
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.9
Confidence Interval (2-Sided) 95%
-17.3 to 9.6
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate site-level percentages of those on medication were higher in the COMB-R group.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of the percent of participants on non-antidepressant psychiatric medications. Site-level percentages were compared across treatments.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.60
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.0
Confidence Interval (2-Sided) 95%
-25.4 to 15.4
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate the site-level percentages of those on medications were higher in the COMB-R group.
41. Secondary Outcome
Title Acceptability - Frequency of Psychiatric Medication Use - Percent of Study Time on Psychiatric Medications Through Week 24
Description For those participants taking each of several classes of psychiatric medications during the first 24 study weeks, we computed the percent of study time during which each participant was taking psychiatric medications of that category. Regimen classes were: any psychiatric medication, any antidepressant medication, single selective serotonin re-uptake inhibitor (SSRI), single non-SSRI, SSRI+other medication, non-SSRI+other medication. Then the average percent of time on each category of medication was computed for all participants at each site. The site-level means were compared across treatments.
Time Frame over 24 weeks

Outcome Measure Data

Analysis Population Description
For each class of psychiatric medication, participants who had received it at some time during the first 24 weeks of the study.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 44 27
Measure site 6 7
any psychiatric medication
69.3
73.1
Single SSRI
60.9
62.8
SSRI+other
39.2
55.8
single non-SSRI
59.1
72.5
non-SSRI plus other
64.5
60.6
Any antidepressant
69.8
74.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis comparing site-level mean percents of study time on any psychiatric medication across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.77
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.8
Confidence Interval (2-Sided) 95%
-32.5 to 24.8
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate more time on medication in the COMB-R group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis comparing site-level mean percents of study time on single SSRI psychiatric medication across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.91
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-37.3 to 33.5
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate more study time on medication in the COMB-R group.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis comparing site-level mean percents of study time on SSRI+other psychiatric medication across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.40
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -16.7
Confidence Interval (2-Sided) 95%
-60.2 to 26.9
Parameter Dispersion Type:
Value:
Estimation Comments A positive value would indicate more time on medication in the COMB-R group.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis comparing site-level mean percents of study time on a single non-SSRI psychiatric medication across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.52
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -13.5
Confidence Interval (2-Sided) 95%
-67.0 to 40.1
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate more time on medication in COMB-R group.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis comparing site-level mean percents of study time on non-SSRI+other psychiatric medication across treatment groups. This analysis is unstable because of sparseness.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.96
Comments
Method t-test, 2 sided
Comments Because of sparseness, the confidence intervals for this site-level analysis are very large.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.8
Confidence Interval (2-Sided) 95%
-778.0 to 785.7
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference indicates more time on medication in the COMB-R group. There was data from only one site in the ESC group and 2 sites in the COMB-R group. The confidence interval for the difference is quite large and the test is unreliable.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis comparing site-level mean percents of study time on antidepressant medication across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.74
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.2
Confidence Interval (2-Sided) 95%
-31.4 to 23.0
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would reflect more time on medications in the COMB-R group
42. Secondary Outcome
Title Acceptability: Number of Interim Visits - Counseling Sessions
Description We counted the number of interim visits with the counseling clinician, defined as those outside of the scheduled study visits. The average number for all participants at each site were computed. Site mean numbers were compared across treatments.
Time Frame Over 24 Weeks

Outcome Measure Data

Analysis Population Description
We analyzed data for all study participants
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 81 75
Measure site 6 7
Mean (95% Confidence Interval) [sessions]
7.9
5.3
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments We compared the site-level average number of interim counseling sessions between treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.29
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.7
Confidence Interval (2-Sided) 95%
-2.8 to 8.2
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate the site level average interim counseling sessions was higher in the COMB-R group.
43. Secondary Outcome
Title Acceptability - Number of Interim Medication Management Visits (COMB-R)
Description We counted the number of interim visits with the prescribing clinician, defined as those outside of the scheduled study visits. We computed the average number of sessions for all participants at each site. We took the mean of those averages.
Time Frame Over 24 weeks

