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Chemokine receptor genotypes and HIV disease progression: a preliminary meta-analysis.




 

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



 




Information in this article was accurate in December 30, 1998. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.