A Randomized Clinical Trial to Evaluate Solutions for the Management of Virologic Failure on TLD in Sub-Saharan Africa (RESOLVE)

March 17, 2026 updated by: Suzanne McCluskey, Massachusetts General Hospital

A Randomized Clinical Trial to Evaluate Solutions for the Management of Virologic Failure for Individuals on Tenofovir, Lamivudine, and Dolutegravir (TLD) in Sub-Saharan Africa

The RESOLVE trial is an open, parallel arm, randomized clinical trial which aims to determine the optimal strategy for management of virologic failure on antiretroviral therapy (ART) with tenofovir, lamivudine, and dolutegravir (TLD) in sub-Saharan Africa. The primary outcome of interest will be viral suppression to <50 copies/mL at 48 weeks using the FDA snapshot definition. The study will be conducted in Uganda and South Africa.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The RESOLVE trial is an open, parallel arm, randomized clinical trial which will be conducted at public-sector HIV clinics in Uganda and South Africa. We will enroll individuals with HIV age 15 and above who have had two HIV-1 RNA viral load results >1,000 copies/mL while on TLD and who have been on TLD for at least 12 months. Participants will be randomized using an equal allocation ratio of 1:1:1 across three study arms: a) Standard of Care (regimen guided by genotypic resistance tests and care as per guidelines in Uganda; and with regimen selection and possible genotypic resistance testing (GRT) and care as per guidelines in South Africa), 2) Individualized Care with regimen choice based on results of genotypic resistance tests and urine tenofovir adherence assays, or 3) Immediate Switch to PI-based second-line ART. Randomization will be stratified by clinic, prior exposure to non-nucleoside reverse transcriptase inhibitors, and virologic failure history. We will follow participants for one year with study visits at enrollment, Week 24, and Week 48. The primary outcome of interest will be viral suppression to <50 copies/mL at 48 weeks using the FDA snapshot definition.

Study Type

Interventional

Enrollment (Estimated)

648

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • South Africa
      • Durban, South Africa
        • Recruiting
        • RK Khan Hospital Clinic
        • Contact:
          • Richard Lessells
        • Principal Investigator:
          • Richard Lessells
        • Sub-Investigator:
          • Mahomed Y Moosa
  • Uganda
      • Mbarara, Uganda
        • Recruiting
        • Mbarara City Clinic
        • Contact:
          • Winnie Muyindike
        • Principal Investigator:
          • Winnie Muyindike
      • Mbarara, Uganda
        • Recruiting
        • Mbarara Regional Referral Hospital Immune Suppression Syndrome Clinic
        • Contact:
          • Winnie Muyindike
        • Principal Investigator:
          • Winnie Muyindike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 15 years and above
  • Enrolled in HIV care at one of the study clinics
  • History of two HIV-1 RNA viral load measurements >1,000 copies/mL while on TLD
  • On TLD for at least 12 months

  • Lives within 100 kilometers of study clinic

    • Pregnant women are eligible for enrollment.

Exclusion Criteria:

  • Plans to transfer out of the clinic within the next 48 weeks
  • Plans to move out of the study catchment area within the next 48 weeks
  • As determined by chart review, we will exclude those with known virologic failure on protease inhibitors or exposure to integrase strand transfer inhibitors other than dolutegravir.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Individualized Care
Participants will undergo routine EAC, point-of-care urine tenofovir (TFV) testing, and genotypic resistance testing (GRT) at enrollment. Participants will return when GRT results are available for a treatment decision. Side effects and tolerance will also be assessed. All information will be used to make an optimal treatment recommendation with participant input. Participants will have an additional study visit at Week 24 and will continue to have routine care visits, adherence counseling by the clinic, and viral load monitoring at intervals determined by the clinic per national guidelines. Participants will undergo plasma HIV-1 RNA viral load testing at Week 48.
Other: Individualized Care treatment strategy
Management of virologic failure on TLD using the Individualized Care strategy
Experimental: Immediate Switch
Participants will undergo routine EAC and a switch from TLD to PI-based second-line ART at the enrollment visit (Week 0). Participants will have an additional study visit at Week 24. Participants will continue to have routine care visits and viral load monitoring at intervals determined by the clinic per national guidelines. At study completion, participants will undergo plasma HIV-1 RNA viral load testing at Week 48.
Other: Immediate Switch
Management of virologic failure on TLD using the Immediate Switch strategy
Experimental: Standard of Care

In Uganda, participants will be managed per Ministry of Health (MOH) guidelines. GRT is performed by MOH for individuals with virologic failure on TLD. Participants will continue enhanced adherence counseling (EAC) and TLD while awaiting the GRT result. Treatment decision will be made by the regional switch committee when GRT results return. There will be a Week 24 visit for specimen collection.

In South Africa, participants will be managed per Department of Health (DOH) guidelines. Some individuals will be eligible for GRT (performed by DOH) based on ART duration and adherence per DOH guidelines. Treatment decision will be made by the clinic when GRT results return. Individuals who are ineligible for GRT will undergo EAC and continue on TLD. At Weeks 24, participants will undergo plasma HIV-1 RNA viral load testing. Results will be returned to the clinic team for patient management per DOH guidelines.

All participants undergo viral load testing at Week 48.
Other: Standard of Care treatment strategy
Management of virologic failure on TLD using the Standard of Care strategy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Viral suppression at 48 weeks
Time Frame: 48 weeks post-enrollment (visit window spanning 42 to 54 weeks post-enrollment)
A plasma HIV-1 RNA viral load <50 copies/mL (FDA-snapshot definition)
48 weeks post-enrollment (visit window spanning 42 to 54 weeks post-enrollment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
Bill and Melinda Gates Foundation
University of California, San Francisco
Mbarara University of Science and Technology
University of KwaZulu

Investigators

  • Principal Investigator: Suzanne McCluskey, MD, Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 7, 2024

Primary Completion (Estimated)

June 30, 2027

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

May 6, 2022

First Submitted That Met QC Criteria

May 9, 2022

First Posted (Actual)

May 13, 2022

Study Record Updates

Last Update Posted (Actual)

March 19, 2026

Last Update Submitted That Met QC Criteria

March 17, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022P001193
  • R01AI167699 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV Infections

Clinical Trials on Individualized Care treatment strategy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Morocco

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe