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

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.