Disease Progression to Clinical AIDS

Background. A mean of 9–10 years of human immunodeficiency virus type 1 (HIV-1) infection elapse before clinical AIDS develops in untreated persons, but this rate of disease progression varies substantially among in-dividuals. To investigate host genetic determinants of the rate of progression to clinical AIDS, we performed a multistage genomewide association study. Methods. The discovery stage comprised 156 individuals from the Multicenter AIDS Cohort Study, enriched with rapid and long-term nonprogressors to increase statistical power. This was followed by replication tests of putatively associated genotypes in an independent population of 590 HIV-1–infected seroconverters. Results. Significant associations with delayed AIDS progression were observed in a haplotype located at 1q41, 36 kb upstream of PROX1 on chromosome 1 (relative hazard ratio, 0.69; Fisher’s combined).7Pp 6.23 1