Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 201, Issue 5, Pages 730-739Publisher
OXFORD UNIV PRESS INC
DOI: 10.1086/650491
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Funding
- European Regional Development Fund [SFOS WP1-NeuroAIDS]
- Estonian Science Foundation [8004]
- Basic Financing and the Target Financing of Estonian Ministry of Education and Research [SF0182726s06]
- European Commission [2005305]
- Global Fund
- National HIV/AIDS Strategy
- US Civilian Research Development Foundation [ESX0-2722-TA-06]
- US National Institutes of Health, National Institute on Drug Abuse [R01DA03574]
- European Union
- Archimedes Foundation
- Norwegian Financial Mechanism/EEA [EE0016]
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Background. A high copy number of CCL3L1, the most potent human immunodeficiency virus (HIV) suppressive chemokine, associates with reduced HIV susceptibility. Whether CCL3L1 influences acquisition of multiple blood-borne infections (eg, hepatitis C virus [HCV], HIV, and hepatitis B virus [HBV] infections), which occur commonly among injection drug users (IDUs), is unknown. Methods. We determined CCL3L1 copy number by real-time polymerase chain reaction among 374 Caucasian IDUs from Estonia; 285 were HCV positive, 208 were HIV positive, 177 were HCV and HIV positive, and 57 were HCV and HIV negative. Results. In univariate and multivariate analyses, HCV and HBV seropositivity and duration of IDU each strongly predicted HIV seropositivity. A high CCL3L1 copy number (12) was associated with an 80% reduced risk of acquiring HIV infection after adjusting for age, sex, HCV and HBV status, CCR5-D32 polymorphism, and IDU duration (odds ratio, 0.20; 95% confidence interval, 0.09-0.45). By contrast, CCL3L1 gene dose did not influence HCV seropositivity. Among HCV-positive IDUs, there was a 3.5-fold overrepresentation and 65% underrepresentation of a high CCL3L1 copy number among HCV-positive, HIV-negative subjects and HCV-positive, HIV-positive subjects, respectively. Conclusion. Among IDUs with extensive exposure to HCV and HIV, CCL3L1 copy number is a major determinant of HIV seropositivity but not of HCV seropositivity. The contrasting distribution of a protective high CCL3L1 copy number among HCV-positive, HIV-negative IDUs versus HCV-positive, HIV-positive IDUs may reflect that HIV preferentially selects for subjects with a low CCL3L1 gene dose.
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