Intracellular HIV-1 RNA and CD4+ T-cell activation in patients starting antiretrovirals

Ramy El-Diwany, Florian P. Breitwieser, Mary Soliman, Alyza M. Skaist, Geetha Srikrishna, Joel N. Blankson, Stuart C. Ray, Sarah J. Wheelan, David L. Thomas, Ashwin Balagopal

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To assess if the reduction in HIV-1 RNA in CD4+ T cells is correlated with the persistence of immune activation following early antiretroviral therapy (ART). Design: Clinical trial (NCT01285050). Methods: Next-generation sequencing was used to study total RNA from activated CD4+ T cells (CD38 and human leukocyte antigen - antigen D related (HLA-DR) expressing) collected from 19 treatment-naïve HIV-1/hepatitis C virus-infected patients before and early after ART initiation (≥12 weeks after plasma HIV-1 RNA <50 copies/ml). To validate comparisons, pre and post-ART measures were adjusted for input RNA and overall read number. Results: As expected, ART use was associated with a median [interquartile range (IQR)] 4.3% (2.2-8.3) reduction in the proportion of activated CD4+ T cells (P = 0.0008). Whereas in those activated CD4+ T cells no consistent differences in overall gene expression were detected, interferon-stimulated gene expression declined (P < 2 × 10-16). Pre-ART, sorted activated CD4+ T cells contained a median (IQR) of 959 (252-1614) HIV-1 reads/107 reads compared with 72 (55-152) HIV-1 reads/107 reads after at least 12 weeks of suppressive ART (P = 8 × 10-5). The decrease in HIV-1 reads in activated CD4+ T cells was associated with the change in plasma HIV-1 RNA levels (r = 0.77, P = 2 × 10-4) and the change in the proportion of activated CD4+ T cells (r = 0.70, P = 0.0016). Conclusion: Months of ART led to a marked decrease in cell-associated HIV-1 RNA and interferon-stimulated genes expression in activated CD4+ T cells that were strongly associated with the reduction in the proportion of activated CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)1405-1414
Number of pages10
JournalAIDS
Volume31
Issue number10
DOIs
StatePublished - Jun 19 2017

Keywords

  • HIV-1
  • Immune activation
  • T-cell activation
  • antiretroviral therapy
  • cell-associated HIV-1 RNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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