1066 
HCV Spreads among HIV+ Men Who Have Sex with Men: Evidence of Separate Sexual Transmission Networks in Europe and Australia
Thijs van de Laar*1, M Danta2,3, S Bhagani2, M L Chaix4, G Dore3, M Nelson5, M Prins1,6, M Vogel7, P White3, R Coutinho1,6,8, and HIV and Acute HCV group
1Hlth Svc, Amsterdam, The Netherlands; 2Royal Free and Univ Coll London, UK; 3Univ of New South Wales, Sydney, Australia; 4Hosp Necker, Paris France; 5Chelsea and Westminster Hosp, London, UK; 6Academic Med Ctr, Amsterdam, The Netherlands; 7Univ of Bonn, Germany; and 8Natl Inst of Publ Hlth and the Environment, The Netherlands
Background: Rising hepatitis C virus (HCV) incidence
rates among HIV+ men who have sex with men (MSM) in Europe have been
reported since 2000, and are associated with high-risk sexual behavior. To
investigate whether sexual transmission of HCV among HIV+ MSM is
restricted to small city-bound outbreaks or whether a large-scale European
sexual HCV transmission network exists, a phylogenetic study was conducted.
Methods: We enrolled 224 HIV+ MSM diagnosed
with acute HCV infection from England (n = 107), the Netherlands (n
= 58), Germany (n = 24), France (n = 11), and Australia (n
= 24). Part of the HCV NS5B region (436 bp) was amplified and sequenced. Maximum
likelihood phylogenies were constructed using PAUP* (HKY-Г substitution
model), comparing MSM cases with unrelated NS5B sequences. Date of origin for each
MSM-specific HCV cluster will be estimated using a molecular clock approach.
Results: In total, 200 (89%) of 224 NS5B sequences
were obtained. Circulating HCV strains were of subtype 1a (60%), 4d (23%), 3a
(10%), 1b (5%), and 2b/c (3%). Phylogenetic analysis revealed 12 distinct MSM-specific
HCV clusters of mainly subtype 1a and 4d, containing 3 to 37 sequences each (bootstrap
values >70%) covering 160 (80%) of the sequences. Of 6 larger clusters, 5 (>10
sequences), contain sequences from more than 1 European country. In contrast,
country-specific clusters tend to be smaller (<10 sequences) or are Australian.
Despite a high degree of clustering within the continents of Europe and
Australia, mixing between both continents was seldom observed.
Conclusions: Current phylogenetic analysis reveals 2
recently evolved networks of ongoing HCV transmission among HIV+ MSM,
one in Europe, presumably linked to traveling associated with sexual high-risk
behavior, and a separate one in Australia. Co-circulating HCV lineages of
different genotypes suggest (behavioral) change of the host rather than
intrinsic viral evolution of the virus itself. International mixing of
sequences increases with cluster size emphasizing the rapid spread of regional
outbreaks to neighboring countries. Targeted prevention and implementation of frequent
HCV screening in HIV+ MSM is needed to deter further spread of this
emerging sexually transmitted infection, especially because 90% of HIV/HCV-co-infected
MSM harbor strains of difficult-to-treat HCV genotypes 1 and 4.
|
