Comparing PI-Based to a nNRTI-based ART for Clearance of Plasmodium Falciparum Parasitemia in HIV-Infected
Study Details
Study Description
Brief Summary
The purpose of this study was to see if antiretroviral therapy (ART) is safe and works at getting rid of malaria in blood and to see whether one type of ART is better than another. This study may offer information for further research in looking at whether ART plays a role in the prevention and treatment of malaria.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
A5297 was a Phase I/II, open-label, proof of concept, two-step, two-arm, randomized controlled clinical trial (RCT) to test the superiority of lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) to non-nucleoside reverse transcriptase (nNRTI)-based ART for clearance of Plasmodium falciparum (Pf) subclinical parasitemia (SCP).
The study consisted of two steps. At study Step 1 entry, participants were randomized 1:1 to either LPV/r-based ART or nNRTI-based ART for 15 days. In study Step 2, all participants received nNRTI-based ART and TMP/SMX prophylaxis for 15 days. The total study duration was 30 days.
Study visits occurred every 3 days in Step 1, and every 5 days in Step 2. At each study visit, 2 samples were taken for measurement of parasite density, except day 15 and day 30 at which 3 samples were taken.
Adverse events which occurred after randomization were also recorded. Signs/symptoms and diagnoses were evaluated at each visit, while safety labs (including Hemoglobin, hematocrit, white blood cell count (WBC), differential WBC, platelet count, and absolute neutrophil count (ANC), glucose, electrolytes (sodium, potassium, chloride, bicarbonate), total bilirubin, AST (SGOT), ALT (SGPT), albumin, alkaline phosphatase, and creatinine) were taken at day 15 and day 30, or if indicated at other study visits.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LPV/r-based ART Participants were prescribed to LPV/r-based antiretroviral therapy (ART) for 15 days, which includes lopinavir/ritonavir plus emtricitabine/tenofovir disoproxil fumarate; followed by an nNRTI-based ART, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. |
Drug: Lopinavir/ritonavir
Participants received two 200 mg/50 mg tablets of lopinavir/ritonavir orally twice daily.
Other Names:
Drug: Emtricitabine/tenofovir disoproxil fumarate
Participants received one 200 mg/300 mg tablet of Emtricitabine/tenofovir disoproxil fumarate orally once daily.
Other Names:
Drug: Efavirenz
Participants received one 600 mg tablet of efavirenz orally once daily.
Other Names:
Drug: Nevirapine
If unable to take efavirenz, participants received on 200 mg tablet of nevirapine orally once daily.
Other Names:
Drug: Trimethoprim/sulfamethoxazole
Participants received one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily.
Other Names:
|
| Experimental: nNRTI-based ART Participants were prescribed to nNRTI-based ART for 15 days, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, followed by an nNRTI-based ART and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. |
Drug: Emtricitabine/tenofovir disoproxil fumarate
Participants received one 200 mg/300 mg tablet of Emtricitabine/tenofovir disoproxil fumarate orally once daily.
Other Names:
Drug: Efavirenz
Participants received one 600 mg tablet of efavirenz orally once daily.
Other Names:
Drug: Nevirapine
If unable to take efavirenz, participants received on 200 mg tablet of nevirapine orally once daily.
Other Names:
Drug: Trimethoprim/sulfamethoxazole
Participants received one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of Participants With Plasmodium Falciparum (Pf) Subclinical Parasitemia (SCP) Clearance [Day 15 (3 samples collected, separated by at least 5 hours and all three collected within 24-hours)]
Pf SCP clearance defined by polymerase chain reaction (PCR) < 10 parasites/µL on three consecutive occasions within a 24-hour period. If a participant had missing data on day 15, they were considered as not having clearance.
Secondary Outcome Measures
- Time to First Pf SCP Clearance [From study entry up to day 30]
Time to clearance is defined by time to first measurement with PCR < 10 parasites/µL, and is evaluated as the point estimate and 95% CI for the day when 50% of participants cleared parasite.
