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