Outcome Measure Data

Analysis Population Description
We analyzed data for all COMB-R participants
Arm/Group Title COMB-R
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention
Measure Participants 81
Measure site 6
Mean (Standard Deviation) [sessions]
1.7
(2.1)
44. Secondary Outcome
Title COMB-R and ESC Acceptability Among Participants
Description Client satisfaction was computed as the mean of the 8 questionnaire items. Each is rated on a 4-point Likert scale from 1-4, with 4 being the best acceptability. Items reflected quality of service, degree to which program met participant needs, and satisfaction with and efficacy of the help given. The average score for all participants at each site was computed. Site mean scores were compared across treatments.
Time Frame Week 24

Outcome Measure Data

Analysis Population Description
All participants with at least one counseling clinician, prescribing clinician or participant acceptability questionnaire completed
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 68 70
Measure site 6 7
Mean (95% Confidence Interval) [units on a scale]
3.67
3.47
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The average score for all participants at each site was computed. These site-level averages were compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.03
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.20
Confidence Interval (2-Sided) 95%
0.02 to 0.38
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference indicates higher site-level averages in the COMB-R group.
45. Secondary Outcome
Title COMB-R and ESC Acceptability Among Counseling Clinicians
Description Six items were rated on a 4-point Likert scale from 0-3 (0=poor, 1=fair, 2=good, 3=excellent). A higher score indicates better clinician satisfaction with administering the intervention. These questions rated appropriateness, effectiveness, flexibility, ease of use, fit and overall quality of the treatment approach. For each participant's clinician, a mean score of the six items was computed. The average score was computed for the clinicians of all participants at each site. These site-level means were compared between groups.
Time Frame Week 24

Outcome Measure Data

Analysis Population Description
All participants with at least one counseling clinician, prescribing clinician or participant acceptability questionnaire completed.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 68 71
Measure site 6 7
Mean (95% Confidence Interval) [units on a scale]
2.26
2.33
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The average of scores for all participants' clinicians at each site was computed and these site-level averages were compared across treatments.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.69
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.43 to 0.29
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate the site-level averages were higher in the COMB-R group compared to the ESC group and vice versa
46. Secondary Outcome
Title COMB-R MM and ESC Acceptability Among Prescribing Clinicians
Description For each participant's prescribing clinician, we assessed two domains: How easy or difficult it was to follow the treatment plan (ESC) or medication management algorithm (COMB-R) and whether or not participants symptoms improved over the intervention period. These items were assessed on a 5-point Likert scale (0, 1, 2, 3, 4) and reverse scored if necessary so that a higher score reflected that it was easier to follow the algorithm and that the patients' symptoms improved. Average scores at each site were computed and the site-level summaries were compared across treatments.
Time Frame Week 24

Outcome Measure Data

Analysis Population Description
Prescribing clinician responses for all participants with at least one counseling clinician, prescribing clinician or participant acceptability questionnaire completed. For the ESC group, prescribing clinicians sometimes did not complete the questions if participant was not on medication for depression.
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 69 40
Measure site 6 7
Mean (95% Confidence Interval) [units on a scale]
3.05
2.40
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments The average scores for all participants' prescribing clinicians at each site were computed and these site-level averages were compared across treatment groups.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.004
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.26 to 1.03
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference would indicate site-level averages were higher for the COMB-R group than the ESC group and vice versa.
47. Secondary Outcome
Title Grade 3 or Higher Adverse Events (AE), Psychological Hospitalizations, and Suicide Attempts
Description In this analysis only "new" events were counted; as identified by MedDRA Preferred Term; that is, those which were first reported after study entry. Two types of adverse events were reported: 1) grade 3 or higher signs/symptoms, and 2) grade 3 or higher diagnoses. "Trigger" events (psychiatric hospitalization or suicide attempts) were also reported. For each of these three types of events, the percent of participants at each site with at least one such event was computed. The average of these site-level percentages within each treatment arm were compared. Note, in some cases due to sparseness (few events reported at sites within a treatment group), the lower bound of the 95% confidence interval was less than zero . In those cases, the bounds were truncated to zero.
Time Frame Over 24 Weeks

