Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study.

objectivesTo assess the safety and tolerability as well as antiretroviral impact of ABX464, an oral investigational drug with a novel mechanism of HIV-1 inhibition (ClinicalTrials.gov NCT02735863).

methodsRandomised, double-blind, placebo-controlled, Phase IIa study in individuals living with HIV-1 on antiretroviral therapy at six clinical centres in Spain, France and Belgium. ABX464 was administered once a day to 22 fully controlled HIV-1-positive participants at two doses (50 mg,

resultsTwenty-six of the 30 randomly allocated participants completed the study according to the study protocol. ABX464 was found to be safe and well tolerated with the majority of adverse events (AEs) being mild or moderate. Of the participants, 22 (73.3%) experienced treatment-associated AEs (93.8%, 66.7%, 37.5% in the ABX464 150-mg, 50-mg dose and placebo arms, respectively). Percentages for combined grade 3/4 AEs for the three arms were 6.3%, 0% and 12.5%, respectively. Median time (Kaplan-Meier estimates) to viral rebound for ABX464 150-mg, 50-mg and placebo arms were 12.0 (95% confidence interval [CI]: 10-15), 15.5 (95% CI 14-22) and 15.5 (95% CI 1-22) days, respectively with no significant difference between the 150-mg treatment arm and placebo. Median changes in total HIV-1 DNA copies/10

conclusionsThis small controlled study confirmed the good safety and tolerability of ABX464 and provides some evidence of a potential reduction of the HIV-1 reservoir in terms of HIV-1 DNA levels in PBMCs when it was added to an HIV-1 protease inhibitor-based regimen. These results will need to be confirmed in a larger study.