REVAMP: Resistance Testing to Improve Management of Virologic Failure in Sub-Saharan Africa

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02787499
• Collaborator: Mbarara University of Science and Technology (Other), University of KwaZulu (Other), Emory University (Other), University of Rochester (Other), National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 840
• Locations: 2
• Arms: 2
• Actual Duration (Months): 45
• Patients Per Site: 420
• Patients Per Site Per Month: 9.3

Study Details

Study Description

Brief Summary

The study design is an open-label, randomized controlled trial. The study will be conducted at study sites in Uganda and South Africa. The study population will include HIV-infected patients on first-line antiretroviral therapy with a recent viral load >1,000 copies/milliliter (or dried blood spot viral load >1,000 copies/milliliter). Eligible participants will be randomized to the WHO-based standard of care for management of virologic failure or immediate resistance testing to guide ART regimen decisions. The primary outcome of interest will be viral suppression (<200 copies/mL) at 9 months after study enrollment, and will be assessed using an intention to treat analysis, where missing or absent results will be considered failures. Secondary outcomes of interest will be viral suppression below the limit of assay detection, viral suppression on continuation of first-line (non-nucleoside reverse transcriptase inhibitor [NNRTI]-based) therapy, drug resistance at study conclusion, and mortality, among others. The overarching goal of this study is to determine whether addition of routine resistance testing, to guide management of virologic failure and sustain the successful completion of the HIV continuum of care, improves clinical outcomes and reduces costs for patients with virologic failure on first-line therapy in sub-Saharan Africa.

Condition or Disease	Intervention/Treatment	Phase
HIV; AIDS	Procedure: HIV-1 RNA Resistance Testing	N/A

Detailed Description

STUDY PROCEDURES FOR PARTICIPANTS RANDOMIZED TO STANDARD OF CARE ARM

1. Visit 1-SOC: Baseline Visit for Standard of Care Participants

At Study Visit 1, participants randomized to the SOC will complete the baseline questionnaire to collect sociodemographic, HIV clinical and treatment history, self-reported ART medication adherence, quality of life, and resource allocation data. Study staff will review participant records to collect data on clinic initiation start date, opportunistic infection history, ART initiation date, ART regimen history, CD4 count and viral load result histories. A single 10cc blood specimen will be drawn for storage for future testing for viral load, resistance testing, and drug therapeutic monitoring. Upon completion of the baseline questionnaire, participants will be referred to clinic counselors who will conduct adherence support counseling as per standard clinical procedures. A follow-up study visit will be scheduled 3 months from the baseline date (or at 1 month for pregnant participants only). Any interim clinical visits that are indicated by the clinic staff will be maintained. The participant will be instructed to continue their current ART regimen until at least the next clinical visit.

1. Visit 2A-SOC: Repeat Viral Load Testing Visit

At Study Visit 2A, participants in the SOC arm will undergo blood collection for viral load testing in keeping with WHO guidelines. An additional tube 10cc tube will be drawn for storage for future analyses. A study questionnaire will be administered to assess self-reported ART medication adherence. No other procedures are scheduled at this visit. Participants will be notified that study staff will contact them as soon as their results are available, to request return to clinic for further management. The participant will be instructed to continue their current ART regimen until at least the next clinical visit. As soon as the viral load result is available, study participants will be contacted and requested to return to clinic for review. If the viral load is indeterminate or not completed for any reason, study staff will request that the participant return for a repeat viral load test.

1. Visit 2B-SOC: Viral Load Testing Results and Therapeutic Management

At Study Visit 2B, study clinicians will review the viral load result. Participants with a viral load ≤ 1,000 copies/mL will continue their first-line (NNRTI-based) ART regimen without change. Participants with a viral load >1,000 copies/mL will change ART regimen to a second-line, protease inhibitor (PI)-based or, if available, integrase inhibitor (II)-based therapy. Clinicians will also be encouraged to change the nucleos(t)ide reverse transcriptase component of the regimen (for example, changing from zidovudine to tenofovir), based on prior exposures, as well as WHO and national guidelines. All regimen decisions will be made by the study clinician, in cooperation with clinic staff at the study sites. In the case of complex management issues, the site principal investigators (Dr. Bosco Bwana in Mbarara and Dr. Yunus Moosa in Durban) will be contacted to offer input. At the conclusion of Visit 2B-SOC, participants in the SOC arm will be scheduled for a final study visit approximately 6 months later. A final visit at 6 months is chosen to allow ample time for drug suppression for participants with detectable viral load at this 3-month visit. Non-study clinical visits for routine clinical care will continue in the interim as determined and scheduled by clinic staff.

