The REVAMP study was an open-label, randomized controlled trial conducted in Uganda and South Africa which was conducted from 2016-2020. The study enrolled 840 people living with HIV on first-line antiretroviral therapy, who were failing treatment with a recent viral load >1,000 copies/milliliter (mL). Eligible participants were randomized to the WHO-based standard of care for the management of virologic failure or immediate resistance testing with the use of results to guide ART regimen decisions. The primary outcome of interest was viral suppression (<200 copies/mL) at 9 months after study enrollment and was assessed using an intention to treat analysis, where missing or absent results were considered failures. Secondary outcomes of interest were viral suppression below the limit of assay detection, viral suppression on continuation of the first line (non-nucleoside reverse transcriptase inhibitor [NNRTI]-based) therapy, drug resistance at study conclusion, and mortality, among others. We found no difference in the rate of virologic suppression nine months after enrollment between the GRT (63%, 263/417) and SOC arms (61%, 256/423, OR 1.11, 95%CI 0.83-1.49, P=0.46). Among participants with persistent failure at nine months, the prevalence of drug resistance was higher in the SOC arm (76% [78/103] versus 58% [48/82], OR 2.30, 95%CI 1.22 to 4.35, P=0.014). Other secondary outcomes, including nine-month survival and retention in care, were similar between arms. In summary, we found that the addition of genotypic resistance testing to routine care after first-line virologic failure in Uganda and South Africa did not improve rates of re-suppression. The study helps demonstrate that patients failing HIV therapy require additional support systems, and will require innovative interventions to ensure we can improve rates of re-suppression in this high-risk population. The study team is also working on an additional analysis to assess the cost-effectiveness of the intervention in the public sector and determine how drug resistance and adherence contributed to virologic failure.
