The estimated impact of the CCR-5 Δ32 gene deletion on HIV disease progression varies with study design

Objectives: To study the impact of the genotype CCR-5 wild-type +/Delta 32 on the progression rate to AIDS and death, and to discuss sources of bias according to study design. Methods: A prospective study of 310 HIV-positive subjects with follow-up time from study entry (prevalent cohort), and a prospective study of 105 HIV-positive subjects with well-defined time of HIV seroconversion, with follow-up time from the retrospectively assessed date of HIV seroconversion (retrospective incident cohort). Results: Slower progression to AIDS among subjects with CCR-5 +/Delta 32 than those with CCR-5 +/+ genotype was estimated in the prevalent cohort (P = 0.07, log-rank test). Slower progression to death from any cause was also estimated for subjects with CCR-5 +/Delta 32 (P < 0.05, log-rank test). No differences in survival after AIDS diagnosis were seen (P = 0.89, log-rank test). No differences in the progression rate to AIDS (P = 0.82, log-rank test) or death (P = 0.78, log-rank test) were estimated in the retrospective incident cohort. Conclusions: The varying estimates of the impact of CCR-5 genotype on progression to AIDS in this and other studies, may be real and reflect differences in the dependence of HIV on the CCR-5 receptor, or may be due to systematic errors caused by study design. Several methodological difficulties occur when the factor studied, such as CCR-5 genotype, is associated both with the risk of being HIV-infected and the progression of disease. (C) 1998 Lippincott Williams & Wilkins.