1. Visit 3: Outcome Assessment

At Study Visit 3, participants will undergo repeat blood testing for plasma viral load and, if the viral load is detectable, reflex resistance testing will be performed. An additional 10cc tube will be drawn for storage for future testing. A study questionnaire will be administered to assess resource allocation, ART medication adherence, and quality of life. Study staff will review participant records to update interim CD4 count, viral load, and ART regimen data. Results of viral load and resistance testing from this visit will be immediately made available to clinic staff for further patient management. At the conclusion of Visit 3, study procedures will be complete.

1. Missing and Late Appointments

If study participants do not return for study visits, study staff will call them to encourage return to clinic for continuation or completion of procedures. For participants who do not return within 7 days of a scheduled visit and unreachable by phone, a study staff member will attempt to track them at home using a standardized lost-to-follow-up form and procedures developed and used successfully both for program and clinical care in Mbarara for over 10 years. If participants are located, study staff will encourage them to return to clinic to complete procedures and/or conduct the blood draw and questionnaire in in the field if the participant agrees.

STUDY PROCEDURES FOR PARTICIPANTS RANDOMIZED TO RESISTANCE TESTING ARM

1. Visit 1-RT: Baseline Visit for Resistance Testing Participants

At Study Visit 1, participants randomized to the RT will complete the baseline questionnaire to collect sociodemographic, HIV clinical and treatment history, self-reported ART medication adherence, quality of life, and resource allocation data. Study staff will review participant records to collect data on clinic initiation start date, opportunistic infection history, ART initiation date, ART regimen history, CD4 count and viral load result histories. Upon completion of the baseline questionnaire, participants will undergo phlebotomy for resistance testing. Participants will be notified that study staff will contact them as soon as their results are available, to request return to clinic for further management. Upon completion of the study procedures, participants will be referred to clinic counselors who will conduct adherence support counseling as per standard clinical procedures. The participant will be instructed to continue their current ART regimen until at least the next clinical visit. As soon as the resistance test result is available, study participants will be contacted by phone and requested to return to clinic for review.

1. Visit 2-RT: Resistance Testing Results and Therapeutic Management

At Study Visit 2-RT, study clinicians will review the resistance testing result. A study HIV-1 RNA drug resistance interpretation guide will be used to help guide decision-making. Participants without significant drug resistance, as determined by the study clinician in consultation with the resistance interpretation guide will continue their first-line (NNRTI-based) ART regimen without change. Participants with therapeutic drug resistance will change ART regimen to a second-line, protease inhibitor (PI)-based or, if available, integrase inhibitor (II)-based therapy. Clinicians will also be encouraged to change the nucleos(t)ide reverse transcriptase component of the regimen (for example, changing from zidovudine to tenofovir). All regimen decisions will be made by the study clinician, in cooperation with clinic staff at the study sites. In the case of complex management issues, the site principal investigators (Dr. Bosco Bwana in Mbarara and Dr. Yunus Moosa in Durban) will be contacted to offer input. At the conclusion of Visit 2-RT, participants will be scheduled for a final study visit approximately 9 months from the time of enrollment. A final visit 9 months later is chosen to match the approximate 9-month study duration for participants in the SOC arm. Non-study clinical visits for routine clinical care will continue in the interim as determined and scheduled by clinic staff.

1. Visit 3: Outcome Assessment

At Study Visit 3, participants will undergo repeat blood testing for plasma viral load and, if the viral load is detectable, reflex resistance testing will be performed. An additional 10cc tube will be drawn for storage for future testing for viral load, resistance testing, and drug therapeutic monitoring. A study questionnaire will be administered to assess resource allocation and quality of life. Study staff will review participant records to update interim CD4 count, viral load, and ART regimen data. Results of viral load and resistance testing from this visit will be immediately made available to clinic staff for further patient management. At the conclusion of Visit 3, study procedures will be complete.

