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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 regimens—have been explored as a strategy towards an HIV cure. RIVER is the first randomised trial to determine the effect of ART-only versus ART plus kick and kill on markers of the HIV reservoir. Methods: This phase 2, open-label, multicentre, randomised, controlled trial was undertaken at six clinical sites in the UK. Patients aged 18–60 years who were confirmed as HIV-positive within a maximum of the past 6 months and started ART within 1 month from confirmed diagnosis were randomly assigned by a computer generated randomisation list to receive ART-only (control) or ART plus the histone deacetylase inhibitor vorinostat (the kick) and replication-deficient viral vector T-cell inducing vaccines encoding conserved HIV sequences ChAdV63. HIVconsv-prime and MVA.HIVconsv-boost (the kill; ART + V + V; intervention). The primary endpoint was total HIV DNA isolated from peripheral blood CD4+ T-cells at weeks 16 and 18 after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02336074. Findings: Between June 14, 2015 and Jul 11, 2017, 60 men with HIV were randomly assigned to receive either an ART-only (n=30) or an ART + V + V (n=30) regimen; all 60 participants completed the study, with no loss-to-follow-up. Mean total HIV DNA at weeks 16 and 18 after randomisation was 3·02 log10 copies HIV DNA per 106 CD4+ T-cells in the ART-only group versus 3·06 log10 copies HIV DNA per 106 CD4+ T-cells in ART + V + V group, with no statistically significant difference between the two groups (mean difference of 0·04 log10 copies HIV DNA per 106 CD4+ T-cells [95% CI −0·03 to 0·11; p=0·26]). There were no intervention-related serious adverse events. Interpretation: This kick and kill approach conferred no significant benefit compared with ART alone on measures of the HIV reservoir. Although this does not disprove the efficacy kick and kill strategy, for future trials enhancement of both kick and kill agents will be required.

Objective To assess the occurrence of viral load greater than 50 copies/ml in patients on highly active antiretroviral therapy (HAART) having achieved less than 50 copies/ml and the chance of whether a viral load greater than 50 copies/ml would lead to a sustained and increasing viral load. Design A cohort of 553 patients on HAART with viral loads of less than 50 copies/ml were followed. Results Over a median of 56 weeks 35% of patients experienced a transient increase and 8% virological failure (two consecutive viral loads of > 400 copies/ml). Transient increases and virological failure were more common in those with greater drug experience, and those with initial raised viral load values of more than 400 copies/ml were more likely to have a sustained increase and become virological failures. Conclusion Transient increases in viral load are common, mainly in the 50-400 copies/ml range, and the majority of subsequent viral load estimations show a return to less than 50 copies/ml. A single raised viral load should lead to adherence support and intensified monitoring. Subsequent treatment decisions can then be based on evidence of true virological rebound and failure.