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Chemokine receptor genotypes and HIV disease progression: a preliminary meta-analysis.
Ioannidis JP; Contopoulos-Ioannidis DG; HIVRB-NIAID, Bethesda, MD 20892,
December 30, 1998
Int Conf AIDS. 1998;12:148 (abstract no. 13311). Unique Identifier :

OBJECTIVE: To evaluate whether chemokine receptor genotypes including heterozygosity for the CCR5 32-bp deletion (CCR5 delta 32) and the presence of the CCR 64I mutation affect the rate of disease progression to AIDS (1993 CDC definition) among HIV-infected patients. METHODS: Preliminary meta-analysis of 8 cohorts with n = 2,741 patients with known CCR5 genotype (45% seroconverters [SC]) and 6 cohorts with n = 2,089 patients with known CCR2 genotype (43% SC). Due to measurement error, it was anticipated that the observed strength of associations should be attenuated among seroprevalent (SP) patients, therefore SP patients were analyzed separately from SC. RESULTS: Heterozygosity for CCR5 delta 32 conferred a highly significant protective effect (odds ratio 0.69 [95% CI, 0.61-0.79] by fixed effects, 0.68 [95%, 0.58-0.80] by random effects) with borderline heterogeneity (0.1 < p < 0.2) between cohorts. As expected, the benefit was more clear among SC (odds 0.65 [0.53-0.80]) than among SP patients (odds 0.73 [0.61-0.86]). CCR2 641 did not confer overall a statistically significant protective effect (odds ratio 0.93 [0.81-1.06]; no heterogeneity t2 = 0]), although the more accurate SC cohorts showed a more clear protection (odds ratio 0.80 [0.65-0.99]; SP cohorts odds ratio 1.03 [0.86-1.23]). The size-weighted difference in early viral load between CCR5 wild-type homozygotes and heterozygotes was a 2.5 fold lower median viral load in the latter group which translates to an odds ratio of 0.7 for disease progression. CONCLUSIONS: CCR5 delta 32 heterozygosity offers a protective benefit for disease progression which is at least partially mediated through an effect on viral load. The evidence for CCR2 64I is ambiguous, ranging from a sizable effect to no effect at all. To avoid a posteriori selective reporting and subgroup analyses which may yield misleading results, investigators in the field are invited to contribute data to this ongoing international collaborative meta-analysis.

MEETING ABSTRACTS META-ANALYSIS Cohort Studies Disease Progression Genotype Heterozygote Homozygote Human HIV Infections/*EPIDEMIOLOGY/GENETICS Receptors, Chemokine/*GENETICS Receptors, CCR5/GENETICS Viral Load

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