Study Design

• Study Type: Interventional
• Actual Enrollment: 840 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Resistance Testing Versus Adherence Support for Management of Patients With Virologic Failure on First-Line Antiretroviral Therapy in Sub-Saharan Africa
• Actual Study Start Date: Dec 8, 2016
• Actual Primary Completion Date: Sep 8, 2020
• Actual Study Completion Date: Sep 8, 2020

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Standard of Care Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load <1,000 copies/mL at repeat testing will be retained on first-line therapy.
Experimental: HIV-1 RNA Resistance Testing Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing.	Procedure: HIV-1 RNA Resistance Testing; Perform drug resistance on enrollment to guide management of virologic failure

Outcome Measures

Primary Outcome Measures

1. Number and Percentage of Patients Achieving Virologic Resuppression [9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)]

   Number and percentage of participants achieving virologic suppression. Virologic resuppression defined as viral load < 200 copies/mL

Secondary Outcome Measures

1. Number and Percentage of Patients With an Undetectable Viral Load (Below Limit of Detection) at Study Conclusion [9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)]

   Number and percentage of patients with an undetectable viral load (below limit of detection) at study conclusion. Viral load < 200 copies/mL

2. Number and Percentage of Patients With an Undetectable Viral Load on First-line (NNRTI-based) Therapy at Study Conclusion [9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)]

   The number and percentage of patients with an undetectable viral load on first-line (NNRTI-based) therapy at study conclusion. Viral load < 200 copies/mL

3. Number and Percentage of Patients With International AIDS Society-defined Drug Resistance Mutations to Their Current Regimen. [9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)]

   Proportion of patients with International AIDS Society-defined drug resistance mutations to their current regimen. As part of this analysis, we will also evaluate for minority drug resistance

4. Total Patient Care Costs, Including Diagnostic Testing and ART Costs for the Study Duration [9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)]

   Total patient care costs, including diagnostic testing and ART costs for the study duration. These data will be reported once their analysis is completed by a health economist.

5. Number and Percentage of Patients Retained in HIV Clinical Care at Study Completion [9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)]

   The number and percentage of patients retained in HIV clinical care at study completion

6. Number and Percentage of Participants Survived Through 9-month Study Period [9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)]

   Odds of 9-month survival. Number and percentage of participants who survived through the 9-month (then 15-month) study period.

7. Change in Health-related Quality of Life From Baseline to 9 Months [9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)]

   Change in health-related quality of life from baseline to 9 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• In care at a public HIV clinic within a PEPFAR-focus sub-Saharan African country (South Africa or Uganda) and living within 100 kilometers of the clinic

• Age ≥ 18 years at the time of enrollment

• Currently prescribed first-line (non-nucleoside reverse transcriptase inhibitor [NNRTI]-based) ART for at least 5 months. Switches within first line regimens, including NNRTI and nucleos(t)ide backbone changes are allowed.

• Detectable plasma viral load > 1,000 copies/mL or dried blood spot viral load > 1,000 copies/mL within 90 days of enrollment

Exclusion Criteria:

• Known prior drug resistance

• Prior exposure to PI-based ART

• Current clinical indication to start PI-based ART

• Not planning to remain in the clinic catchment area for the next nine months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Kwa-Zulu Natal	Durban		South Africa
2	Mbarara University of Science and Technology	Mbarara		Uganda

Sponsors and Collaborators

• Massachusetts General Hospital
• Mbarara University of Science and Technology
• University of KwaZulu
• Emory University
• University of Rochester
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Mwebesa Bwana, MBChB MPH, Mbarara University of Science and Technology
• Principal Investigator: Yunus Moosa, MBChB PhD, University of KwaZulu

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 14, 2020
• Informed Consent Form - Jan 19, 2018

More Information

Additional Information:

