Effect of short-term antiretroviral therapy interruption on levels of integrated HIV DNA

Zachary Strongin, Radwa Sharaf, D. Jake VanBelzen, Jeffrey M. Jacobson, Elizabeth Connick, Paul Volberding, Daniel J. Skiest, Rajesh T. Gandhi, Daniel R. Kuritzkes, Una O'Doherty, Jonathan Z. Li

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Analytic treatment interruption (ATI) studies are required to evaluate strategies aimed at achieving ART-free HIV remission, but the impact of ATI on the viral reservoir remains unclear. We validated a DNA size selection-based assay for measuring levels of integrated HIV DNA and applied it to assess the effects of short-term ATI on the HIV reservoir. Samples from participants from four AIDS Clinical Trials Group ATI studies were assayed for integrated HIV DNA levels. Cryopreserved peripheral blood mononuclear cells (PBMCs) were obtained for 12 participants with available samples pre-ATI and approximately 6 months after ART resumption. Four participants also had samples available during the ATI. The median duration of ATI was 12 weeks. Validation of the HIV integrated DNA size-exclusion (HIDE) assay was performed using samples spiked with unintegrated HIV DNA, HIV-infected cell lines, and participant PBMCs. The HIDE assay eliminated 99% of unintegrated HIV DNA species and strongly correlated with the established Alu-gag assay. For the majority of individuals, integrated DNA levels increased during ATI and subsequently declined upon ART resumption. There was no significant difference in the levels of integrated HIV DNA between the pre- and post-ATI time points, with a median ratio of post- to pre-ATI HIV DNA levels of 0.95. Using a new integrated HIV DNA assay, we found minimal change in the levels of integrated HIV DNA in participants who underwent an ATI, followed by 6 months of ART. This suggests that short-term ATI can be conducted without a significant impact on the levels of integrated proviral DNA in the peripheral blood.

Original languageEnglish (US)
Article numbere00285-18
JournalJournal of virology
Volume92
Issue number12
DOIs
StatePublished - Jun 1 2018

Keywords

  • Assay
  • HIV
  • Integrated DNA
  • Reservoir
  • Treatment interruption

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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