Dominant Effects of CCR2-CCR5 Haplotypes in HIV-1 Disease Progression
Journal of Acquired Immune Deficiency Syndromes
AIDS, CCR2, CCR5, Haplotype, HIV, Disease progression
Three haplotypes for the CCR2–CCR5 region previously have been shown to affect AIDS progression; however, it is not known if the protective and accelerating effects of the haplotypes are relatively constant throughout infection or exert their effects early or late in HIV type 1 infection. The authors report the relative contributions to AIDS progression of CCR2 64I, CCR5Δ32, and the CCR5 promoter haplotype +.P1.+ in the GRIV cohort, which included patients representing the extremes of the distribution for AIDS progression: rapid progressors (RP) who developed CD4+ T-cell counts of <300/ mm3 within 3 years after the last HIV-1–seronegative test and slow progressors (SP) who were HIV-1 infected for 8 years with CD4+ T-cell counts of >500/mm3. Comparing the RP with a seroconverter control group including intermediate progressors to AIDS, we observed the early protective effect of CCR5Δ32 (odds ratio = 0.25; P = 0.007) was similar in strength to the early susceptible effect of CCR5 +.P1.+ (odds ratio = 2.1, P = 0.01). Comparison of the intermediate control group to the SP showed weaker and less significant odd ratios, suggesting that the effect of these factors tended to be stronger on early progession; the tendency towards a disproportionately early effect was significant for CCR5Δ32 (P = 0.04) but not for CCR5 +.P1.+ (P = 0.12). Follow-up of SP demonstrated that these polymorphisms have little effect after 8 years, because the subset of SP who had progression after study entry had the same genotype distribution as the global population of SP, suggesting that factors other than CCR5 or CCR2 genetic variants must be responsible for the longterm maintenance of nonprogression.
Winkler, Cheryl; Houria Hendel; Mary Carrington; Michael W. Smith; George W. Nelson; Stephen J. O'Brien; John Phair; David Vlahov; Lisa Jacobson; Jay Rappaport; Alexandre Vasilescu; Sebastien Berlin-Maghit; Ping An; Wei Lu; Jean-Marie Andrieu; Francois Schachter; Amu Therwath; and Jean-Francois Zagury. 2004. "Dominant Effects of CCR2-CCR5 Haplotypes in HIV-1 Disease Progression." Journal of Acquired Immune Deficiency Syndromes 37, (4): 1534-1538. http://nsuworks.nova.edu/cnso_bio_facarticles/560