Dataset Information

Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men.

ABSTRACT: BACKGROUND & AIMS:Since 2000, there has been a marked rise in acute hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). We conducted an international phylogenetic study to investigate the existence of an HCV transmission network among MSM. METHODS:HIV-positive MSM diagnosed with recent HCV (n = 226) in England (107), The Netherlands (58), France (12), Germany (25), and Australia (24) between 2000 and 2006 were enrolled into a molecular phylogenetic study. Using real-time polymerase chain reaction (PCR), the NS5B region of the HCV genome (436 base pair) was amplified, sequenced, and compared with unrelated NS5B sequences. RESULTS:NS5B sequences were obtained from 200 (89%) cases. Circulating HCV genotypes were 1a (59%), 4d (23%), 3a (11%), 1b (5%), and 2b/c (3%). Phylogenetic analysis revealed 156 (78%) sequences that formed 11 clusters (bootstrap value > 70%) containing between 4 and 37 individual sequences. Country mixing was associated with larger cluster size (17 vs 4.5 sequences; P = .03). "Molecular clock" analysis indicated that the majority (85%) of transmissions occurred since 1996. CONCLUSIONS:Phylogenetic analysis revealed a large international network of HCV transmission among HIV-positive MSM. The rapid spread of HCV among neighboring countries is supported by the large proportion (74%) of European MSM infected with an HCV strain co-circulating in multiple European countries, the low evolutionary distances among HCV isolates from different countries, and the trend toward increased country mixing with increasing cluster size. Temporally, this epidemic coincides with the introduction of highly active antiretroviral therapy and associated increases in sexual risk behaviors. International collaborative public health efforts are needed to mitigate HCV transmission among this population.

SUBMITTER: van de Laar T

PROVIDER: S-EPMC4260925 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men.

van de Laar Thijis T Pybus Oliver O Bruisten Sylvia S Brown David D Nelson Mark M Bhagani Sanjay S Vogel Martin M Baumgarten Alex A Chaix Marie-Laure ML Fisher Martin M Gotz Hannelore H Matthews Gail V GV Neifer Stefan S White Peter P Rawlinson William W Pol Stanislav S Rockstroh Jurgen J Coutinho Roel R Dore Greg J GJ Dusheiko Geoffrey M GM Danta M M

Gastroenterology 20090501 5

<h4>Background & aims</h4>Since 2000, there has been a marked rise in acute hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). We conducted an international phylogenetic study to investigate the existence of an HCV transmission network among MSM.<h4>Methods</h4>HIV-positive MSM diagnosed with recent HCV (n = 226) in England (107), The Netherlands (58), France (12), Germany (25), and Australia (24) between 2000 and 2006 were enrolled into a mol ...[more]

PMID: 19422083

Similar Datasets

Project description:During primary HIV infection, the presence of minority drug resistance mutations (DRM) may be a consequence of sexual transmission, de novo mutations, or technical errors in identification. Baseline blood samples were collected from 24 HIV-infected antiretroviral-naive, genetically and epidemiologically linked source and recipient partners shortly after the recipient's estimated date of infection. An additional 32 longitudinal samples were available from 11 recipients. Deep sequencing of HIV reverse transcriptase (RT) was performed (Roche/454), and the sequences were screened for nucleoside and nonnucleoside RT inhibitor DRM. The likelihood of sexual transmission and persistence of DRM was assessed using Bayesian-based statistical modeling. While the majority of DRM (>20%) were consistently transmitted from source to recipient, the probability of detecting a minority DRM in the recipient was not increased when the same minority DRM was detected in the source (Bayes factor [BF] = 6.37). Longitudinal analyses revealed an exponential decay of DRM (BF = 0.05) while genetic diversity increased. Our analysis revealed no substantial evidence for sexual transmission of minority DRM (BF = 0.02). The presence of minority DRM during early infection, followed by a rapid decay, is consistent with the "mutation-selection balance" hypothesis, in which deleterious mutations are more efficiently purged later during HIV infection when the larger effective population size allows more efficient selection. Future studies using more recent sequencing technologies that are less prone to single-base errors should confirm these results by applying a similar Bayesian framework in other clinical settings.IMPORTANCE The advent of sensitive sequencing platforms has led to an increased identification of minority drug resistance mutations (DRM), including among antiretroviral therapy-naive HIV-infected individuals. While transmission of DRM may impact future therapy options for newly infected individuals, the clinical significance of the detection of minority DRM remains controversial. In the present study, we applied deep-sequencing techniques within a Bayesian hierarchical framework to a cohort of 24 transmission pairs to investigate whether minority DRM detected shortly after transmission were the consequence of (i) sexual transmission from the source, (ii) de novo emergence shortly after infection followed by viral selection and evolution, or (iii) technical errors/limitations of deep-sequencing methods. We found no clear evidence to support the sexual transmission of minority resistant variants, and our results suggested that minor resistant variants may emerge de novo shortly after transmission, when the small effective population size limits efficient purge by natural selection.

Dataset Information

Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men.

Publications

Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets