THE ESTIMATED IMPACT OF THE CCR-5 DELTA-32 GENE DELETION ON HIV DISEASE PROGRESSION VARIES WITH STUDY DESIGN

Objectives: To study the impact of the genotype CCR-5 wild-type +/Delt a 32 on the progression rate to AIDS and death, and to discuss sources of bias according to study design. Methods: A prospective study of 31 0 HIV-positive subjects with follow-up time from study entry (prevalen t cohort), and a prospective study of 105 HIV-positive subjects with w ell-defined time of HIV seroconversion, with follow-up time from the r etrospectively assessed date of HIV seroconversion (retrospective inci dent cohort). Results: Slower progression to AIDS among subjects with CCR-5 +/Delta 32 than those with CCR-5 +/+ genotype was estimated in t he prevalent cohort (P = 0.07, log-rank test). Slower progression to d eath 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 d iagnosis were seen (P = 0.89, log-rank test). No differences in the pr ogression rate to AIDS (P = 0.82, log-rank test) or death (P = 0.78, l og-rank test) were estimated in the retrospective incident cohort. Con clusions: The varying estimates of the impact of CCR-5 genotype on pro gression to AIDS in this and other studies, may be real and reflect di fferences in the dependence of HIV on the CCR-5 receptor, or may be du e 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 progressi on of disease. (C) 1998 Lippincott Williams & Wilkins.