The estimated impact of the CCR-5 delta32 gene deletion on HIV disease progression varies with study design. Oslo HIV Cohort Study Group.
OBJECTIVE
To study the impact of the genotype CCR-5 wild-type +/A32 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 +/delta32 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 +/delta32 (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.
Eskild
A
A
Section of Epidemiology, National Institute of Public Health, Oslo, Norway.
Jonassen
T O
TO
Heger
B
B
Samuelsen
S O
SO
Grinde
B
B
D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology / Q000503:physiopathology; D000328:Adult; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D015658:HIV Infections / Q000453:epidemiology / Q000503:physiopathology*; D006801:Humans; D015994:Incidence; D008297:Male; D015995:Prevalence; D011446:Prospective Studies; D019713:Receptors, CCR5 / Q000235:genetics*; D012107:Research Design; D012189:Retrospective Studies
D019713:Receptors, CCR5