- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02787499
Resistance Testing to Improve Management of Virologic Failure in Sub-Saharan Africa (REVAMP)
Resistance Testing Versus Adherence Support for Management of Patients With Virologic Failure on First-Line Antiretroviral Therapy in Sub-Saharan Africa
Study Overview
Status
Intervention / Treatment
Detailed Description
STUDY PROCEDURES FOR PARTICIPANTS RANDOMIZED TO STANDARD OF CARE ARM
A. 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.
B. 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.
C. 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.
D. 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.
E. 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
A. 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.
B. 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.
C. 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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Durban, South Africa
- University of Kwa-Zulu Natal
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Mbarara, Uganda
- Mbarara University of Science and Technology
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
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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.
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Perform drug resistance on enrollment to guide management of virologic failure
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
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Number and percentage of participants achieving virologic suppression.
Virologic resuppression defined as viral load < 200 copies/mL
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9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
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Number and percentage of patients with an undetectable viral load (below limit of detection) at study conclusion.
Viral load < 200 copies/mL
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9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
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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)
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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
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9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
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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)
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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
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9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
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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)
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The number and percentage of patients retained in HIV clinical care at study completion
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9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
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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)
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Odds of 9-month survival.
Number and percentage of participants who survived through the 9-month (then 15-month) study period.
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9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
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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)
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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.
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9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
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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)
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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).
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9 months (end point extended up to 15 months for participants affected by the COVID-19 epidemic)
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Mwebesa Bwana, MBChB MPH, Mbarara University of Science and Technology
- Principal Investigator: Yunus Moosa, MBChB PhD, University of KwaZulu
Publications and helpful links
General 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.
- Siedner 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.
- Reynolds 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.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 2016P000589
- R01AI124718 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
Study Data/Documents
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Individual Participant Data Set
Information comments: Publicly available, de-identified datasets are available on the Harvard Dataverse Platform.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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