Impact of obefazimod on viral persistence, inflammation, and immune activation in people with HIV on suppressive antiretroviral therapy.

Abstract

Persistence of viral reservoirs has been observed in people with HIV (PWH), despite long-term ART, and likely contributes to chronic immune activation and inflammation. Obefazimod is a novel drug that inhibits HIV-1 replication and reduces inflammation. Here we assess whether obefazimod is safe and might impact HIV-1 persistence, chronic immune activation, and inflammation in ART-suppressed PWH. We evaluated obefazimod-related adverse events, changes in cell-associated HIV-1 DNA and RNA, residual viraemia, immunophenotype, and inflammation biomarkers in blood and rectal tissue. We compared 24 ART-suppressed PWH who received daily doses of 50 mg of obefazimod for 12wks (n = 13), or 150 mg for 4wks (n = 11) and 12 HIV-negative individuals who received 50 mg for 4wks. 50 or 150 mg doses of obefazimod were safe, although 150 mg dose showed inferior tolerability. 150 mg dose reduced HIV-1 DNA (p = 0.008, median fold-change = 0.6), and residual viraemia in all individuals with detectable viraemia at baseline. Furthermore, obefazimod upregulated miR-124 in all participants, reduced the activation markers CD38, HLA-DR, and PD-1, and several inflammation biomarkers. The effect of obefazimod by reducing chronic immune activation and inflammation suggests a potential role for the drug in virus remission strategies involving other compounds that can activate immune cells, such as latency-reversing agents.