Causal pathways for CCR5 genotype and HIV progression

Jeremy M.G. Taylor, Yan Wang, Linda Ahdieh, Joan S. Chmiel, Roger Detels, Janis V. Giorgi, Richard Kaslow, Lawrence Kingsley, Joseph Margolick

Research output: Contribution to journalArticlepeer-review

Abstract

A homozygous 32-bp deletion in the gene encoding CCR5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1, and heterozygosity for the deletion is associated with delayed disease progression in persons infected with HIV-1. We investigated the effect of CCR5 heterozygosity on disease progression as measured by both CD4+ T-cell count decline and the occurrence of clinical AIDS symptoms. Using a unified statistical model for CD4 count progression and AIDS development, we examined whether the effect of CCR5 heterozygosity on clinical AIDS is direct or indirect through its effect on CD4 counts. Based on data from the Multicenter AIDS Cohort Study, we noted a protective effect of CCR5 heterozygosity on both CD4 cell count progression and on AIDS occurrence. Furthermore, we found that this protective effect on the occurrence of AIDS was completely mediated through an effect on the CD4 marker. Additional adjustment for the effect of an initial viral load measurement indicate that CCR5 heterozygosity did not have predictive value for either CD4 progression or the development of AIDS beyond its association with early viral load.

Original languageEnglish (US)
Pages (from-to)160-171
Number of pages12
JournalJournal of acquired immune deficiency syndromes
Volume23
Issue number2
DOIs
StatePublished - Feb 1 2000

Keywords

  • AIDS
  • CCR5 heterozygosity
  • CD4 T cells
  • HIV
  • Longitudinal modeling
  • Proportional hazards model
  • Viral load

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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