Resistance Testing Versus Adherence Support for Management of Patients With Virologic Failure on First-Line Antiretroviral Therapy in Sub-Saharan Africa
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 840
- 试验地点
- 2
- 主要终点
- Number and Percentage of Patients Achieving Virologic Resuppression
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Number and Percentage of Patients Achieving Virologic Resuppression
时间窗: 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
次要结局
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
研究者
Mark Siedner
Assistant Professor of Medicine
Massachusetts General Hospital