HIV-1 latent reservoir size and diversity are stable following brief treatment interruption

J Clin Invest. 2018 Jul 2;128(7):3102-3115. doi: 10.1172/JCI120194. Epub 2018 Jun 18.


Background: The effect of a brief analytical treatment interruption (ATI) on the HIV-1 latent reservoir of individuals who initiate antiretroviral therapy (ART) during chronic infection is unknown.

Methods: We evaluated the impact of transient viremia on the latent reservoir in participants who underwent an ATI and at least 6 months of subsequent viral suppression in a clinical trial testing the effect of passive infusion of the broadly neutralizing Ab VRC01 during ATI.

Results: Measures of total HIV-1 DNA, cell-associated RNA, and infectious units per million cells (IUPM) (measured by quantitative viral outgrowth assay [QVOA]) were not statistically different before or after ATI. Phylogenetic analyses of HIV-1 env sequences from QVOA and proviral DNA demonstrated little change in the composition of the virus populations comprising the pre- and post-ATI reservoir. Expanded clones were common in both QVOA and proviral DNA sequences. The frequency of clonal populations differed significantly between QVOA viruses, proviral DNA sequences, and the viruses that reactivated in vivo.

Conclusions: The results indicate that transient viremia from ATI does not substantially alter measures of the latent reservoir, that clonal expansion is prevalent within the latent reservoir, and that characterization of latent viruses that can reactivate in vivo remains challenging.

Trial registration: NCT02463227FUNDING. Funding was provided by the NIH.

Keywords: AIDS/HIV; Clinical Trials; T cells.

Publication types

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

MeSH terms

  • Adult
  • Anti-Retroviral Agents / administration & dosage*
  • Antibodies, Monoclonal / administration & dosage
  • Broadly Neutralizing Antibodies
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / virology
  • DNA, Viral / blood
  • DNA, Viral / genetics
  • Drug Administration Schedule
  • Genes, env
  • Genetic Variation / drug effects
  • HIV Antibodies
  • HIV Envelope Protein gp160 / genetics
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1* / classification
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • Humans
  • Male
  • Middle Aged
  • Phylogeny
  • Proviruses / classification
  • Proviruses / drug effects
  • Proviruses / genetics
  • Viral Load / drug effects
  • Viremia / drug therapy
  • Viremia / virology
  • Virus Latency / drug effects
  • Virus Latency / genetics


  • Anti-Retroviral Agents
  • Antibodies, Monoclonal
  • Broadly Neutralizing Antibodies
  • DNA, Viral
  • HIV Antibodies
  • HIV Envelope Protein gp160
  • VRC01 monoclonal antibody
  • gp160 protein, Human immunodeficiency virus 1

Associated data