Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease
Alton Barbehenn, Lei Shi, Junzhe Shao, Rebecca Hoh, Heather Hartig, Vivian Pae, Sannidhi Sarvadhavabhatla, Sophia Donaire, Caroline Sheikhzadeh, Jeffrey M. Milush, Gregory M. Laird, M. Mathias, Kristen D. Ritter, Michael J. Peluso, Jeffrey N. Martin, Frederick Hecht, Christopher D. Pilcher, Stephanie E. Cohen, Susan Buchbinder, Diane V. Havlir, Monica Gandhi, Timothy J. Henrich, Hiroyu Hatano, Jingshen Wang, Steven G. Deeks, Sulggi A. Lee
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: t 1/2 ~ 2.83 weeks; week 5-24: t 1/2 ~ 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.