Outcome Measure Data

Analysis Population Description
This is the analysis for the Week 24 data. We count a participant if any new qualifying event was reported prior to the week 24 upper window (+30 days).
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 81 75
Measure site 6 7
Week 24, Mean % with Grade 3+ signs/symptoms
9.27
9.11
Week 24, Mean % with Grade 3+ diagnoses
10.48
7.92
Week 24, Mean % with AE trigger event
5.59
1.19
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of new Grade 3+ signs/symptoms through week 24. The percent of participants at each site with at least one such event was computed. The average of these site-level percents was calculated for each treatment arm. These averages were compared.
Type of Statistical Test Superiority
Comments We tested the null hypothesis that the treatment group means were equal vs. not.
Statistical Test of Hypothesis p-Value 0.98
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-14.04 to 14.36
Parameter Dispersion Type:
Value:
Estimation Comments We subtract group mean for ESC from group mean for COMB-R. The group means are the means of the site-level percentages of participants with events.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of new Grade 3+ diagnoses through week 24.The percent of participants at each site with at least one such event was computed. The average of these site-level percents was calculated for each treatment arm. These averages were compared.
Type of Statistical Test Superiority
Comments We tested the null hypothesis that the treatment group means were equal vs. not.
Statistical Test of Hypothesis p-Value 0.60
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.57
Confidence Interval (2-Sided) 95%
-7.85 to 12.98
Parameter Dispersion Type:
Value:
Estimation Comments We subtracted the group mean for the ESC group from that of the COMB-R group. The group mean is the mean of the site-specific percentages of participants with events.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of the triggering events (psychiatric hospitalizations or suicide attempts) through week 24. A participant is counted once if they had reported any such event prior to the upper bound of the week 24 window. The percent of participants at each site with at least one such event were computed.The average of these site-level percents was calculated for each treatment arm. These averages were compared.
Type of Statistical Test Superiority
Comments We tested the null hypothesis that the treatment group means were equal vs. not.The group mean is the mean of the site-specific percentages of participants with events as defined above.
Statistical Test of Hypothesis p-Value 0.17
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.40
Confidence Interval (2-Sided) 95%
-2.21 to 11.02
Parameter Dispersion Type:
Value:
Estimation Comments The ESC group mean percent of participants reporting a trigger event was subtracted from the COMB-R group mean.
48. Secondary Outcome
Title Grade 3 or Higher Adverse Events (AE), Psychological Hospitalizations, and Suicide Attempts
Description n this analysis only "new" events were counted; as identified by MedDRA Preferred Term; that is, those which were first reported after study entry. Two types of adverse events were reported: 1) grade 3 or higher signs/symptoms, and 2) grade 3 or higher diagnoses. "Trigger" events (psychiatric hospitalization or suicide attempts) were also reported. For each of these three types of events, the percent of participants at each site with at least one such event was computed. The average of these site-level percentages within each treatment arm were compared. Note, in some cases due to sparseness (few events reported at sites within a treatment group), the lower bound of the 95% confidence interval was less than zero . In those cases, the bounds were truncated to zero.
Time Frame Over 48 weeks

Outcome Measure Data

Analysis Population Description
This is the analysis for the Week 48 data. We count a participant if any new qualifying event was reported prior to the week 48 upper window (+30 days).
Arm/Group Title COMB-R Enhanced Standard of Care
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Enhanced Standard of Care (ESC) Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training
Measure Participants 81 75
Measure site 6 7
Week 48, Mean % with Grade 3+ sign/symptoms
13.12
12.98
Week 48, Mean % with Grade 3+ diagnoses
19.22
13.57
Week 48, Mean % with AE trigger event
6.88
3.87
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of new Grade 3+ signs/symptoms through week 48. The percent of participants at each site with at least one such event was computed. The average of these site-level percents was calculated for each treatment arm. These averages were compared.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.98
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
-13.85 to 14.13
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference indicates more participants with events in the COMB-R group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of new Grade 3+ diagnoses through week 48. The percent of participants at each site with at least one such event was computed. The average of these site-level percents was calculated for each treatment arm. These averages were compared.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.40
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.64
Confidence Interval (2-Sided) 95%
-8.60 to 19.89
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference indicates more participants with events in the COMB-R group.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection COMB-R, Enhanced Standard of Care
Comments This is the analysis of new trigger events through week 48. The percent of participants at each site with at least one such event was computed. The average of these site-level percents was calculated for each treatment arm. These averages were compared.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.44
Comments
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.01
Confidence Interval (2-Sided) 95%
-5.27 to 11.29
Parameter Dispersion Type:
Value:
Estimation Comments A positive difference indicates more participants with events in the COMB-R group.

