Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease.
Where this comes from
- Record sourced from PubMed, PMID 39557853.
- Also identified by DOI 10.1038/s41467-024-54116-1 and PMC identifier 11574060.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sub>1/2</sub> ~ 2.83 weeks; week 5-24: t<sub>1/2</sub> ~ 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.
Medical subject headings
- HIV Infections
- DNA, Viral
- Viral Load
- CD4-Positive T-Lymphocytes
- HIV-1
- Virus Latency