title: Precise Quantitation of the Latent HIV-1 Reservoir: Implications for Eradication Strategies.
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.
authors: Department of Medicine, University of North Carolina at Chapel Hill.
authors: Amanda M
authors: AM
authors: Crooks
authors: Department of Medicine, University of North Carolina at Chapel Hill.
authors: Rosalie
authors: R
authors: Bateson
authors: Department of Epidemiology, University of North Carolina at Chapel Hill.
authors: Anna B
authors: AB
authors: Cope
authors: Department of Medicine, University of North Carolina at Chapel Hill.
authors: Noelle P
authors: NP
authors: Dahl
authors: Department of Medicine, University of North Carolina at Chapel Hill.
authors: Morgan K
authors: MK
authors: Griggs
authors: Department of Medicine, University of North Carolina at Chapel Hill.
authors: JoAnn D
authors: JD
authors: Kuruc
authors: Department of Medicine, University of North Carolina at Chapel Hill.
authors: Cynthia L
authors: CL
authors: Gay
authors: Department of Medicine, University of North Carolina at Chapel Hill.
authors: Joseph J
authors: JJ
authors: Eron
authors: 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.
authors: David M
authors: DM
authors: Margolis
authors: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
authors: Ronald J
authors: RJ
authors: Bosch
authors: Department of Medicine, University of North Carolina at Chapel Hill.
authors: Nancie M
authors: NM
authors: Archin
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002908:Chronic Disease; D005069:Evaluation Studies as Topic; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000302:isolation & purification* / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014766:Viremia / Q000188:drug therapy; D017735:Virus Latency / Q000187:drug effects*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents
keywords: HIV; IUPM; QVOA; RCI; SCA; latency