Despina Contopoulos-Ioannidis, MD

Publication Details

  • Effects of CCR5-Delta 32 and CCR2-64I alleles on disease progression of perinatally HIV-1-infected children: an international meta-analysis AIDS Ioannidis, J. P., 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. 2003; 17 (11): 1631-1638

    Abstract:

    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 CCR2-64I in an international meta-analysis.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.There was large heterogeneity in the observed rates of disease progression between different cohorts. For progression to clinical AIDS, both CCR5-delta32 and CCR2-64I showed overall non-significant trends for protection [hazard ratios 0.84, 95% confidence interval (CI) 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 CCR2-64I, 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 CCR2-64I offered no clear protection after clinical AIDS had developed.The CCR5-delta32 and CCR2-64I alleles are associated with a decreased risk of death among perinatally infected children, but only for the first years of life.

    View details for DOI 10.1097/01.aids.0000060411.18106.0f

    View details for Web of Science ID 000184661800007

    View details for PubMedID 12853745

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