Journal Article

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

Donaire, Sophia, Milush, Jeffrey, Peluso, Michael J., Laird, Gregory M., Pilcher, Christopher, Cohen, Stephanie E., Hatano, Hiroyu, Wang, Jingshen, Shi, Lei, Pae, Vivian, Henrich, Timothy J., Barbehenn, Alton, Martin, Jeffrey, Havlir, Diane, Deeks, Steven G., Mathias, Mignot, Sarvadhavabhatla, Sannidhi, Gandhi, Monica, Shao, Junzhe, Hartig, Heather M., Sheikhzadeh, Caroline, Buchbinder, Susan, Ritter, Kristen, Lee, Sulggi A., Hoh, Rebecca, Hecht, Frederick

2024

Overview

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. HIV reservoir decay is less well studied in acute infection. Here, the authors show that reservoir decay rates are biphasic and 5x faster in people initiating antiretroviral therapy during acute HIV than prior estimates for chronic HIV. Higher initial CD4+ counts and lower viral loads predicted faster decay.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/23 / 38/77 / 49/22 / 631/114/2397 / 631/326/596/1787 / 631/326/596/2564 / 692/308/575 / Acute Disease / Adult / Anti-HIV Agents - therapeutic use / Antiretroviral agents / Antiretroviral drugs / Antiretroviral therapy / CD4 antigen / CD4 Lymphocyte Count / CD4-Positive T-Lymphocytes - virology / Cell culture / Chronic infection / Decay / Decay rate / Deoxyribonucleic acid / DNA / DNA, Viral / Drug therapy / Estimates / Female / HIV / HIV Infections - drug therapy / HIV Infections - virology / HIV-1 - genetics / HIV-1 - physiology / Human immunodeficiency virus / Humanities and Social Sciences / Humans / Longitudinal Studies / Lymphocytes / Lymphocytes T / Male / Mathematical models / Middle Aged / Models, Theoretical / multidisciplinary / Science / Science (multidisciplinary) / Viral Load / Virus Latency