title: Intracellular HIV-1 RNA and CD4+ T-cell activation in patients starting antiretrovirals.
abstract: 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).
  
  
  
  Clinical trial (NCT01285050).
  
  
  
  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.
  
  
  
  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). Pre-ART, sorted activated CD4 T cells contained a median (IQR) of 959 (252-1614) HIV-1 reads/10 reads compared with 72 (55-152) HIV-1 reads/10 reads after at least 12 weeks of suppressive ART (P = 8 × 10). 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) and the change in the proportion of activated CD4 T cells (r = 0.70, P = 0.0016).
  
  
  
  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.
authors.affiliation: aDepartment of Medicine bMcKusick-Nathans Institute of Genetic Medicine,Center for Computational Biology cDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ramy
authors.initials: R
authors.lastname: El-Diwany
authors.forename: Florian P
authors.initials: FP
authors.lastname: Breitwieser
authors.forename: Mary
authors.initials: M
authors.lastname: Soliman
authors.forename: Alyza M
authors.initials: AM
authors.lastname: Skaist
authors.forename: Geetha
authors.initials: G
authors.lastname: Srikrishna
authors.forename: Joel N
authors.initials: JN
authors.lastname: Blankson
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Ray
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Wheelan
authors.forename: David L
authors.initials: DL
authors.lastname: Thomas
authors.forename: Ashwin
authors.initials: A
authors.lastname: Balagopal
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis*; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral