Nature Communications (Nov 2024)
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,
- Sulggi A. Lee
Affiliations
- Alton Barbehenn
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Lei Shi
- Department of Biostatistics, University of California Berkeley
- Junzhe Shao
- Department of Biostatistics, University of California Berkeley
- Rebecca Hoh
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Heather M. Hartig
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Vivian Pae
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Sannidhi Sarvadhavabhatla
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Sophia Donaire
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Caroline Sheikhzadeh
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Jeffrey Milush
- Department of Medicine, Division of Experimental Medicine, University of California San Francisco
- Gregory M. Laird
- AccelevirDiagnostics
- Mignot Mathias
- AccelevirDiagnostics
- Kristen Ritter
- AccelevirDiagnostics
- Michael J. Peluso
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Jeffrey Martin
- Department of Biostatistics & Epidemiology, University of California San Francisco
- Frederick Hecht
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Christopher Pilcher
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Stephanie E. Cohen
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Susan Buchbinder
- San Francisco Department of Public Health
- Diane Havlir
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Monica Gandhi
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Timothy J. Henrich
- Department of Medicine, Division of Experimental Medicine, University of California San Francisco
- Hiroyu Hatano
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Jingshen Wang
- Department of Biostatistics, University of California Berkeley
- Steven G. Deeks
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- Sulggi A. Lee
- Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco
- DOI
- https://doi.org/10.1038/s41467-024-54116-1
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
