Whether hepatitis C virus (HCV) is sexually transmitted has been a contentious issue from before HCV was identified in 1989 as the cause of non–A, non–B hepatitis.1 Although studies performed shortly after the discovery of HCV demonstrated that HCV seropositivity was associated with having multiple heterosexual partners,2,3 multiple subsequent prospective cohort studies with stable heterosexual couples discordant for HCV infection showed no intercouple transmissions.4–6 The lack of HCV transmission between stable sex partners in these studies convinced most researchers that sexual transmission of HCV did not occur.
Similar to the issue of heterosexual transmission, whether HCV is sexually transmitted among men who have sex with men (MSM) has also been controversial. Studies among MSM from the 1990s through mid-2000s found no association between HCV transmission and sexual behavior.7–10 However, the situation among HIV-infected MSM seems to be different. The first 2 reports of possible sexual transmission of HCV were case series from Northern Europe in 2004 of HIV-infected MSM with incident HCV who had antecedent syphilis infection and no history of injection drug use.11,12 These studies were followed by case-control studies from Europe13–15 and the United States16,17 showing associations between acquisition of HCV and sexual practices among MSM, specifically unprotected receptive anal intercourse and fisting.
The article by Breskin et al.18 in this issue of STD provides further evidence of sexual transmission of HCV among HIV-infected MSM. Through mandatory laboratory reporting of HIV and the demographic data derived from the initial investigation of these cases, researchers from the New York City Department of Health and Mental Hygiene identified 41,303 MSM who were diagnosed as having HIV before 2010, did not engage in injection drug use at the time of their HIV diagnosis, were alive after 2000, and did not have an HCV diagnosis at the time of or 3 months after HIV diagnosis. The case-patients were linked to HCV surveillance data which then identified 2016 subsequent HCV infections in these men. This large number of incident infections corresponds to a cumulative incidence rate of 4.9%, more than 3 times higher than has been previously reported for MSM who do not inject drugs.19 In addition, they linked the patients to sexually transmitted infection (STI) surveillance data, specifically data on syphilis, gonorrhea, and chlamydia. They found an association between incident HCV and syphilis infection in the year before the diagnosis of HCV (risk ratio, 1.9). This result further confirms 2 previous studies that also used laboratory-confirmed STI (rather than relying on recall by patients) that had found an association between STI diagnosed in the 6 to 12 months before diagnosis of acute HCV among HIV-infected MSM.15,17 This documentation of an STI acquired before HCV provides a strong link between sexual behaviors and acquisition of HCV.
The most striking finding of the study by Breskin et al,18 however, is the 2016 incident cases of HCV detected in HIV-infected MSM during the first decade of 2000 in New York City, the largest number of incident cases reported in any cohort world-wide. Although their calculated incidence rate of 6 per 1000 person-years is not higher than those reported in other cohorts in the US17 and other countries,20–22 because this was a population-based study, the denominator was huge—nearly 42,000 HIV-infected MSM, demonstrating how powerful this approach is in estimating the magnitude of the healthcare challenge for diagnosis and treatment of these men. We therefore agree with the authors in applauding the Centers for Disease Control and Prevention for now officially recommending improved surveillance for incident HCV through more frequent HCV antibody testing in sexually active HIV-infected MSM.23 Quarterly screening for increased alanine aminotransferase (ALT), an enzyme highly specific for hepatocellular damage, however, is more sensitive than screening with antibody testing.24,25 After incident HCV infection, ALT increases weeks to months before antibody production, which is especially true in HIV-infected patients.24,25 Our screening practice is therefore to perform quarterly ALT testing followed by confirmatory HCV viral load and antibody testing for any new ALT elevation in HIV-infected MSM at high risk for HCV. Earlier diagnosis has led to treatment in the acute phase with a very high success rate,26 and with the availability of sofosbuvir-based regimens, this treatment will be both safer and more effective, providing another tool to slow the advance of this epidemic by both decreasing the duration of viremia as well as the number of viremic men.
One important missing piece of data from this study by Breskin et al.18 is whether the incidence rate in New York City was increasing over this 11-year period, as has been found in most cohorts that have assessed incidence over this same time.20–22,27 This information is crucial toward understanding the dynamics of this epidemic in New York, and we therefore hope that the New York City Department of Health and Mental Hygiene will perform further analyses of their data to publish this valuable information.
In summary, despite the multiple high-quality epidemiological studies of risk factors for acquisition of HCV among HIV-infected MSM, as well as the studies showing an association between bacterial STI and subsequent HCV infection, including Breskin et al., we do not yet understand the mechanisms of HCV transmission during the many activities that are part of sex among these HIV-infected men who acquire HCV. To accomplish this, we need to use the available epidemiological evidence to design studies to more directly test the possible routes of transmission. Such novel studies are urgently needed to develop more effective prevention strategies as part of a multipronged approach to reversing this epidemic of sexually transmitted HCV.
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