• De-identified Participant Data Set

Publications

• Rautenberg TA, George G, Bwana MB, Moosa MS, Pillay S, McCluskey SM, Aturinda I, Ard K, Muyindike W, Moodley P, Brijkumar J, Johnson BA, Gandhi RT, Sunpath H, Marconi VC, Siedner MJ. Comparative analyses of published cost effectiveness models highlight critical considerations which are useful to inform development of new models. J Med Econ. 2020 Mar;23(3):221-227. doi: 10.1080/13696998.2019.1705314. Epub 2020 Jan 11.
• Siedner MJ, Bwana MB, Moosa MS, Paul M, Pillay S, McCluskey S, Aturinda I, Ard K, Muyindike W, Moodley P, Brijkumar J, Rautenberg T, George G, Johnson B, Gandhi RT, Sunpath H, Marconi VC. The REVAMP trial to evaluate HIV resistance testing in sub-Saharan Africa: a case study in clinical trial design in resource limited settings to optimize effectiveness and cost effectiveness estimates. HIV Clin Trials. 2017 Jul;18(4):149-155. doi: 10.1080/15284336.2017.1349028. Epub 2017 Jul 18. Review.

• Responsible Party: Mark Siedner, Assistant Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02787499
• Other Study ID Numbers: 2016P000589; R01AI124718
• First Posted: Jun 1, 2016
• Last Update Posted: Apr 25, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Mark Siedner, Assistant Professor of Medicine, Massachusetts General Hospital: Drug resistance; Standard of care; sub-saharan africa; antiretroviral therapy; diagnostics; implementation

Study Results

Participant Flow

Arm/Group Title	Standard of Care	HIV-1 RNA Resistance Testing
Arm/Group Description	Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load <1,000 copies/mL at repeat testing will be retained on first-line therapy.	Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing. HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
Period Title: Overall Study
STARTED	423	417
COMPLETED	423	417
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Standard of Care	HIV-1 RNA Resistance Testing	Total
Arm/Group Description	Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load <1,000 copies/mL at repeat testing will be retained on first-line therapy.	Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing. HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure	Total of all reporting groups
Overall Participants	423	417	840
Age (Count of Participants)
<=18 years	4 0.9%	2 0.5%	6 0.7%
Between 18 and 65 years	415 98.1%	412 98.8%	827 98.5%
>=65 years	4 0.9%	3 0.7%	7 0.8%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	37	37	37
Sex: Female, Male (Count of Participants)
Female	221 52.2%	209 50.1%	430 51.2%
Male	202 47.8%	208 49.9%	410 48.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	423 100%	417 100%	840 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Uganda	210 49.6%	210 50.4%	420 50%
South Africa	213 50.4%	207 49.6%	420 50%
Median Antiretroviral therapy (ART) duration (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	3.5	3.0	3.2
Country (Count of Participants)
Uganda	210 49.6%	210 50.4%	420 50%
South Africa	213 50.4%	207 49.6%	420 50%
Pregnancy (Count of Participants)
Pregnant at enrollment	7 1.7%	6 1.4%	13 1.5%
Not pregnant at enrollment	416 98.3%	411 98.6%	827 98.5%
Median CD4 count (x 10^9 cells/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [x 10^9 cells/L]	0.303	0.259	0.281
ART regimen (Count of Participants)
TDF-3(F)TC-EFV	311 73.5%	295 70.7%	606 72.1%
AZT-3TC-NVP	60 14.2%	58 13.9%	118 14%
Other	52 12.3%	64 15.3%	116 13.8%
Self-reported treatment adherence at enrollment (Count of Participants)
<100% in prior 30 d	297 70.2%	295 70.7%	592 70.5%
100% in prior 30 d	126 29.8%	122 29.3%	248 29.5%

Outcome Measures

1. Primary Outcome

Title	Number and Percentage of Patients Achieving Virologic Resuppression
Description	Number and percentage of participants achieving virologic suppression. Virologic resuppression defined as viral load < 200 copies/mL
Time Frame	9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care	HIV-1 RNA Resistance Testing
Arm/Group Description	Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load <1,000 copies/mL at repeat testing will be retained on first-line therapy.	Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing. HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
Measure Participants	423	417
Count of Participants [Participants]	256 60.5%	263 63.1%

2. Secondary Outcome

Title	Number and Percentage of Patients With an Undetectable Viral Load (Below Limit of Detection) at Study Conclusion
Description	Number and percentage of patients with an undetectable viral load (below limit of detection) at study conclusion. Viral load < 200 copies/mL
Time Frame	9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care	HIV-1 RNA Resistance Testing
Arm/Group Description	Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load <1,000 copies/mL at repeat testing will be retained on first-line therapy.	Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing. HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
Measure Participants	423	417
Count of Participants [Participants]	193 45.6%	202 48.4%

