Population Effectiveness of Dolutegravir Implementation in Sub-Saharan Africa (DISCO)
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|ClinicalTrials.gov Identifier: NCT04066036|
Recruitment Status : Recruiting
First Posted : August 22, 2019
Last Update Posted : August 28, 2019
|Condition or disease||Intervention/treatment|
|HIV-1-infection||Other: This is an observational study only.|
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.
|Study Type :||Observational|
|Estimated Enrollment :||1000 participants|
|Official Title:||Population Effectiveness of Dolutegravir Implementation in Sub-Saharan Africa: A Prospective Observational Cohort Study|
|Actual Study Start Date :||May 14, 2019|
|Estimated Primary Completion Date :||October 1, 2021|
|Estimated Study Completion Date :||October 1, 2021|
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.
This is an observational study only.
- Proportion of participants with virologic failure (HIV-1 RNA >= 200 copies/mL) [ Time Frame: 48 weeks ]HIV-1 RNA >= 200 copies/mL
- Proportion of participants with virologic failure (HIV-1 RNA >= 1,000 copies/mL) [ Time Frame: 48 weeks ]HIV-1 RNA >= 1,000 copies/mL
- Proportion of participants with HIV drug resistance [ Time Frame: 24 and 48 weeks ]Proportion of participants with International AIDS Society-defined drug resistance mutations to their current regimen
Biospecimen Retention: Samples With DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04066036
|Contact: Suzanne M McCluskey, MDemail@example.com|
|Africa Health Research Institute||Not yet recruiting|
|Somkele, KwaZulu-Natal, South Africa|
|Contact: Mark J Siedner, MD, MPH firstname.lastname@example.org|
|Mbarara University of Science and Technology||Recruiting|
|Contact: Mwebesa B Bwana, MBChB email@example.com|
|Contact: Winnie Muyindike, MBChB firstname.lastname@example.org|
|Principal Investigator: Mwebesa B Bwana, MBChB|
|Sub-Investigator: Winnie Muyindike, MBChB|
|Principal Investigator:||Suzanne M McCluskey, MD||Massachusetts General Hospital|
|Principal Investigator:||Mark J Siedner, MD, MPH||Massachusetts General Hospital, Africa Health Research Institute|