Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease

Alton Barbehenn (), Lei Shi, Junzhe Shao, Rebecca Hoh, Heather M. Hartig, Vivian Pae, Sannidhi Sarvadhavabhatla, Sophia Donaire, Caroline Sheikhzadeh, Jeffrey Milush, Gregory M. Laird, Mignot Mathias, Kristen Ritter, Michael J. Peluso, Jeffrey Martin, Frederick Hecht, Christopher Pilcher, Stephanie E. Cohen, Susan Buchbinder, Diane Havlir, Monica Gandhi, Timothy J. Henrich, Hiroyu Hatano, Jingshen Wang, Steven G. Deeks and Sulggi A. Lee ()
Additional contact information
Alton Barbehenn: University of California San Francisco
Lei Shi: University of California Berkeley
Junzhe Shao: University of California Berkeley
Rebecca Hoh: University of California San Francisco
Heather M. Hartig: University of California San Francisco
Vivian Pae: University of California San Francisco
Sannidhi Sarvadhavabhatla: University of California San Francisco
Sophia Donaire: University of California San Francisco
Caroline Sheikhzadeh: University of California San Francisco
Jeffrey Milush: University of California San Francisco
Gregory M. Laird: AccelevirDiagnostics
Mignot Mathias: AccelevirDiagnostics
Kristen Ritter: AccelevirDiagnostics
Michael J. Peluso: University of California San Francisco
Jeffrey Martin: University of California San Francisco
Frederick Hecht: University of California San Francisco
Christopher Pilcher: University of California San Francisco
Stephanie E. Cohen: University of California San Francisco
Susan Buchbinder: San Francisco Department of Public Health
Diane Havlir: University of California San Francisco
Monica Gandhi: University of California San Francisco
Timothy J. Henrich: University of California San Francisco
Hiroyu Hatano: University of California San Francisco
Jingshen Wang: University of California Berkeley
Steven G. Deeks: University of California San Francisco
Sulggi A. Lee: University of California San Francisco

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Despite antiretroviral therapy (ART), HIV persists in latently-infected cells (the HIV reservoir) which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people living with HIV (PLWH) treated during acute infection, we developed a mathematical model to predict reservoir decay from peripheral CD4 + T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t1/2 ~ 2.83 weeks; week 5-24: t1/2 ~ 15.4 weeks) that extended out to 1 year. These estimates were ~5-fold faster than prior decay estimates among chronic treated PLWH. Defective DNA had a similar biphasic pattern, but data were more variable. Predicted intact and defective decay rates were faster for PLWH with earlier timing of ART initiation, higher initial CD4 + T cell count, and lower pre-ART viral load. In this study, we advanced our limited understanding of HIV reservoir decay at the time of ART initiation, informing future curative strategies targeting this critical time.

Date: 2024
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DOI: 10.1038/s41467-024-54116-1

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