- Log10(Pf Parasite Density) [Entry, days 3, 6, 9, 12, 15, 20, 25, 30]
Pf parasite density was determined by PCR. If parasite density equals 0, the value is set to 0.01 before log10 transformation. The value 0.01 was chosen based on the smallest observed parasite density value of 0.017.
- Change in log10(Pf Parasite Density) From Entry to Day 30 [Entry, Day 30]
Change is evaluated as log10(Pf parasite density) at day 30 minus log10(Pf parasite density) at entry. Change is evaluated in four groups: Randomized to nNRTI-based ART with continued Pf SCP at day 15 Randomized to nNRTI-based ART with clearance of Pf SCP at day 15 Randomized to LPV/r-based ART with continued Pf SCP at day 15 Randomized to LPV/r-based ART with clearance of Pf SCP at day 15
- Number of Participants With Uncomplicated Clinical Malaria [From study entry to day 30]
Uncomplicated clinical malaria is defined as the presence of non-severe fever/symptoms and parasitemia without organ complication.
- Number of Participants With Detectable Pf Gametocyte Density [Entry, days 3, 6, 9, 12, 15, 20, 25, 30]
Number of participants with detectable Pf gametocyte density as determined by PCR. Due to the large number of undetectable results, this outcome was measured as dichotomous.
- Change in log10(Pf Gametocyte Density) From Entry to Day 30 [Entry, Day 30]
Change in log10(Pf gametocyte density) as evaluated using a Hodges-Lehmann estimate from entry to day 30 is evaluated in two groups: Randomized to nNRTI-based ART with continued Pf SCP at day 15 Randomized to LPV/r-based ART with continued Pf SCP at day 15 Analysis was not conducted in either group with clearance at day 15 due to the small sample size and high number of undetectable samples in both clearance groups at entry and day 30.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
HIV-1 infection
-
CD4+ count > 200 and < 500 cells/mm^3 obtained within 30 days prior to study entry at a DAIDS-approved laboratory.
-
Pf SCP confirmed in a laboratory approved to conduct parasitemia microscopy. Note: Pf SCP defined as meeting all three of the following criteria within 72 hours prior to study entry:
-
Microscopy confirmed parasitemia (see section 6.3.6 and the A5297 Manual of Procedures [MOPS])
-
An oral temperature < 37.5°C.
-
The absence of Grade 2 or greater signs or symptoms thought to be related to clinical malaria including:
-
headache
-
malaise or fatigue
-
abdominal discomfort
-
muscle or joint pain
-
fever
-
chills
-
perspiration
-
anorexia
-
vomiting
-
other signs or symptoms thought to be related to clinical malaria
-
Certain laboratory values obtained within 14 days prior to study entry, as detailed in section 4.1.4 of the protocol.
-
Hepatitis B surface antigen (HBsAg) negative within 30 days prior to entry.
-
Female study volunteers of reproductive potential have a negative serum or urine pregnancy test performed within 72 hours prior to entry.
-
All study volunteers agree not to participate in a conception process (eg, active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) for study duration. If participating in sexual activity that could lead to pregnancy, must agree to use two reliable forms of contraceptive simultaneously while receiving protocol-specified medications. One form of contraceptive must be a barrier method if a participant receives EFV. Participants must agree to continue the use of two contraceptives for 6 months after stopping EFV and 6 weeks after stopping all other protocol-specified medications.
-
Study volunteers who are not of reproductive potential are eligible without requiring the use of a contraceptive.
-
Ability and willingness of participant or legal guardian/representative to provide informed consent.
-
Willing and able to return to the clinic twice to three times a day for study visits.
Exclusion Criteria:
Step 1: Exclusion Criteria
-
Previous history or current use of ART.
-
Single dose NVP or dual therapies used for Prevention of mother-to-child transmission (PMTCT) within 2 years prior to entry.
