Population Effectiveness of Dolutegravir Implementation in Sub-Saharan Africa

HIV-1-infection Clinical Trial

— DISCO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04066036
• Other study ID #: 2019P000898-A
• Secondary ID: K23AI14347021221
• Status: Completed
• Start date: May 14, 2019
• Est. completion date: May 31, 2023

Study information

• Verified date: October 2023
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1000
• Est. completion date: May 31, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Other:
• This is an observational study only.
This is an observational study only.

Locations

Country	Name	City	State
South Africa	Africa Health Research Institute	Somkele	KwaZulu-Natal
Uganda	Mbarara University of Science and Technology	Mbarara

Sponsors (9)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Africa Health Research Institute, Emory University, Harvard Medical School (HMS and HSDM), Mbarara University of Science and Technology, National Institute of Allergy and Infectious Diseases (NIAID), University of KwaZulu, ViiV Healthcare, Wellcome Trust

Countries where clinical trial is conducted

South Africa,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with virologic failure (HIV-1 RNA >= 200 copies/mL)	HIV-1 RNA >= 200 copies/mL	48 weeks
Secondary	Proportion of participants with virologic failure (HIV-1 RNA >= 1,000 copies/mL)	HIV-1 RNA >= 1,000 copies/mL	48 weeks
Secondary	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