HIV-1 transcriptional activity during frequent longitudinal sampling in aviremic patients on antiretroviral therapy

Steffen Leth, Rasmus Nymann, Sofie Jørgensen, Rikke Olesen, Thomas Aagaard Rasmussen, Lars Østergaard, Paul W. Denton, Martin Tolstrup, Ole Schmeltz Søgaard

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: HIV-1 transcription during suppressive antiretroviral therapy (ART) is not well understood. This is problematic as latency-reactivating agent-based HIV-1 eradication trials utilize changes in viral transcription as an efficacy biomarker. Methods: We conducted an observational cohort study enrolling aviremic, HIV-1-infected adults on long-term ART. Cell-associated unspliced (CA-US) HIV-1 RNA and total HIV-1 DNA were quantified in unfractionated CD4+ T cells monthly for a total of six consecutive visits. Random-effects models were used to determine the following: (i) proportion of variation attributable to intra-individual versus inter-individual changes; (ii) range estimate for random samples from any participant or cohort-matched individual (95% prediction interval); and (iii) range estimate for random samples from the same person (95% variation intervals expressed as fold change). Results: Among our cohort of 26 HIV-1 patients, 10.4% of variation in CA-US HIV-1 RNA was attributable to intra-individual fluctuations. Similarly, intra-individual changes also accounted for minor proportions of the variation in total HIV-1 DNA (5.1%) and RNA/DNA (28.3%). The 95% prediction interval (per 10 6 CD4+ T cells) for CA-US HIV-1 RNA and HIV-1 DNA were each approximately 2 log 10. Finally, model-derived 95% variation intervals indicate that spontaneous changes above 2.11-fold in CA-US HIV-1 RNA would occur in less than 5% of repeated measurements in an individual on long-term ART. Conclusion: The individual CA-US HIV-1 RNA levels are remarkably stable during ART. Importantly, the observed variations were less than the reported changes for latency-reactivating agent trials. These data will serve as a foundation for planning and interpreting future eradication trials.

Original languageEnglish (US)
Pages (from-to)713-721
Number of pages9
JournalAIDS
Volume30
Issue number5
DOIs
StatePublished - Mar 13 2016
Externally publishedYes

Keywords

  • antiretroviral therapy
  • HIV
  • HIV DNA
  • HIV transcription
  • latency

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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