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J Infect Dis. 2015 Nov 1;212(9):1361-5. doi: 10.1093/infdis/jiv218. Epub 2015 Apr 15.

Precise Quantitation of the Latent HIV-1 Reservoir: Implications for Eradication Strategies.

Author information

1
Department of Medicine, University of North Carolina at Chapel Hill.
2
Department of Epidemiology, University of North Carolina at Chapel Hill.
3
Department of Medicine, University of North Carolina at Chapel Hill Department of Epidemiology, University of North Carolina at Chapel Hill Department of Microbiology and Immunology, University of North Carolina at Chapel Hill.
4
Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.

Abstract

The quantitative viral outgrowth assay (QVOA) provides a precise minimal estimate of the reservoir of resting CD4(+) T-cell infection (resting cell infection [RCI]). However, the variability of RCI over time during antiretroviral therapy (ART), relevant to assess potential effects of latency-reversing agents or other interventions, has not been fully described. We performed QVOA on resting CD4(+) T cells obtained via leukapheresis from 37 human immunodeficiency virus (HIV)-infected patients receiving stable suppressive ART for a period of 6 years. Patients who started ART during acute (n = 17) or chronic (n = 20) HIV infection were studied once HIV RNA levels were <50 copies/mL for ≥ 6 months. Using random effects analysis of 160 RCI measurements, we found that RCI declined significantly over time (P < .001), with an estimated mean half-life of 3.6 years (95% confidence interval, 2.3-8.1 years), remarkably consistent with findings of prior studies. There was no evidence of more rapid decay in acute versus chronic HIV infection (P = .99) for patients suppressed ≥ 6 months. RCI was reliably estimated with longitudinal measurements generally showing < 2-fold variation from the previous measure. When QVOA is performed in this format, RCI decreases of >6-fold were rare. We suggest that a 6-fold decline is a relevant threshold to reliably identify effects of antilatency interventions on RCI.

KEYWORDS:

HIV; IUPM; QVOA; RCI; SCA; latency

PMID:
25877550
PMCID:
PMC4601910
DOI:
10.1093/infdis/jiv218
[Indexed for MEDLINE]
Free PMC Article

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