Final results of the RIVER trial have been published in Lancet HIV.
RIVER, conducted in London and Brighton and funded by the Medical Research Council (MRC), was the first ever randomised controlled trial of an HIV cure strategy. The aim was to eliminate the reservoir of HIV-infected cells which remains even in ART-treated patients with undetectable viral load.
Eagerly awaited headline results released in 2018 were negative, to the disappointment of the HIV community. The final paper confirms this result.
RIVER tested the 'kick and kill' approach. In addition to ART, participants randomised to the experimental arm received the histone deacetylase inhibitor vorinostat (the ‘kick’, designed to ‘wake up’ the HIV reservoir) together with two replication-deficient viral vector T-cell inducing vaccines encoding conserved HIV sequences. It was hoped these would stimulate the immune system and train it to destroy HIV (the 'kill'). The primary endpoint was total HIV DNA isolated from peripheral blood CD4 + T-cells at weeks 16 and 18.
The Lancet HIV paper confirms that the treatment conferred no significant benefit compared with ART alone on measures of the HIV reservoir. This does not disprove the efficacy kick and kill strategy, the authors note: all the separate parts of the kick and kill approach worked as expected and were safe. However, for future trials both the kick and kill agents will need to be enhanced.
Lancet HIV called the study a disappointing negative with many lessons for HIV cure research. It is important that future HIV cure trials should follow RIVER’s example and use a randomised controlled design that compares outcomes to an ART-only group, said Professor Abdel Babiker of the MRC Clinical Trials Unit at University College London.
