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

Not Applicable

Recruiting

• Conditions: Virologic Failure; HIV Infections; AIDS
• Interventions: Other: Individualized Care treatment strategy; Other: Immediate Switch; Other: Standard of Care treatment strategy

• Registration Number: NCT05373758
• Lead Sponsor: Massachusetts General Hospital

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.

Study Timeline

• Study First Submitted: 2022-05-06
• Study First Submitted QC: 2022-05-09
• Study First Posted: 2022-05-13
• Study Start: 2024-02-07
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-03
• Last Update Posted: 2025-03-05
• Primary Completion: 2027-05-01
• Study Completion: 2027-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 648

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Individualized Care	Individualized Care treatment strategy	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.
Immediate Switch	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.
Standard of Care	Standard of Care treatment strategy	In Uganda, participants will receive management per Uganda Ministry of Health (MOH) guidelines. A reflex genotypic resistance test (GRT) is performed by MOH for individuals with a second viral load \>1,000 while on TLD. Participants will continue enhanced adherence counseling (EAC) and TLD while awaiting the GRT result. Participants will have an additional Week 24 visit for specimen collection. Participants will return for a visit after GRT results are received and a treatment decision has been made by the regional switch committee. In South Africa, participants will receive management per South Africa Department of Health guidelines. At enrollment, participants will undergo EAC and continue on TLD. At Week 24, participants will undergo repeat viral load testing. If viral load \>1,000, the participant will continue TLD and EAC. If resuppressed, participants will be maintained on TLD. All participants will undergo plasma HIV-1 RNA viral load testing at Week 48.

Primary Outcome Measures

Name	Time	Method
Viral suppression at 48 weeks	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)

Trial Locations

Locations (3)

RK Khan Hospital Clinic; 🇿🇦 Durban, South Africa

Mbarara Regional Referral Hospital Immune Suppression Syndrome Clinic; 🇺🇬 Mbarara, Uganda

Mbarara City Clinic; 🇺🇬 Mbarara, Uganda