Population Effectiveness of Dolutegravir Implementation in Sub-Saharan Africa (DISCO)

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

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.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Other: This is an observational study only.

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 1000

Contacts and Locations

• Study Contact: Name: Suzanne M McCluskey, MD; Phone Number: 617-726-9488; Email: smccluskey@mgh.harvard.edu

Study Locations

• South Africa
  • KwaZulu-Natal
    • Somkele, KwaZulu-Natal, South Africa
      • Africa Health Research Institute
• Uganda
  • Mbarara, Uganda
    • Mbarara University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will enroll a total of 1,000 individuals from Uganda and South Africa, who are currently enrolled in care at one of the study clinics who have been taking NNRTI-based ART for a minimum of six months, and who are switching to TLD. 500 participants will be recruited from Uganda, and 500 will be recruited from South Africa.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study Population; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Harvard Medical School (HMS and HSDM); National Institute of Allergy and Infectious Diseases (NIAID); Emory University; Wellcome Trust; ViiV Healthcare; Mbarara University of Science and Technology; University of KwaZulu; Africa Health Research Institute
• Investigators: Principal Investigator: Suzanne M McCluskey, MD, Massachusetts General Hospital; Principal Investigator: Mark J Siedner, MD, MPH, Massachusetts General Hospital, Africa Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2019
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: August 21, 2019
• First Submitted That Met QC Criteria: August 21, 2019
• First Posted (Actual): August 22, 2019

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Anti-HIV Agents; HIV-1; South Africa; Sub-Saharan Africa; Uganda; Medication Adherence; HIV Integrase Inhibitors; Virologic Failure; Viral Drug Resistance
• Other Study ID Numbers: 2019P000898-A; K23AI143470 (U.S. NIH Grant/Contract); 212215 (Other Grant/Funding Number: ViiV Healthcare); WT108082AIA (Other Grant/Funding Number: Wellcome Trust)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be made public and accessible through request after completion of the primary analysis.
• IPD Sharing Time Frame: After completion of the primary analysis
• IPD Sharing Access Criteria: De-identified data and supporting information will be made available upon request after agreement among the principal investigators, and based on what is allowable in the study informed consent documents.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No