Journal Article

<i>CCL3L1</i> Copy Number Is a Strong Genetic Determinant of HIV Seropositivity in Caucasian Intravenous Drug Users

Kristi Huik, Maarja Sadam, Tõnis Karki, Radko Avi, Tõnu Krispin, Piret Paap, Kristi Rüütel, Anneli Uusküla, Ave Talu, Katri Abel-Ollo and Irja Lutsar

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 201, issue 5, pages 730-739
Published in print March 2010 | ISSN: 0022-1899
Published online March 2010 | e-ISSN: 1537-6613 | DOI: http://dx.doi.org/10.1086/650491
CCL3L1 Copy Number Is a Strong Genetic Determinant of HIV Seropositivity in Caucasian Intravenous Drug Users

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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 (>2) was associated with an 80% reduced risk of acquiring HIV infection after adjusting for age, sex, HCV and HBV status, CCR5-Δ32 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.

Journal Article.  4650 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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