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15 November 1997 | Volume 127 Issue 10 | Pages 882-890
Background: Heterozygosity for a 32-nucleotide deletion in the C-C chemokine receptor 5 gene (CCR5 delta32) is associated with delayed disease progression in persons infected with HIV-1.
Objective: To compare the predictive value of CCR5 genotype with that of established markers in the clinical course of HIV-1 infection.
Design: Retrospective longitudinal study and nested case–control study. The latter included only long-term survivors, who were individually matched with progressors.
Setting: Amsterdam, the Netherlands.
Participants: 364 homosexual men with HIV-1 infection.
Measurements: Polymerase chain reaction was used for CCR5 genotyping. Univariate and multivariate Cox proportional-hazard analyses were done for disease progression with CCR5 genotype, CD4+ T-lymphocyte counts, T-lymphocyte function, HIV-1 biological phenotype (syncytium-inducing or non-syncytium-inducing HIV-1), and viral RNA load in serum as covariates.
Results: In the case–control study, 48% of long-term survivors were heterozygous for CCR5 delta32 compared with 9% of progressors (odds ratio, 6.9 [95% CI, 1.9 to 24.8]). In the total study sample, CCR5 delta32 heterozygotes had significantly delayed disease progression (P < 0.001; relative hazard, 0.4 [CI, 0.3 to 0.6]), a 1.5-fold slower decrease in CD4+ T-lymphocyte count (P = 0.01), and a 2.6-fold lower viral RNA load (P = 0.01) at approximately 2.3 years after seroconversion compared with CCR5 wild-type homozygotes. At the end of the study, both groups showed the same prevalence of syncytium-inducing HIV-1, but CCR5 delta32 heterozygotes had a delayed conversion rate. The protective effect of CCR5 delta32 heterozygosity was stronger in the presence of only non-syncytium-inducing HIV-1. The CCR5 genotype predicted disease progression independent of viral RNA load, CD4 T-lymphocyte counts, T-lymphocyte function, and HIV-1 biological phenotype.
Conclusions: The addition of CCR5 genotype to currently available laboratory markers may allow better estimation of the clinical course of HIV-1 infection.
Author and Article Information
From the Central Laboratory of the Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam Academic Medical Center, and Municipal Health Service Amsterdam, Amsterdam, the Netherlands.
ARTICLE
Association between CCR5 Genotype and the Clinical Course of HIV-1 Infection
Acknowledgments: The authors thank L. Berger, A. Holwerda, E. Hovenkamp, J. van de Hulst, and E. Poelstra for technical assistance and M.R. Klein and A.B. van 't Wout for critical reading of the manuscript.
Grant Support: By the Netherlands Foundation for Preventive Medicine grant 28-2547 within the Stimulation Program AIDS Research of the Dutch Programme Committee for AIDS Research (Programma Coordinatie Commissie AIDS Onderzoele, grant 95-026).
Requests for Reprints: Hanncke Schuitemaker, PhD, Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands.
Current Author Addresses: Drs. de Roda Husman, Koot, Miedema, and Schuitemaker. Ms. Brouwer, Ms. Broersen, and Ms. Roos: Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, Department of Clinical Viro-Immunology, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands.
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