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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • CD4-Positive T-Lymphocytes / virology
  • Chronic Disease
  • Evaluation Studies as Topic
  • HIV Infections / drug therapy
  • HIV-1 / isolation & purification*
  • HIV-1 / physiology*
  • Humans
  • Middle Aged
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Viremia / drug therapy
  • Virus Latency / drug effects*
  • Young Adult


  • Anti-HIV Agents