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. 1997 Sep 15;100(6):1581–1589. doi: 10.1172/JCI119682

Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors.

O J Cohen 1, M Vaccarezza 1, G K Lam 1, B F Baird 1, K Wildt 1, P M Murphy 1, P A Zimmerman 1, T B Nutman 1, C H Fox 1, S Hoover 1, J Adelsberger 1, M Baseler 1, J Arthos 1, R T Davey Jr 1, R L Dewar 1, J Metcalf 1, D J Schwartzentruber 1, J M Orenstein 1, S Buchbinder 1, A J Saah 1, R Detels 1, J Phair 1, C Rinaldo 1, J B Margolick 1, A S Fauci 1, et al.
PMCID: PMC508340  PMID: 9294127

Abstract

HIV-1-infected long-term nonprogressors are a heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. CC chemokine receptor 5 (CCR5) has recently been identified as an important coreceptor for HIV-1 entry into CD4+ T cells. A mutant allele of CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals and partial protection against HIV disease progression in heterozygotes. The frequency of CCR5 heterozygotes is increased among HIV-1- infected long-term nonprogressors compared with progressors; however, the host defense mechanisms responsible for nonprogression in CCR5 heterozygotes are unknown. We hypothesized that nonprogressors who were heterozygous for the mutant CCR5 gene might define a subgroup of nonprogressors with higher CD4+ T cell counts and lower viral load compared with CCR5 wild-type nonprogressors. However, in a cohort of 33 HIV-1-infected long-term nonprogressors, those who were heterozygous for the mutant CCR5 gene were indistinguishable from CCR5 wild-type nonprogressors with regard to all measured immunologic and virologic parameters. Although epidemiologic data support a role for the mutant CCR5 allele in the determination of the state of long-term nonprogression in some HIV-1- infected individuals, it is not the only determinant. Furthermore, long-term nonprogressors with the wild-type CCR5 genotype are indistinguishable from heterozygotes from an immunologic and virologic standpoint.

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Selected References

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