HIVREVAMPNCT02787499
Resistance Testing to Improve Management of Virologic Failure in Sub-Saharan Africa
A study testing HIV-1 RNA Resistance Testing in people with HIV and AIDS, run by Massachusetts General Hospital at 2 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- HIV-1 RNA Resistance Testing
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 840 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 8 Dec 2016to 8 Sep 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Resistance Testing Versus Adherence Support for Management of Patients With Virologic Failure on First-Line Antiretroviral Therapy in Sub-Saharan Africa
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.
Read the detailed description
STUDY PROCEDURES FOR PARTICIPANTS RANDOMIZED TO STANDARD OF CARE ARM
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- Being tested
- HIV-1 RNA Resistance Testing
- Keywords
- Drug resistance, Standard of care, sub-saharan africa, antiretroviral therapy, diagnostics, implementation
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HIV-1 RNA Resistance TestingProcedure or surgery
Perform drug resistance on enrollment to guide management of virologic failure
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care | No intervention | 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. |
| HIV-1 RNA Resistance Testing | Experimental | 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. Receives: Procedure: HIV-1 RNA Resistance Testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and Percentage of Patients Achieving Virologic Resuppression
Number and percentage of participants achieving virologic suppression. Virologic resuppression defined as viral load < 200 copies/mL
Measured: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
Secondary outcomes (7)
Number and Percentage of Patients With an Undetectable Viral Load (Below Limit of Detection) at Study Conclusion
Number and percentage of patients with an undetectable viral load (below limit of detection) at study conclusion. Viral load < 200 copies/mL
Measured: 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 on First-line (NNRTI-based) Therapy at Study Conclusion
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
Measured: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
Number and Percentage of Patients With International AIDS Society-defined Drug Resistance Mutations to Their Current Regimen.
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
Measured: 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
Total patient care costs, including diagnostic testing and ART costs for the study duration. These data are reported as median cost and IQR per person by arm.
Measured: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
Number and Percentage of Patients Retained in HIV Clinical Care at Study Completion
The number and percentage of patients retained in HIV clinical care at study completion
Measured: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
Number and Percentage of Participants Survived Through 9-month Study Period
Odds of 9-month survival. Number and percentage of participants who survived through the 9-month (then 15-month) study period.
Measured: 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
Change in health-related quality of life from baseline to 9 months. The scale used is Health-related Quality of Life (HRQoL), where the minimum score is 0 = 'death' and the maximum is 1 = 'perfect' health. We are reporting mean change in HRQoL, so a larger positive value indicates a larger improvement of HRQoL. Two time points used in the calculation were the HRQoL score at the baseline visit and at the final visit at 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic).
Measured: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2016 (estimated)
- Study start8 Dec 2016
- Primary completion8 Sep 2020
- Study completion8 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 840 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Mbarara University of Science and Technology, University of KwaZulu, Emory University, University of Rochester, National Institute of Allergy and Infectious Diseases (NIAID)
- Responsible party
- Principal investigator, Mark Siedner, Massachusetts General Hospital
- Investigators
- Mwebesa Bwana, MBChB MPH, Principal investigator, Mbarara University of Science and TechnologyYunus Moosa, MBChB PhD, Principal investigator, University of KwaZulu
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02787499
- Sponsor's protocol ID
- 2016P000589
- Other IDs
- R01AI124718
- Acronym
- REVAMP
- Status last verified
- Mar 2023
- First submitted
- 26 May 2016
- Last updated
- 21 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Data will be made public and accessible through request after completion of primary analysis.
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.
PubMed 31835974Siedner 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.
PubMed 28720039Siedner MJ, Moosa MS, McCluskey S, Gilbert RF, Pillay S, Aturinda I, Ard K, Muyindike W, Musinguzi N, Masette G, Pillay M, Moodley P, Brijkumar J, Rautenberg T, George G, Gandhi RT, Johnson BA, Sunpath H, Bwana MB, Marconi VC. Resistance Testing for Management of HIV Virologic Failure in Sub-Saharan Africa : An Unblinded Randomized Controlled Trial. Ann Intern Med. 2021 Dec;174(12):1683-1692. doi: 10.7326/M21-2229. Epub 2021 Oct 26.
PubMed 34698502Reynolds Z, McCluskey SM, Moosa MYS, Gilbert RF, Pillay S, Aturinda I, Ard KL, Muyindike W, Musinguzi N, Masette G, Moodley P, Brijkumar J, Rautenberg T, George G, Johnson BA, Gandhi RT, Sunpath H, Marconi VC, Bwana MB, Siedner MJ. Who's slipping through the cracks? A comprehensive individual, clinical and health system characterization of people with virological failure on first-line HIV treatment in Uganda and South Africa. HIV Med. 2022 May;23(5):474-484. doi: 10.1111/hiv.13203. Epub 2021 Nov 9.
