Effects of CCR5-δ32 and CCR2-64I alleles on HIV-1 disease progression: The protection varies with duration of infection

Stephanie A. Mulherin, Thomas R. O'Brien, John P.A. Ioannidis, James J. Goedert, Susan P. Buchbinder, Roel A. Coutinho, Beth D. Jamieson, Laurence Meyer, Nelson L. Michael, Giuseppe Pantaleo, G. Paolo Rizzardi, Hanneke Schuitemaker, Haynes W. Sheppard, Ioannis D. Theodorou, David Vlahov, Philip S. Rosenberg

    Research output: Contribution to journalArticle

    Abstract

    Objective: To examine temporal variation in the effects of CCR5-Δ32 and CCR2-64I chemokine receptor gene polymorphisms on HIV-1 disease progression. Design: Pooled analysis of individual patient data from 10 cohorts of HIV-1 seroconverters from the United States, Europe, and Australia. Methods: We studied HIV-1 seroconverters of European (n = 1635) or African (n = 215) ancestry who had been genotyped for CCR5-Δ32 and CCR2-64I. We used Cox proportional hazards models with time-varying coefficients to determine whether the genetic protection against AIDS (1987 case definition) and death varied with time since seroconversion. Results: Protection against AIDS conferred by CCR5-Δ32 held constant at a 31% (RH 0.69, 95% CI 0.54, 0.88) reduction in risk over the course of HIV-1 infection, whereas protection against death held constant at a 39% reduction in risk (RH 0.61, 95% CI 0.45, 0.88). When the period from AIDS to death was isolated, the survival benefit of CCR5-Δ32 diminished 2 years after AIDS. Protection against AIDS conferred by CCR2-64I was greatest early in the disease course. Compared with individuals without CCR5-Δ32 or CCR2-64I, individuals with one or two copies of CCR2-64I had a 58% lower risk of AIDS during the first 4 years after seroconversion (RH 0.42, 95% CI 0.23, 0.76), a 19% lower risk during the subsequent 4 years (RH 0.81, 95% CI 0.59, 1.12), and no significant protection thereafter. Conclusion: The protection against AIDS provided by CCR5-Δ32 is continuous during the course of infection. In contrast, the protection provided by CCR2-64I is greatest early in the course of infection.

    Original languageEnglish (US)
    Pages (from-to)377-387
    Number of pages11
    JournalAIDS
    Volume17
    Issue number3
    DOIs
    StatePublished - Feb 14 2003

    Keywords

    • AIDS
    • Alleles
    • CCR2
    • CCR5
    • Chemokine receptors
    • HIV-1

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Infectious Diseases

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  • Cite this

    Mulherin, S. A., O'Brien, T. R., Ioannidis, J. P. A., Goedert, J. J., Buchbinder, S. P., Coutinho, R. A., Jamieson, B. D., Meyer, L., Michael, N. L., Pantaleo, G., Rizzardi, G. P., Schuitemaker, H., Sheppard, H. W., Theodorou, I. D., Vlahov, D., & Rosenberg, P. S. (2003). Effects of CCR5-δ32 and CCR2-64I alleles on HIV-1 disease progression: The protection varies with duration of infection. AIDS, 17(3), 377-387. https://doi.org/10.1097/00002030-200302140-00012