CCL3L1 copy number is a strong genetic determinant of HIV seropositivity in Caucasian intravenous drug users.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Huik, Kristi; Sadam, Maarja; Karki, Tõnis; Avi, Radko; Krispin, Tõnu; Paap, Piret; Rüütel, Kristi; Uusküla, Anneli; Talu, Ave; Abel-Ollo, Katri; Lutsar, Irja
Year of Publication: 2010
Journal: J Infect Dis
Volume: 201
Issue: 5
Pagination: 730-9
Date Published: 2010 Mar
Publication Language: eng
ISSN: 1537-6613
Keywords: Adult, Chemokines, CC, Drug Users, Estonia, European Continental Ancestry Group, Female, Gene Dosage, Hepacivirus, Hepatitis C, HIV Seropositivity, Humans, Immunity, Innate, Male, Polymerase Chain Reaction, Substance Abuse, Intravenous

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-Delta32 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.

DOI: 10.1086/650491
Alternate Journal: J. Infect. Dis.