-
Use of any medication with antimalarial activity, including TMP/SMX (see list of prohibited medications in the A5297 Manual of Procedures (MOPS)), within 14 days prior to study entry.
-
Confirmed or clinically suspected OIs (including but not limited to tuberculosis, clinical malaria, PCP), or other pulmonary or gastrointestinal infections for which potential participants did not complete treatment more than 30 days prior to enrollment or have signs and symptoms during screening.
-
Breastfeeding.
-
Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
-
Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
-
Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry.
-
Results suggestive of active pulmonary disease from a chest x-ray performed within 30 days prior to study entry.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601) | Eldoret | Kenya | 30100 | |
| 2 | Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501) | Kericho | Kenya | 20200 | |
| 3 | Kisumu Crs (31460) | Kisumu | Kenya | 40100 | |
| 4 | College of Med. JHU CRS (30301) | Blantyre | Malawi | ||
| 5 | Joint Clinical Research Centre (JCRC) (12401) | Kampala | Uganda |
Sponsors and Collaborators
- AIDS Clinical Trials Group
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Study Chair: Johnstone Kumwenda, FRCP, College of Medicine-Johns Hopkins Project
- Study Chair: Douglas Shaffer, MD, MHS, Kenya Medical Research Institute/Walter Reed Project
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004
- Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010
Publications
None provided.- ACTG A5297
- 1U01AI068636
Study Results
Participant Flow
| Recruitment Details | Participants were recruited from 5 clinics in Africa. The first participant enrolled on January 10, 2014. The last participant enrolled on May 20, 2016. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | LPV/R-based ART | nNRTI-based ART |
|---|---|---|
| Arm/Group Description | Participants were prescribed to LPV/r-based antiretroviral therapy (ART) for 15 days, which includes lopinavir/ritonavir plus emtricitabine/tenofovir disoproxil fumarate; followed by an nNRTI-based ART, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. | Participants were prescribed to nNRTI-based ART for 15 days, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, followed by an nNRTI-based ART and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. |
| Period Title: Overall Study | ||
| STARTED | 26 | 26 |
| COMPLETED | 25 | 25 |
| NOT COMPLETED | 1 | 1 |
Baseline Characteristics
| Arm/Group Title | LPV/R-based ART | nNRTI-based ART | Total |
|---|---|---|---|
| Arm/Group Description | Participants were prescribed to LPV/r-based antiretroviral therapy (ART) for 15 days, which includes lopinavir/ritonavir plus emtricitabine/tenofovir disoproxil fumarate; followed by an nNRTI-based ART, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. | Participants were prescribed to nNRTI-based ART for 15 days, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, followed by an nNRTI-based ART and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. | Total of all reporting groups |
| Overall Participants | 26 | 26 | 52 |
| Age (years) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [years] |
31
|
31
|
31
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
9
34.6%
|
8
30.8%
|
17
32.7%
|
| Male |
17
65.4%
|
18
69.2%
|
35
67.3%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Black |
26
100%
|
26
100%
|
52
100%
|
| Region of Enrollment (Count of Participants) | |||
| Malawi |
1
3.8%
|
1
3.8%
|
2
3.8%
|
| Uganda |
1
3.8%
|
0
0%
|
1
1.9%
|
| Kenya |
24
92.3%
|
25
96.2%
|
49
94.2%
|
| CD4 cell count (cells/mm^3) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [cells/mm^3] |
360
|
302
|
324
|
| Log10(HIV-1 RNA) (Log10(cp/ml)) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [Log10(cp/ml)] |
5.11
|
5.37
|
5.18
|
| Log10(parasite density) (Log10(parasites/µL)) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [Log10(parasites/µL)] |
2.69
|
2.50
|
