CCR5 expression and duration of high risk sexual activity among HIV-seronegative men who have sex with men.
OBJECTIVE
To test the hypothesis that in comparison with those with shorter risk duration, individuals with longer HIV risk duration would have reduced susceptibility to HIV-1 infection as measured by CCR5 expression, and to evaluate whether variation in CCR5 expression could be explained by known genetic polymorphisms.


METHODS
A cross-sectional study of HIV-1 exposed but uninfected men who have sex with men. The risk duration was estimated from self-reported years since first receptive anal intercourse. CCR5 expression on peripheral blood CD4+ monocytes and T cells was determined by flow cytometry. The CCR5-Delta32 mutation and polymorphisms in the CCR5 promoter and CCR2 as well as the copy number of CCL3L1 were analyzed by polymerase chain reaction. Plasma levels of MIP-1alpha (CCL3), MIP-1beta (CCL4) and RANTES (CCL5) were also measured. As risk duration varied with age, analyses were restricted to 67 individuals aged 30-49 years.


RESULTS
Multiple linear regression analyses, adjusted for age and race, showed a significant negative association between HIV risk duration and CCR5 expression on monocytes (P = 0.01), and in a separate model, a similar negative association with CCR5 expression on T cells (P = 0.03). Low CCR5 expression was attributable mainly to CCR5-Delta32 heterozygosity and the CCR5-59029G allele.


CONCLUSIONS
We confirmed a role for reduced CCR5 expression in HIV-1 resistance. CCR5-Delta32 heterozygosity and the CCR5-59029G allele were significant predictors of low CCR5 expression. Individuals with high CCR5 expression who resisted infection despite long HIV risk duration form an interesting group within which to search for additional mechanisms of resistance to HIV infection.
Thomas
Susan M
SM
Department of Environmental Medicine, New York University School of Medicine, NY 10016-3240, USA
Tse
Doris B
DB
Ketner
D Scott
DS
Rochford
Gemma
G
Meyer
Daniel A
DA
Zade
David D
DD
Halkitis
Perry N
PN
Nádas
Arthur
A
Borkowsky
William
W
Marmor
Michael
M
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D003430:Cross-Sectional Studies; D005838:Genotype; D018023:HIV Seronegativity / Q000502:physiology*; D015497:HIV-1; D018451:Homosexuality, Male / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry; D019713:Receptors, CCR5 / Q000032:analysis* / Q000235:genetics; D012309:Risk-Taking; D012725:Sexual Behavior; D013997:Time Factors
D019713:Receptors, CCR5