Decreased HIV type 1 transcription in CCR5-Δ32 heterozygotes during suppressive antiretroviral therapy

J Infect Dis. 2014 Dec 1;210(11):1838-43. doi: 10.1093/infdis/jiu338. Epub 2014 Jun 16.


Individuals who are heterozygous for the CCR5-Δ32 mutation provide a natural model to examine the effects of reduced CCR5 expression on human immunodeficiency virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Δ32 heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral therapy. Cell-associated HIV RNA levels (P=.035), RNA to DNA transcriptional ratios (P=.013), and frequency of detectable HIV 2-long terminal repeat circular DNA (P=.013) were significantly lower in CD4+ T cells from CCR5-Δ32 heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5 surface expression on CD4+ T cells (r2=0.136; P=.002). Our findings suggest that curative strategies should further explore manipulation of CCR5.

Keywords: CCR5; HIV; HIV replication; HIV transcription; NF-κB; coreceptor; eradication; latency; reservoir; Δ32.

Publication types

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

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cohort Studies
  • Gene Expression Regulation, Viral*
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / genetics*
  • HIV-1 / immunology
  • Heterozygote*
  • Humans
  • Mutation*
  • Phenotype
  • RNA, Viral / genetics
  • Receptors, CCR5 / genetics*
  • Viral Load


  • RNA, Viral
  • Receptors, CCR5