A randomized comparison of antiretroviral therapy alone versus antiretroviral therapy with a 'kick-and-kill' approach, on measures of the HIV reservoir amongst participants with recent HIV infection: the RIVER trial

Summary Background: Antiretroviral therapy (ART) cannot cure HIV infection because of a persistent reservoir of latently infected cells. Approaches that force HIV transcription from these cells, making them susceptible to killing - termed ���kick and kill��� - have been explored as a strategy towards an HIV cure. RIVER is the first randomized trial to determine the impact of ART alone versus ART plus ���kick-and-kill��� on markers of the HIV reservoir. Methods: RIVER (Trial registration: NCT02336074) was an open-label, multicenter, 1:1 randomized controlled trial of ART-only (control) versus ART plus the histone deacetylase inhibitor vorinostat (the ���kick���) and replication-deficient viral vector vaccines encoding conserved HIV sequences ChAdV63.HIVconsv-prime, MVA.HIVconsv-boost T-cell vaccination (the ���kill���) (ART+V+V; intervention) in HIV-positive adults treated in recent HIV-infection. The primary endpoint was total HIV DNA in peripheral blood CD4+ T-cells at weeks 16 and 18 post-randomization. Secondary endpoints included safety, alternative measures of the HIV reservoir including quantitative viral outgrowth, HIV-specific T-cell frequencies, and CD8+ T-cell mediated viral inhibition. Findings: Between December 2015 and November 2017, 60 HIV-positive male participants were randomized (computer-based and stratified by time since diagnosis; 30 participants in each trial arm) and completed the study interventions, with no loss-to-follow-up. There were no intervention-related serious adverse events. Mean total HIV DNA at weeks 16 and 18 was 3.02 log10 copies HIV DNA/106 CD4+ T-cells in the control and 3.06 log10 copies HIV DNA/106 CD4+ T-cells in the intervention arm, with no statistically significant difference (mean difference of 0.04 (95%CI -0.03, 0.11) log10 total HIV DNA copies/106 CD4+ T-cells (p=0.26)). Interpretation: This ���kick-and-kill��� approach conferred no significant benefit compared to ART alone on measures of the HIV reservoir. Although this does not disprove the ���kick and kill��� strategy, for future trials significant enhancement of both ���kick��� and ���kill��� agents will be required.
Medical Research Council (MR/L00528X/1).