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

NCT ID: NCT05373758

Last Updated: 2025-03-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 648 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-07
• Study Completion Date: 2027-05-01

Brief Summary

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.

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.

Conditions

HIV Infections; AIDS; Virologic Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Standard of Care treatment strategy

Intervention Type: OTHER

Management of virologic failure on TLD using the Standard of Care strategy

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.

Group Type: EXPERIMENTAL

Individualized Care treatment strategy

Intervention Type: OTHER

Management of virologic failure on TLD using the Individualized Care strategy

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.

Group Type: EXPERIMENTAL

Immediate Switch

Intervention Type: OTHER

Management of virologic failure on TLD using the Immediate Switch strategy

Interventions

Standard of Care treatment strategy

Management of virologic failure on TLD using the Standard of Care strategy

Intervention Type: OTHER

Individualized Care treatment strategy

Management of virologic failure on TLD using the Individualized Care strategy

Intervention Type: OTHER

Immediate Switch

Management of virologic failure on TLD using the Immediate Switch strategy

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mbarara University of Science and Technology

OTHER

Sponsor Role: collaborator

University of KwaZulu

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Suzanne McCluskey

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Suzanne McCluskey, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

RK Khan Hospital Clinic

Durban, , South Africa

Site Status: RECRUITING

Mbarara City Clinic

Mbarara, , Uganda

Site Status: RECRUITING

Mbarara Regional Referral Hospital Immune Suppression Syndrome Clinic

Mbarara, , Uganda

Site Status: RECRUITING

Countries

South Africa; Uganda

Central Contacts

Suzanne McCluskey, MD

Role: CONTACT

smccluskey@mgh.harvard.edu

617-726-9488

Facility Contacts

Richard Lessells

Role: primary

Winnie Muyindike

Role: primary

Winnie Muyindike

Role: primary

Other Identifiers

R01AI167699

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2022P001193

Identifier Type: -

Identifier Source: org_study_id