2.66
|
Outcome Measures
| Title | Proportion of Participants With Plasmodium Falciparum (Pf) Subclinical Parasitemia (SCP) Clearance |
|---|---|
| Description | Pf SCP clearance defined by polymerase chain reaction (PCR) < 10 parasites/µL on three consecutive occasions within a 24-hour period. If a participant had missing data on day 15, they were considered as not having clearance. |
| Time Frame | Day 15 (3 samples collected, separated by at least 5 hours and all three collected within 24-hours) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary analysis is based on intent-to-treat principles and includes all randomized participants. |
| Arm/Group Title | LPV/R-based ART | nNRTI-based ART |
|---|---|---|
| Arm/Group Description | Participants were prescribed to LPV/r-based antiretroviral therapy (ART) for 15 days, which includes lopinavir/ritonavir plus emtricitabine/tenofovir disoproxil fumarate; followed by an nNRTI-based ART, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. | Participants were prescribed to nNRTI-based ART for 15 days, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, followed by an nNRTI-based ART and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. |
| Measure Participants | 26 | 26 |
| Proportion Cleared |
0.23
0.9%
|
0.27
1%
|
| Proportion Not Cleared |
0.77
3%
|
0.73
2.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LPV/R-based ART, nNRTI-based ART |
|---|---|---|
| Comments | Compare proportions of Pf SCP clearance between treatment arms | |
| Type of Statistical Test | Superiority | |
| Comments | Test used alpha level of 0.05 | |
| Statistical Test of Hypothesis | p-Value | 1.00 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Time to First Pf SCP Clearance |
|---|---|
| Description | Time to clearance is defined by time to first measurement with PCR < 10 parasites/µL, and is evaluated as the point estimate and 95% CI for the day when 50% of participants cleared parasite. |
| Time Frame | From study entry up to day 30 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis only includes participants who received 15 days of treatment, excluding one participant on LPV/r-based ART. One participant on nNRTI-based ART had missing data at all time points. |
| Arm/Group Title | LPV/R-based ART | nNRTI-based ART |
|---|---|---|
| Arm/Group Description | Participants were prescribed to LPV/r-based antiretroviral therapy (ART) for 15 days, which includes lopinavir/ritonavir plus emtricitabine/tenofovir disoproxil fumarate; followed by an nNRTI-based ART, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. | Participants were prescribed to nNRTI-based ART for 15 days, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, followed by an nNRTI-based ART and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. |
| Measure Participants | 25 | 25 |
| Median (95% Confidence Interval) [Days] |
12
|
14
|
| Title | Log10(Pf Parasite Density) |
|---|---|
| Description | Pf parasite density was determined by PCR. If parasite density equals 0, the value is set to 0.01 before log10 transformation. The value 0.01 was chosen based on the smallest observed parasite density value of 0.017. |
| Time Frame | Entry, days 3, 6, 9, 12, 15, 20, 25, 30 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis only includes participants who received 15 days of treatment, excluding one participant on LPV/r-based ART. One participant on nNRTI-based ART had missing data at all time points. Several samples were missing at various time points, as shown by number of participants for each day. |
| Arm/Group Title | LPV/R-based ART | nNRTI-based ART |
|---|---|---|
| Arm/Group Description | Participants were prescribed to LPV/r-based antiretroviral therapy (ART) for 15 days, which includes lopinavir/ritonavir plus emtricitabine/tenofovir disoproxil fumarate; followed by an nNRTI-based ART, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. | Participants were prescribed to nNRTI-based ART for 15 days, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, followed by an nNRTI-based ART and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. |
