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Effects of CCR5-Delta 32 and CCR2-64I alleles on disease progression of perinatally HIV-1-infected children: an international meta-analysis

  1. Author:
    Ioannidis, J. P. A.
    Contopoulos-Ioannidis, D. G.
    Rosenberg, P. S.
    Goedert, J. J.
    De Rossi, A.
    Espanol, T.
    Frenkel, L.
    Mayaux, M. J.
    Newell, M. L.
    Pahwa, S. G.
    Rousseau, C.
    Scarlatti, G.
    Sei, S.
    Sen, L.
    O'Brien, T. R.

  2. Author Address

    Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece Univ Ioannina, Dept Pediat, Sch Med, GR-45110 Ioannina, Greece Fdn Res & Technol Hellas, Inst Biomed Res, Ioannina, Greece Tufts Univ, New England Med Ctr, Dept Med, Boston, MA 02111 USA George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20052 USA NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA Univ Padua, AIDS Reference Ctr, Oncol Sect, Dept Oncol & Surg Sci, I-35100 Padua, Italy Hosp Gen Valle Hebron, Immunol Unit, Barcelona, Spain Univ Washington, Sch Med, Childrens Hosp & Reg Med Ctr, Div Pediat Infect Dis,Dept Pediat, Seattle, WA 98195 USA INSERM, Paris, France Univ Coll London, Inst Child Hlth, Ctr Paediat Epidemiol, London WC1E 6BT, England NYU, Sch Med, N Shore Univ Hosp, Div Immunol,Dept Pediat, Manhasset, NY USA VA Puget Sound Hlth Care Syst, Seattle, WA USA DIBIT San Raffaele Sci Inst, Viral Evolut & Transmiss Unit, Milan, Italy NCI, HIV Clin Interface Lab, NIH, Frederick, MD 21701 USA Hosp Pediat JP Garrahan, Lab Biol Celular & Retrovirus, Buenos Aires, DF, Argentina Ioannidis JPA Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece
    1. Year: 2003
  2. Journal: Aids
    1. 17
    2. 11
    3. Pages: 1631-1638
  4. Type of Article: Article
  1. Abstract:

    Objective: Among perinatally infected children, the effects of certain alleles of the CCR5 and CCR2 genes on the rate of disease progression remain unclear. We addressed the effects of CCR5-Delta32 and CCR2-641 in an international meta-analysis. Methods: Genotype data were contributed from 10 studies with 1317 HIV-1-infected children (7263 person-years of follow-up). Time-to-event analyses were performed stratified by study and racial group. Endpoints included progression to clinical AIDS, death, and death after the diagnosis of clinical AIDS. The time-dependence of the genetic effects was specifically investigated. Results: There was large heterogeneity in the observed rates of disease progression between different cohorts. For progression to clinical AIDS, both CCR5-Delta32 and CCR2-641 showed overall non-significant trends for protection [hazard ratios 0.84, 95% confidence interval (0) 0.58-1.23; and 0.87, 95% CI 0.67-1.14, respectively]. However, analyses of survival showed statistically significant time- dependence. No deaths occurred among CCR5-Delta32 carriers in the first 3 years of life, whereas there was no protective effect (hazard ratio 0.95; 95% CI 0.43-2.10) in later years (P = 0.01 for the time-dependent model). For CCR2-641, the hazard ratio for death was 0.69 (95% CI 0.39-1.21) in the first 6 years of life and 2.56 (95% CI 1.26-5.20) in subsequent years (P < 0.01 for the time-dependent model). CCR5-Delta32 and CCR2- 641 offered no clear protection after clinical AIDS had developed. Conclusion: The CCR5-Delta32 and CCR2-641 alelles are associated with a decreased risk of death among perinatally infected children, but only for the first years of life. (C) 2003 Lippincott Williams Wilkins.

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