Enhanced HIV-1 Control After Antibody Therapy is Associated with Autologous Antibodies and Reservoir Clearance in the RIO trial

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Abstract RIO is an ongoing double blind randomized placebo controlled human trial in which participants that started antiretroviral therapy (ART) during primary or early-stage infection underwent treatment interruption and were randomly assigned to a group receiving one or two doses of two long acting broadly neutralizing antibodies 3BNC117-LS and 10-1074-LS (Arm A, n = 34), or saline (Arm B, n = 34). The primary clinical study met its primary endpoint and was published elsewhere, demonstrating significantly delayed viral rebound and prolonged ART-free control in participants receiving bNAbs compared to placebo. The infusions were generally safe and well tolerated. Here we report on pre-specified secondary analyses examining viral rebound, antibody sensitivity, and reservoir dynamics, as well as exploratory analyses of rebound virus evolution and autologous antibody activity. Pre-infusion reservoir measurements showed low levels of intact proviral HIV-1 DNA in circulating CD4+ T cells in both arms. The rebounding viruses in participants that received the antibodies, showed significant selection for resistance to 10-1074-LS but not to 3BNC117-LS. Notably, there was a significant correlation between greater initial reservoir sensitivity to autologous antibodies and to 10-1074 and time to rebound. Finally, comparison of pre-infusion and pre-rebound HIV-1 proviral reservoir showed a decrease in intact but not defective proviruses in Arm A but not in Arm B. Together, these findings suggest that baseline humoral immunity and prolonged exposure to LS-bNAbs may shape post-treatment viral rebound dynamics in individuals that initiate ART during primary infection. ClinicalTrials.gov identifier: NCT04319367

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