| Measure Participants | 25 | 25 |
| Entry |
2.48
|
2.09
|
| Day 3 |
1.92
|
1.57
|
| Day 6 |
1.77
|
1.49
|
| Day 9 |
1.65
|
1.63
|
| Day 12 |
1.59
|
1.56
|
| Day 15 |
1.59
|
1.43
|
| Day 20 |
0.65
|
0.67
|
| Day 25 |
0.28
|
0.49
|
| Day 30 |
0.14
|
0.30
|
| Title | Change in log10(Pf Parasite Density) From Entry to Day 30 |
|---|---|
| Description | Change is evaluated as log10(Pf parasite density) at day 30 minus log10(Pf parasite density) at entry. Change is evaluated in four groups: Randomized to nNRTI-based ART with continued Pf SCP at day 15 Randomized to nNRTI-based ART with clearance of Pf SCP at day 15 Randomized to LPV/r-based ART with continued Pf SCP at day 15 Randomized to LPV/r-based ART with clearance of Pf SCP at day 15 |
| Time Frame | Entry, Day 30 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants enrolled with results available at entry and day 30: 3 participants were missing data in 'nNRTI-based ART, not cleared' group. 1 participant was missing data in 'nNRTI-based ART, cleared' group. 1 participant was missing data in 'LPV/r-based ART, not cleared' group. |
| Arm/Group Title | nNRTI-based ART, Not Cleared | nNRTI-based ART, Cleared | LPV/R-based ART, Not Cleared | LPV/R-based ART, Cleared |
|---|---|---|---|---|
| Arm/Group Description | Randomized to nNRTI based ART with continued Pf SCP at day 15 | Randomized to nNRTI based ART with clearance of Pf SCP at day 15 | Randomized to LPV/r based ART with continued Pf SCP at day 15 | Randomized to LPV/r based ART with clearance of Pf SCP at day 15 |
| Measure Participants | 16 | 6 | 19 | 6 |
| Median (Inter-Quartile Range) [log10(parasites/µL)] |
-2.26
|
-1.65
|
-1.82
|
-3.61
|
| Title | Number of Participants With Uncomplicated Clinical Malaria |
|---|---|
| Description | Uncomplicated clinical malaria is defined as the presence of non-severe fever/symptoms and parasitemia without organ complication. |
| Time Frame | From study entry to day 30 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants. |
| Arm/Group Title | LPV/R-based ART | nNRTI-based ART |
|---|---|---|
| Arm/Group Description | Participants were prescribed to LPV/r-based antiretroviral therapy (ART) for 15 days, which includes lopinavir/ritonavir plus emtricitabine/tenofovir disoproxil fumarate; followed by an nNRTI-based ART, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. | Participants were prescribed to nNRTI-based ART for 15 days, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, followed by an nNRTI-based ART and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. |
| Measure Participants | 26 | 26 |
| Count of Participants [Participants] |
2
7.7%
|
1
3.8%
|
| Title | Number of Participants With Detectable Pf Gametocyte Density |
|---|---|
| Description | Number of participants with detectable Pf gametocyte density as determined by PCR. Due to the large number of undetectable results, this outcome was measured as dichotomous. |
| Time Frame | Entry, days 3, 6, 9, 12, 15, 20, 25, 30 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis only includes participants who received 15 days of treatment, excluding one participant on LPV/r-based ART. One other participant on LPV/r-based ART had missing data at all time points. Several samples were missing at various time points, as shown by number of participants for each day. |
| Arm/Group Title | LPV/R-based ART | nNRTI-based ART |
|---|---|---|
| Arm/Group Description | Participants were prescribed to LPV/r-based antiretroviral therapy (ART) for 15 days, which includes lopinavir/ritonavir plus emtricitabine/tenofovir disoproxil fumarate; followed by an nNRTI-based ART, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. | Participants were prescribed to nNRTI-based ART for 15 days, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, followed by an nNRTI-based ART and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. |
| Measure Participants | 24 | 26 |
| Entry |
11