3. Secondary Outcome

Title	Number and Percentage of Patients With an Undetectable Viral Load on First-line (NNRTI-based) Therapy at Study Conclusion
Description	The number and percentage of patients with an undetectable viral load on first-line (NNRTI-based) therapy at study conclusion. Viral load < 200 copies/mL
Time Frame	9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care	HIV-1 RNA Resistance Testing
Arm/Group Description	Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load <1,000 copies/mL at repeat testing will be retained on first-line therapy.	Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing. HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
Measure Participants	423	417
Count of Participants [Participants]	81 19.1%	62 14.9%

4. Secondary Outcome

Title	Number and Percentage of Patients With International AIDS Society-defined Drug Resistance Mutations to Their Current Regimen.
Description	Proportion of patients with International AIDS Society-defined drug resistance mutations to their current regimen. As part of this analysis, we will also evaluate for minority drug resistance
Time Frame	9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care	HIV-1 RNA Resistance Testing
Arm/Group Description	Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load <1,000 copies/mL at repeat testing will be retained on first-line therapy.	Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing. HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
Measure Participants	103	82
Count of Participants [Participants]	25 5.9%	34 8.2%

5. Secondary Outcome

Title	Total Patient Care Costs, Including Diagnostic Testing and ART Costs for the Study Duration
Description	Total patient care costs, including diagnostic testing and ART costs for the study duration. These data will be reported once their analysis is completed by a health economist.
Time Frame	9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Number and Percentage of Patients Retained in HIV Clinical Care at Study Completion
Description	The number and percentage of patients retained in HIV clinical care at study completion
Time Frame	9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care	HIV-1 RNA Resistance Testing
Arm/Group Description	Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load <1,000 copies/mL at repeat testing will be retained on first-line therapy.	Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing. HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
Measure Participants	423	417
Count of Participants [Participants]	403 95.3%	394 94.5%

7. Secondary Outcome

Title	Number and Percentage of Participants Survived Through 9-month Study Period
Description	Odds of 9-month survival. Number and percentage of participants who survived through the 9-month (then 15-month) study period.
Time Frame	9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care	HIV-1 RNA Resistance Testing
Arm/Group Description	Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load <1,000 copies/mL at repeat testing will be retained on first-line therapy.	Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing. HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
Measure Participants	423	417
Count of Participants [Participants]	415 98.1%	403 96.6%

8. Secondary Outcome

Title	Change in Health-related Quality of Life From Baseline to 9 Months
Description	Change in health-related quality of life from baseline to 9 months.
Time Frame	9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
Arm/Group Title	Standard of Care		HIV-1 RNA Resistance Testing
Arm/Group Description	Follows the 2013 World Health Organization (WHO) HIV treatment guidelines. Study participants will receive adherence support and return for a repeat viral load test in 3 months (or in 1 month for pregnant participants). Treatment failure will be defined by two consecutive viral load measurements greater than 1,000 copies/mL. Participants who meet this criteria will be switched to second-line therapy. Those with a viral load <1,000 copies/mL at repeat testing will be retained on first-line therapy.		Participants will receive HIV-1 RNA drug resistance testing at study enrollment. ART treatment regimen decisions will be determined based on the results of resistance testing. HIV-1 RNA Resistance Testing: Perform drug resistance on enrollment to guide management of virologic failure
All Cause Mortality
	Standard of Care		HIV-1 RNA Resistance Testing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/423 (1.9%)		14/417 (3.4%)
Serious Adverse Events
	Standard of Care		HIV-1 RNA Resistance Testing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/423 (0%)		0/417 (0%)
Other (Not Including Serious) Adverse Events
	Standard of Care		HIV-1 RNA Resistance Testing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/423 (0%)		0/417 (0%)

Limitations/Caveats

The study underwent a single major protocol change in 2020, when the study window was extended for participants who were actively enrolled in the trial but unable to return to the clinic for their outcome assessment while COVID-19 transportation restrictions were imposed in both countries (24 March 2020 in Uganda and 27 March 2020 in South Africa.

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.