A high copy number of CCL3L1, the most potent HIV-suppressive chemokine, associates with reduced HIV susceptibility. Whether CCL3L1 influences acquisition of multiple blood-borne infections (HCV, HIV-1, HBV) that occurs commonly among intravenous drug users (IDUs) is unknown.
We determined CCL3L1 copy number by real-time PCR among 374 Caucasian IDUs from Estonia of whom 285 were HCV-positive, 208 HIV+, 177 HCV+/HIV+, and 57 HCV−/HIV−.
In univariate and multivariate analyses, HCV and HBV seropositivity, and duration of IDU each strongly predicted HIV seropositivity. A high CCL3L1 copy number (>2) associated with a 80% reduced risk of acquiring HIV, after adjusting for age, gender, HCV/HBV status, CCR5-Δ32 polymorphism and IDU duration (OR=0.20; 95% CI=0.09–0.45). By contrast, CCL3L1 gene dose did not influence HCV seropositivity. Among HCV+ IDUs, there was a 3.5-fold over- and 65% under-representation of a high CCL3L1 copy number among HCV+/HIV− and HCV+/HIV+ subjects, respectively.
Among IDUs exposed heavily to HCV/HIV, CCL3L1 copy number is a major determinant of HIV seropositivity, but not HCV seropositivity. The contrasting distribution of a protective high CCL3L1 copy number among HCV+/HIV− vs HCV+/HIV+ IDUs may reflect that HIV preferentially selects for subjects with a low CCL3L1 gene dose.