42.3%
|
12
46.2%
|
| Day 3 |
10
38.5%
|
15
57.7%
|
| Day 6 |
9
34.6%
|
12
46.2%
|
| Day 9 |
11
42.3%
|
13
50%
|
| Day 12 |
6
23.1%
|
11
42.3%
|
| Day 15 |
10
38.5%
|
14
53.8%
|
| Day 20 |
11
42.3%
|
14
53.8%
|
| Day 25 |
12
46.2%
|
16
61.5%
|
| Day 30 |
11
42.3%
|
13
50%
|
| Title | Change in log10(Pf Gametocyte Density) From Entry to Day 30 |
|---|---|
| Description | Change in log10(Pf gametocyte density) as evaluated using a Hodges-Lehmann estimate from entry to day 30 is evaluated in two groups: Randomized to nNRTI-based ART with continued Pf SCP at day 15 Randomized to LPV/r-based ART with continued Pf SCP at day 15 Analysis was not conducted in either group with clearance at day 15 due to the small sample size and high number of undetectable samples in both clearance groups at entry and day 30. |
| Time Frame | Entry, Day 30 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants with results available at both entry and day 30 who did not have Pf SCP clearance at day 15. participant was missing from the nNRTI-based ART, not cleared group participants were missing from the LPV/r-based ART, not cleared group |
| Arm/Group Title | nNRTI-based ART, Not Cleared | nNRTI-based ART, Cleared | LPV/R-based ART, Not Cleared | LPV/R-based ART, Cleared |
|---|---|---|---|---|
| Arm/Group Description | Randomized to nNRTI based ART with continued Pf SCP at day 15 | Randomized to nNRTI based ART with clearance of Pf SCP at day 15 | Randomized to LPV/r based ART with continued Pf SCP at day 15 | Randomized to LPV/r based ART with clearance of Pf SCP at day 15 |
| Measure Participants | 18 | 0 | 18 | 0 |
| Number (95% Confidence Interval) [log10(gametocyte/µL)] |
-0.46
|
0.17
|
Adverse Events
| Time Frame | From randomization to study completion at 30 days | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The following adverse event information was collected: Signs and symptoms Grade ≥ 3, and signs and symptoms that led to a change in treatment regardless of grade All laboratory values Grade ≥ 2, and laboratory values that led to a change in treatment regardless of grade All diagnoses identified by ACTG criteria for clinical events and other diseases Deaths Grading performed according to DAIDS AE Grading Table (V1.0). SAEs defined in EAE Manual (V2.0). Refer to Protocol Section 11. | |||
| Arm/Group Title | LPV/R-based ART | nNRTI-based ART | ||
| Arm/Group Description | Participants were prescribed to LPV/r-based antiretroviral therapy (ART) for 15 days, which includes lopinavir/ritonavir plus emtricitabine/tenofovir disoproxil fumarate; followed by an nNRTI-based ART, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. | Participants were prescribed to nNRTI-based ART for 15 days, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, followed by an nNRTI-based ART and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30. | ||
All Cause Mortality |
||||
| LPV/R-based ART | nNRTI-based ART | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/26 (0%) | 0/26 (0%) | ||
Serious Adverse Events |
||||
| LPV/R-based ART | nNRTI-based ART | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/26 (0%) | 0/26 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| LPV/R-based ART | nNRTI-based ART | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/26 (11.5%) | 2/26 (7.7%) | ||
| Gastrointestinal disorders | ||||
| Vomiting | 2/26 (7.7%) | 1/26 (3.8%) | ||
| General disorders | ||||
| Fatigue | 2/26 (7.7%) | 1/26 (3.8%) | ||
| Infections and infestations | ||||
| Plasmodium falciparum infection | 2/26 (7.7%) | 1/26 (3.8%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 2/26 (7.7%) | 1/26 (3.8%) | ||
| Nervous system disorders | ||||
| Headache | 1/26 (3.8%) | 2/26 (7.7%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights
Results Point of Contact
| Name/Title | ACTG Clinicaltrials.gov Coordinator |
|---|---|
| Organization | ACTG Network Coordinating Center, Social and Scientific Systems, Inc. |
| Phone | (301) 628-3313 |
| ACTGCT.Gov@s-3.com |
- ACTG A5297
- 1U01AI068636