Population Effectiveness of Dolutegravir Implementation in Sub-Saharan Africa

Study Overview
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Brief Summary
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This is a prospective observational cohort study enrolling participants in South Africa and Uganda who are prescribed an HIV treatment regimen containing lamivudine, tenofovir, and dolutegravir, which is known as TLD. We hope to better understand how effective TLD will be in sub-Saharan Africa. If treatment failure occurs, we seek to understand the possible reasons, including drug resistance and adherence challenges.

Detailed Description
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This study is a prospective observational cohort study at three government-supported HIV clinics in rural South Africa and Uganda. We will enroll 1,000 adults living with HIV who are switched from first-line antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) to TLD. We will follow participants for one year with study visits at enrollment, 24 weeks, and 48 weeks. Study procedures include interviews, body measurements, chart review, and collection of blood and urine specimens for retrospective testing, including viral load, drug resistance testing, antiretroviral drug level testing, and tests to evaluate the effects of TLD on renal, liver, metabolic, and other organ function. Aim 1: To determine the contributions of resistance prior to switch to TLD from a NNRTI-based regimen to risk of treatment failure after six and twelve months on TLD. Hypothesis: People living with HIV who experience virologic failure on TLD will have increased odds of NRTI mutations prior to TLD exposure, compared to controls with virologic suppression. Aim 2: Explore pharmacologic measures of adherence to distinguish virologic failure on TLD due to suboptimal adherence versus resistance using 2a) urine tenofovir (TFV) levels and 2b) tenofovir diphosphate (TFV-DP) in dried blood spots (DBS). Hypothesis: Absence of TFV in urine and TFV-DP concentrations in DBS will distinguish ART failure with versus without resistance.

Official Title
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Population Effectiveness of Dolutegravir Implementation in Sub-Saharan Africa: A Prospective Observational Cohort Study

Conditions
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HIV-1-infection

Intervention / Treatment
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* Other: This is an observational study only.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years HIV-positive and in care at one of the study clinics Current use of NNRTI-based, first-line ART for a minimum of 6 months Prescribed change to TLD by clinic staff Residing within 100 kilometers of the treatment clinic without plans to change permanent residence in the next 48 weeks Consents to participation Exclusion Criteria: There are no specific exclusion criteria. Both men and women will be theoretically eligible. We note that decision to use TLD in patients at the recruitment clinic will be made by clinic staff, and referral for study procedures will not be made until after this decision is made. We also note that, as of the time of this protocol draft, TLD use might be limited to men, women of non-child bearing ages, and women confirmed to be on contraception. This study will follow both national guidelines and clinician discretion about use of TLD in the clinic population.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study Population<br>The study will enroll a total of 1,000 ART-experienced participants from the study sites in Uganda and South Africa who are being transitioned to TLD from non-nucleoside reverse transcriptase-based antiretroviral therapy. | Other: This is an observational study only.<br>* This is an observational study only.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with virologic failure (HIV-1 RNA >= 200 copies/mL) | HIV-1 RNA >= 200 copies/mL | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with virologic failure (HIV-1 RNA >= 1,000 copies/mL) | HIV-1 RNA >= 1,000 copies/mL | 48 weeks | 
| Proportion of participants with HIV drug resistance | Proportion of participants with International AIDS Society-defined drug resistance mutations to their current regimen | 24 and 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV Integrase Inhibitors, Sub-Saharan Africa, Anti-HIV Agents, Medication Adherence, Virologic Failure, Viral Drug Resistance, South Africa, Uganda, HIV-1