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


CONCLUSIONS
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.
Huik
Kristi
K
Department of Microbiology, Faculty of Medicine, University of Tartu, 50411 Tartu, Estonia.
Sadam
Maarja
M
Karki
Tõnis
T
Avi
Radko
R
Krispin
Tõnu
T
Paap
Piret
P
Rüütel
Kristi
K
Uusküla
Anneli
A
Talu
Ave
A
Abel-Ollo
Katri
K
Lutsar
Irja
I
D000328:Adult; D019742:Chemokines, CC / Q000235:genetics*; D055030:Drug Users; D004957:Estonia; D005260:Female; D018628:Gene Dosage; D006679:HIV Seropositivity / Q000235:genetics* / Q000276:immunology*; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D015819:Substance Abuse, Intravenous; D044465:White People
C492767:CCL3L1 protein, human; D019742:Chemokines, CC