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

  • Acronym: RESOLVE
  • Grant Number: 1R01AI167699-01A1
  • Effective start/end date: July 01st, 2022 June 30th, 2027
  • Funder: NATIONAL INSTITUTE OF HEALTH
  • Type: Intevation Research

Overview

Tenofovir, lamivudine, and dolutegravir (TLD) has become the predominant first-line antiretroviral therapy (ART) regimen in sub-Saharan Africa. While virologic failure on TLD is relatively rare currently, rates will inevitably increase over time, threatening epidemic control in the region. The optimal management of virologic failure on TLD is currently unknown, and policies vary widely in Sub-Saharan Africa.

Aim 1) We will conduct the RESOLVE trial, an open, parallel arm, randomized clinical trial in public sector clinics to determine the optimal strategy for management of virologic failure on first-line TLD in Sub-Saharan Africa. We will recruit 648 adolescents and adults with two viral loads >1,000 copies/mL while on first-line TLD for at least 12 months, who are in care at one of the study public-sector HIV clinics in Uganda or South Africa. We will randomize participants to one of the following strategies, stratified by clinic and prior NNRTI-exposure: a) Maintenance on TLD with switch to protease inhibitor (PI)-based second-line ART if virologic failure persists past six months; b) Individualized Care, with regimen choice based on results of genotypic resistance tests and urine tenofovir assays; or c) Immediate Switch to PI-based second-line ART.

Aim 2) We will populate the Cost-Effectiveness of Preventing AIDS Complications-International model with the clinical trial data from Aim 1 to project long-term clinical outcomes and cumulative lifetime costs. We will use simulation modeling to examine the clinical impact, costs, and cost-effectiveness of strategies to improve viral suppression after virologic failure on TLD.

Impact: We will respond to this priority research gap with data to guide global HIV policy by determining the most clinically effective and cost-effective strategy for management of virologic failure on TLD.


Participants

  • Dr. Winnie Muyindike (PI) wmuyindike@gmail.com
  • Prof. Suzanne Mc Cluskey (PI) smccluskey@mgh.harvard.edu
  • Ms. Victoria Nafuka (Project Coordinator)
  • Ms. Atuheire Anna (Finance Controller)

Publications