Clustering of HCV coinfections on HIV phylogeny indicates domestic and sexual transmission of HCV.
BACKGROUND
HCV coinfection remains a major cause of morbidity and mortality among HIV-infected individuals and its incidence has increased dramatically in HIV-infected men who have sex with men(MSM).


METHODS
Hepatitis C virus (HCV) coinfection in the Swiss HIV Cohort Study(SHCS) was studied by combining clinical data with HIV-1 pol-sequences from the SHCS Drug Resistance Database(DRDB). We inferred maximum-likelihood phylogenetic trees, determined Swiss HIV-transmission pairs as monophyletic patient pairs, and then considered the distribution of HCV on those pairs.


RESULTS
Among the 9748 patients in the SHCS-DRDB with known HCV status, 2768(28%) were HCV-positive. Focusing on subtype B(7644 patients), we identified 1555 potential HIV-1 transmission pairs. There, we found that, even after controlling for transmission group, calendar year, age and sex, the odds for an HCV coinfection were increased by an odds ratio (OR) of 3.2 [95% confidence interval (CI) 2.2, 4.7) if a patient clustered with another HCV-positive case. This strong association persisted if transmission groups of intravenous drug users (IDUs), MSMs and heterosexuals (HETs) were considered separately(in all cases OR>2). Finally we found that HCV incidence was increased by a hazard ratio of 2.1 (1.1, 3.8) for individuals paired with an HCV-positive partner.


CONCLUSIONS
Patients whose HIV virus is closely related to the HIV virus of HIV/HCV-coinfected patients have a higher risk for carrying or acquiring HCV themselves. This indicates the occurrence of domestic and sexual HCV transmission and allows the identification of patients with a high HCV-infection risk.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland roger.kouyos@uzh.ch.
Roger D
RD
Kouyos
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Andri
A
Rauch
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Jürg
J
Böni
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Sabine
S
Yerly
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Cyril
C
Shah
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Vincent
V
Aubert
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Thomas
T
Klimkait
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Helen
H
Kovari
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Alexandra
A
Calmy
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Matthias
M
Cavassini
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Manuel
M
Battegay
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Pietro L
PL
Vernazza
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Enos
E
Bernasconi
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Bruno
B
Ledergerber
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland, Institute of Medical Virology, University of Zurich, Zurich, Switzerland, Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland, Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland, Department Biomedicine, University of Basel, Basel, Switzerland, Division of Infectious Diseases, Geneva University Hospital, Geneva, Division of Immunology, University Hospital Lausanne, Lausanne, Switzerland, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland and Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Huldrych F
HF
Günthard
D003062:Codon; D015331:Cohort Studies; D060085:Coinfection / Q000453:epidemiology* / Q000235:genetics / Q000635:transmission; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000235:genetics / Q000635:transmission; D015497:HIV-1 / Q000235:genetics*; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000453:epidemiology* / Q000235:genetics / Q000635:transmission; D018451:Homosexuality, Male / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015819:Substance Abuse, Intravenous / Q000453:epidemiology; D013557:Switzerland
D003062:Codon; D012367:RNA, Viral
HIV-HCV coinfection; genotypic resistance testing; molecular epidemiology; sexual transmission of HCV