Effects of <i>CCR5-Δ 32</i>, <i>CCR2-64I</i>, and <i>SDF-1 3′A</i> Alleles on HIV-1 Disease Progression: An International Meta-Analysis of Individual-Patient Data

BackgroundStudies relating certain chemokine and chemokine receptor gene alleles with the outcome of HIV-1 infection have yielded inconsistent results.ObjectiveTo examine postulated associations of genetic alleles with HIV-1 disease progression.DesignMeta-analysis of individual-patient data.Setting19 prospective cohort studies and case-control studies from the United States, Europe, and Australia.PatientsPatients with HIV-1 infection who were of European or African descent.MeasurementsTime to AIDS, death, and death after AIDS and HIV-1 RNA level at study entry or soon after seroconversion. Data were combined with fixed-effects and random-effects models.ResultsBoth the CCR5-Delta32 and CCR2-64I alleles were associated with a decreased risk for progression to AIDS (relative hazard among seroconverters, 0.74 and 0.76, respectively; P = 0.01 for both), a decreased risk for death (relative hazard among seroconverters, 0.64 and 0.74; P 0.5 for all).ConclusionsThe CCR5-Delta32 and CCR2-64I alleles had a strong protective effect on progression of HIV-1 infection, but SDF-1 3'A homozygosity carried no such protection.