Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease
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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 cri..., Individuals with newly diagnosed acute (<100 days) from HIV infection were enrolled in the UCSF Treat Acute HIV cohort and co-enrolled in the UCSF SCOPE HIV cohort, an ongoing longitudinal study of over 2,500 PWH. Eligible participants were provided same-day ART initiation with tenofovir/emtricitabine (TDF/FTC, then TAF/FTC once available in 2016) + dolutegravir (DTG) and linked to clinical care. Individuals reporting concomitant PrEP use (<100 days from any potential exposure to HIV by history and/or clinical test results) were also started on darunavir+ritonavir (DRV/r) as a fourth drug, which was continued until confirmation of baseline HIV genotyping test results (Monogram Biosciences, South San Francisco, CA, U.S.A.). Additional ART changes necessary for clinical care (e.g., laboratory abnormalities, drug-drug interactions, and/or participant preference) were honored and adjusted during the period of study. Participants signed a release of information which allowed clinical d..., , # Rapid Biphasic Decay of Intact and Defective HIV DNA Reservoir During Acute Treated HIV Disease
[https://doi.org/10.5061/dryad.q573n5tsd](https://doi.org/10.5061/dryad.q573n5tsd)
## Description of the data and file structure
Data were collected from individuals with newly diagnosed acute (<100 days) from HIV infection were enrolled in the UCSF Treat Acute HIV cohort. Eligible participants were started on antiretroviral therapy (ART) and enrolled in our study. A total of 67 participants were enrolled. Study visits were scheduled at initial visit (week 0), results visit (week 2), and weeks 4, 8, 12, 16, 20, and 24. Baseline clinical measurements (CD4+ T cell count, HIV plasma viral load, estimated date of infection, and demographics) were taken at the initial visit. HIV plasma viral load (quantified with Abbott Real Time PCR assay, limit of detection <40 copies/mL) and HIV DNA reservoir size (quantified with IPDA) were taken at each study visit.Â
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创建时间:
2024-11-20



