Autologous neutralizing antibody responses after antiretroviral therapy in acute and early HIV-1
Authors
Gregory D. Whitehill, Department of Medicine, Division of Infectious Disease, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America.
Jaimy Joy, Department of Medicine, Division of Infectious Disease, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America.
Francesco E. Marino, Department of Medicine, Division of Infectious Disease, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America.
Ryan J. Krause, Department of Medicine, Division of Infectious Disease, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America.
Suvadip Mallick, Department of Medicine, Division of Infectious Disease, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America.
Hunter M. Courtney, Department of Medicine, Division of Infectious Disease, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America.
Kyewon Park, Center for AIDS Research, Virus and Reservoirs Technology Core, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America.
John W. Carey, Center for AIDS Research, Virus and Reservoirs Technology Core, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America.
Rebecca Hoh, Department of Medicine, Division of HIV, Infectious Diseases and Global Med, UCSF, San Francisco, United States of America.
Heather Hartig, Department of Medicine, Division of HIV, Infectious Diseases and Global Med, UCSF, San Francisco, United States of America.
Vivian Pae, Department of Medicine, Division of HIV, Infectious Diseases and Global Med, UCSF, San Francisco, United States of America.
Sannidhi Sarvadhavabhatla, Department of Medicine, Division of HIV, Infectious Diseases and Global Med, UCSF, San Francisco, United States of America.
Maria Sophia Donaire, Department of Medicine, Division of HIV, Infectious Diseases and Global Med, UCSF, San Francisco, United States of America.
Steven G. Deeks, Department of Medicine, Division of HIV, Infectious Diseases and Global Med, UCSF, San Francisco, United States of America.
Rebecca M. Lynch, Department of Microbiology, Immunology and Tropical Medicine, School of Med, George Washington University, Washington, United States of America.
Sulggi A. Lee, Department of Medicine, Division of HIV, Infectious Diseases and Global Med, UCSF, San Francisco, United States of America.
Katharine J. Bar, Department of Medicine, Division of Infectious Disease, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America.
Document Type
Journal Article
Publication Date
4-23-2024
Journal
The Journal of clinical investigation
Keywords
AIDS vaccine; AIDS/HIV; Adaptive immunity
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 (anAb) after acute/early ARTi is relevant, but poorly understood. METHODS: We characterize antibody responses in a cohort of 23 participants following ARTi in acute HIV (<60 days after infection) and early HIV (60-128 days after infection). RESULTS: Plasma virus sequences at the time of ARTi revealed evidence of escape from anAbs after early, but not acute, ARTi. HIV-1 Envs 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 two of the three 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. CONCLUSIONS: 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: NCT02656511FUNDING. National Institutes of Health grants U01AI169767; R01AI162646; UM1AI164570; UM1AI164560; U19AI096109; K23GM112526; T32AI118684, P30-AI-045008, P30 AI027763, R24 AI067039. Gilead Sciences grant INUS2361354; Viiv healthcare grant A126326.
APA Citation
Whitehill, Gregory D.; Joy, Jaimy; Marino, Francesco E.; Krause, Ryan J.; Mallick, Suvadip; Courtney, Hunter M.; Park, Kyewon; Carey, John W.; Hoh, Rebecca; Hartig, Heather; Pae, Vivian; Sarvadhavabhatla, Sannidhi; Donaire, Maria Sophia; Deeks, Steven G.; Lynch, Rebecca M.; Lee, Sulggi A.; and Bar, Katharine J., "Autologous neutralizing antibody responses after antiretroviral therapy in acute and early HIV-1" (2024). GW Authored Works. Paper 4685.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4685
Department
Microbiology, Immunology, and Tropical Medicine
