Autologous neutralizing antibody responses after antiretroviral therapy in acute and early HIV-1

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Abstract

BACKGROUND Early antiretroviral therapy initiation (ARTi) in HIV-1 restricts reservoir size and diversity while preserving immune function, potentially improving opportunities for immunotherapeutic cure strategies. For antibody-based cure approaches, the development of autologous neutralizing antibodies (anAbs) after acute/early ARTi is relevant but is poorly understood.METHODS We characterized antibody responses in a cohort of 23 participants following ARTi in acute HIV (<60 days after acquisition) and early HIV (60–128 days after acquisition).RESULTS Plasma virus sequences at the time of ARTi revealed evidence of escape from anAbs after early, but not acute, ARTi. HIV-1 envelopes representing the transmitted/founder virus(es) (acute ARTi) or escape variants (early ARTi) were tested for sensitivity to longitudinal plasma IgG. After acute ARTi, no anAb responses developed over months to years of suppressive ART. In 2 of the 3 acute ARTi participants who experienced viremia after ARTi, however, anAbs arose shortly thereafter. After early ARTi, anAbs targeting those early variants developed between 12 and 42 weeks of ART and continued to increase in breadth and potency thereafter.CONCLUSION Results indicate a threshold of virus replication (~60 days) required to induce anAbs, after which they continue to expand on suppressive ART to better target the range of reservoir variants.TRIAL REGISTRATION ClinicalTrials.gov NCT02656511.FUNDING NIH grants U01AI169767, R01AI162646, UM1AI164570, UM1AI164560, U19AI096109, K23GM112526, T32AI118684, P30AI045008, P30AI027763, R24AI067039; Gilead Sciences grant INUS2361354; Viiv Healthcare grant A126326.

Authors

Gregory D. Whitehill, Jaimy Joy, Francesco E. Marino, Ryan Krause, Suvadip Mallick, Hunter Courtney, Kyewon Park, John Carey, Rebecca Hoh, Heather Hartig, Vivian Pae, Sannidhi Sarvadhavabhatla, Sophia Donaire, Steven G. Deeks, Rebecca M. Lynch, Sulggi A. Lee, Katharine J. Bar