Limited protective effect of the CCR5Delta32/CCR5Delta32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

J Infect Dis. 2003 Jan 15;187(2):215-25. doi: 10.1086/345881. Epub 2003 Jan 6.

Abstract

The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2% of the Scandinavian population) and a rapid disease course. His HIV V3 region contained genotypic features attributable to X4 virus and resembled functionally verified X4 virus and virus from patients treated with a CD4 cell-stimulating drug, tucaresol. Age-related differences in disease progression rate and survival time were seen for CCR5/CCR5 patients. Surprisingly, no protective effect of the CCR5/CCR5Delta32 genotype on disease progression or survival was seen for children but was evident for adults. Age group-related immunologic differences might explain this variation, and transmission route and/or viral phenotype variation within donor virus may be related to the limited protection of the CCR5Delta32/CCR5Delta32 genotype. Sequence comparisons indicate that X4 virus can be selected in vivo due to either absence of CCR5 receptors or relative increase of CXCR4 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aging / genetics
  • Aging / physiology
  • Amino Acid Sequence
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Cytomegalovirus Infections / complications
  • Cytomegalovirus Infections / genetics
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • HIV / classification*
  • HIV / isolation & purification
  • HIV / physiology
  • HIV Infections / complications*
  • HIV Infections / epidemiology
  • HIV Infections / genetics*
  • HIV Infections / virology
  • Hemophilia A / complications*
  • Hemophilia A / genetics
  • Hemophilia B / complications*
  • Hemophilia B / genetics
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Receptors, CCR5 / chemistry
  • Receptors, CCR5 / genetics*
  • Risk Factors
  • Survival Rate

Substances

  • Receptors, CCR5