Abstract
The epidemic of hepatitis C virus (HCV) infection among HIV-infected men who have sex with men (MSM) is in its second decade, but the routes of transmission remain poorly understood. We hypothesized that by pairing single genome sequencing (SGS), to enumerate infecting HCV genomes (viruses), with detailed sexual and drug histories, we could gain insight into the routes of transmission among MSM. We used SGS to analyze blood specimens from eight HIV-infected MSM who had 10 episodes of acute (seronegative) or early HCV infections. Seven of eight men reported condomless receptive anal intercourse (CRAI), six with rectal exposure to semen, and all eight denied rectal trauma or bleeding. Of the 10 HCV infections, eight resulted from transmission of a single virus; one infection resulted from transmission of either one or a few (three or four) closely-related viruses; and one infection resulted from transmission of >10 distinct viruses. The participant infected by >10 viruses reported sharing injection equipment for methamphetamine during sex. Two other participants also injected methamphetamine during sex but they did not share injection equipment and were infected by a single virus. Conclusions: Most HCV infections of HIV-infected MSM without a history of either rectal trauma or bleeding or shared injection equipment were caused by a single virus. Intra-rectal exposure to semen during CRAI is therefore likely sufficient for HCV transmission among MSM. Conversely, rectal trauma or bleeding or shared injection equipment are not necessary for HCV transmission among MSM. These results help clarify routes of HCV transmission among MSM and can therefore help guide the design of much-needed behavioral and other interventions to prevent HCV transmission among MSM.
Highlights
The epidemic of hepatitis C virus (HCV) infection among HIV-infected men who have sex with men (MSM) is in its second decade [1], the routes of HCV transmission remain poorly understood and highly controversial [2], largely for two reasons
Several studies internationally found that condomless receptive anal intercourse (CRAI) was a significant risk factor for HCV infection [3,4,6,7,9], a German study [5] found that CRAI was not a significant risk factor for HCV infection, but that frequent rectal bleeding was
To address the relatively poor understanding of and resultant controversies about the routes of HCV transmission among MSM, we built upon earlier studies that used single genome sequencing (SGS) to study routes of HIV transmission to study these HCV transmissions
Summary
The epidemic of hepatitis C virus (HCV) infection among HIV-infected men who have sex with men (MSM) is in its second decade [1], the routes of HCV transmission remain poorly understood and highly controversial [2], largely for two reasons. Several studies internationally found that condomless receptive anal intercourse (CRAI) was a significant risk factor for HCV infection [3,4,6,7,9], a German study [5] found that CRAI was not a significant risk factor for HCV infection, but that frequent rectal bleeding was. As is the case with HIV, HCV is present in semen [10,11] and rectal fluid [12, 13], which are deposited in the rectum of MSM during sex. For sexual transmission of HCV to occur, HCV deposited in the rectum would need to cross a disrupted rectal mucosal barrier to enter the portal and/or systemic venous system. To better understand the mechanisms of sexual transmission of HCV it is necessary to functionally characterize the rectal mucosal disruption during sex
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