PubMed 34755438Rautenberg TA, Ng SK, George G, Moosa MS, McCluskey SM, Gilbert RF, Pillay S, Aturinda I, Ard KL, Muyindike WR, Musinguzi N, Masette G, Pillay M, Moodley P, Brijkumar J, Gandhi RT, Johnson B, Sunpath H, Bwana MB, Marconi VC, Siedner MJ. Determinants of health-related quality of life in people with Human Immunodeficiency Virus, failing first-line treatment in Africa. Health Qual Life Outcomes. 2023 Aug 21;21(1):94. doi: 10.1186/s12955-023-02179-x.
PubMed 37605150
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Resistance Testing Versus Adherence Support for Management of Patients With Virologic Failure on First-Line Antiretroviral Therapy in Sub-Saharan Africa
- ClinicalTrials.gov ID
- NCT02787499
- Acronym / sponsor ID
- REVAMP / 2016P000589
- Keywords
- Drug resistance, Standard of care, sub-saharan africa, antiretroviral therapy, diagnostics, implementation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 840 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Mbarara University of Science and Technology, University of KwaZulu, Emory University, University of Rochester, National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 8 Dec 2016 (actual)
- Primary completion
- 8 Sep 2020 (actual)
- Study completion
- 8 Sep 2020 (actual)
- First posted
- 1 Jun 2016 (estimated)
- Results
- Posted 25 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
STUDY PROCEDURES FOR PARTICIPANTS RANDOMIZED TO STANDARD OF CARE ARM
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- 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
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care | No intervention | –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. |
| HIV-1 RNA Resistance Testing | Experimental | Procedure: HIV-1 RNA Resistance TestingParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HIV-1 RNA Resistance TestingPerform drug resistance on enrollment to guide management of virologic failure | Procedure or surgery | HIV-1 RNA Resistance Testing |
Primary outcome
Number and Percentage of Patients Achieving Virologic Resuppression
Time frame: 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
7 secondary outcomes
Number and Percentage of Patients With an Undetectable Viral Load (Below Limit of Detection) at Study Conclusion
Time frame: 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 on First-line (NNRTI-based) Therapy at Study Conclusion
Time frame: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
Number and Percentage of Patients With International AIDS Society-defined Drug Resistance Mutations to Their Current Regimen.
Time frame: 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
Time frame: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
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)
Number and Percentage of Participants Survived Through 9-month Study Period
Time frame: 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
Time frame: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31835974Rautenberg 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.
- Background: PubMed 28720039Siedner 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.
- Results publication: PubMed 34698502Siedner MJ, Moosa MS, McCluskey S, Gilbert RF, Pillay S, Aturinda I, Ard K, Muyindike W, Musinguzi N, Masette G, Pillay M, Moodley P, Brijkumar J, Rautenberg T, George G, Gandhi RT, Johnson BA, Sunpath H, Bwana MB, Marconi VC. Resistance Testing for Management of HIV Virologic Failure in Sub-Saharan Africa : An Unblinded Randomized Controlled Trial. Ann Intern Med. 2021 Dec;174(12):1683-1692. doi: 10.7326/M21-2229. Epub 2021 Oct 26.
- Results publication: PubMed 34755438Reynolds Z, McCluskey SM, Moosa MYS, Gilbert RF, Pillay S, Aturinda I, Ard KL, Muyindike W, Musinguzi N, Masette G, Moodley P, Brijkumar J, Rautenberg T, George G, Johnson BA, Gandhi RT, Sunpath H, Marconi VC, Bwana MB, Siedner MJ. Who's slipping through the cracks? A comprehensive individual, clinical and health system characterization of people with virological failure on first-line HIV treatment in Uganda and South Africa. HIV Med. 2022 May;23(5):474-484. doi: 10.1111/hiv.13203. Epub 2021 Nov 9.
- Derived from this study: PubMed 37605150Rautenberg TA, Ng SK, George G, Moosa MS, McCluskey SM, Gilbert RF, Pillay S, Aturinda I, Ard KL, Muyindike WR, Musinguzi N, Masette G, Pillay M, Moodley P, Brijkumar J, Gandhi RT, Johnson B, Sunpath H, Bwana MB, Marconi VC, Siedner MJ. Determinants of health-related quality of life in people with Human Immunodeficiency Virus, failing first-line treatment in Africa. Health Qual Life Outcomes. 2023 Aug 21;21(1):94. doi: 10.1186/s12955-023-02179-x.
- De-identified Participant Data SetLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data will be made public and accessible through request after completion of primary analysis.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mwebesa Bwana, MBChB MPH principal investigator
Mbarara University of Science and Technology
Yunus Moosa, MBChB PhD principal investigator
University of KwaZulu
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HIV-1 RNA Resistance Testing in people with HIV and AIDS, run by Massachusetts General Hospital at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Africa, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and Percentage of Patients Achieving Virologic Resuppression (time frame: 9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02787499, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2023.