Adverse Events

Time Frame The adverse event data were collected over the 48 weeks of the study duration.
Adverse Event Reporting Description At entry, all diagnoses and signs/symptoms occurring within 30 days of entry were collected. Post-entry, all new diagnoses and signs/symptoms of ≥Grade 3 were collected. Laboratory events related to an adverse event or hospitalization were collected. Suicide attempts and psychological hospitalizations were also collected. The Division of AIDS (DAIDS) AE Grading Table (Corrected version 2.1) and EAE Manual (V2.0) were used. All eligible participants who initiated study treatment are included.
Arm/Group Title COMB-R Enhanced Standard of Care (ESC)
Arm/Group Description Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training.
All Cause Mortality
COMB-R Enhanced Standard of Care (ESC)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/81 (0%) 0/75 (0%)
Serious Adverse Events
COMB-R Enhanced Standard of Care (ESC)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 6/81 (7.4%) 6/75 (8%)
Hepatobiliary disorders
Cholecystitis acute 1/81 (1.2%) 0/75 (0%)
Infections and infestations
Appendicitis 0/81 (0%) 1/75 (1.3%)
Pneumonia 0/81 (0%) 1/75 (1.3%)
Psychiatric disorders
Depression 0/81 (0%) 1/75 (1.3%)
Major depression 1/81 (1.2%) 0/75 (0%)
Mental disorder 1/81 (1.2%) 0/75 (0%)
Substance-induced psychotic disorder 0/81 (0%) 1/75 (1.3%)
Suicide attempt 3/81 (3.7%) 2/75 (2.7%)
Other (Not Including Serious) Adverse Events
COMB-R Enhanced Standard of Care (ESC)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 50/81 (61.7%) 49/75 (65.3%)
Gastrointestinal disorders
Abdominal pain 4/81 (4.9%) 5/75 (6.7%)
Diarrhoea 0/81 (0%) 4/75 (5.3%)
General disorders
Fatigue 1/81 (1.2%) 6/75 (8%)
Infections and infestations
Pneumonia bacterial 0/81 (0%) 4/75 (5.3%)
Metabolism and nutrition disorders
Decreased appetite 1/81 (1.2%) 4/75 (5.3%)
Nervous system disorders
Disturbance in attention 0/81 (0%) 10/75 (13.3%)
Lethargy 0/81 (0%) 8/75 (10.7%)
Psychiatric disorders
Anxiety 5/81 (6.2%) 2/75 (2.7%)
Depressed mood 3/81 (3.7%) 11/75 (14.7%)
Depression 25/81 (30.9%) 12/75 (16%)
Insomnia 1/81 (1.2%) 10/75 (13.3%)
Irritability 0/81 (0%) 11/75 (14.7%)
Major depression 22/81 (27.2%) 25/75 (33.3%)
Persistent depressive disorder 7/81 (8.6%) 10/75 (13.3%)
Suicidal ideation 4/81 (4.9%) 5/75 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title IMPAACT Clinicaltrials.gov Coordinator
Organization Family Health International (FHI 360)
Phone (919) 405-1429
Email IMPAACT.ctgov@fstrf.org
Responsible Party:
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT02939131
Other Study ID Numbers:
  • IMPAACT 2002
  • UM1AI068632
  • UM1AI068616
  • UM1AI106716
First Posted:
Oct 19, 2016
Last Update Posted:
Mar 3, 2021
Last Verified:
Mar 1, 2021