Studies Shed Light on Hepatitis C Virus Sexual Transmission among Gay Men


Hepatitis C virus (HCV) transmission among HIV positive gay men has leveled off in Amsterdam -- one of the first cities with an outbreak of apparently sexually transmitted HCV infection -- and it continues to be rare among HIV negative men who have sex with men, according to recent studies. Other research looked at HCV sexual transmission among HIV positive and negative men in Switzerland, and at the association between HCV viral load in blood and semen.

Starting in the early 2000s, researchers in the U.K. and other European cities began reporting clusters of apparently sexually transmitted acute HCV infection among HIV positive men who have sex with men (MSM); similar outbreaks followed in Australia and the U.S. Recent data indicate that HCV incidence among gay men now exceeds that of injection drug users in some cities. A number of risk factors have been implicated -- including unprotected anal intercourse, fisting, group sex, other sexually transmitted infections, and non-injection recreational drug use -- but these have not been consistent across studies.

HCV in Amsterdam

At the recent EASL International Liver Congress in London, Joost Vanhommerig from the Amsterdam Public Health Service and colleagues presented an update on trends in HCV incidence among gay and bisexual men in the Amsterdam Cohort Study between 1984 and 2012.

This ongoing prospective cohort study, started in 1984, has enrolled more than 2000 HIV positive and HIV negative gay and bisexual men. In 2000-2003, HCV incidence increased more than 10-fold among HIV positive MSM in the cohort, from 0.8 per 1000 person years during 1984-1999 to 8.7 per 1000 person-years in 2000-2003, the researchers noted as background.

The current analysis included 2080 men with at least 2 study visits (after excluding 24 men found to be HCV positive at study entry), collectively contributing 17,300 person-years of follow-up data. The median age at study entry was 30 years and the median follow-up duration was 7.4 years. One-quarter (526 men) were HIV positive at study entry and 222 seroconverted during follow-up.

Among the 748 HIV positive men, 29 new HCV infections were documented. No new HCV infections were observed among the HIV negative men. HIV-related factors including HIV RNA level, use of antiretroviral therapy, and current or nadir (lowest-ever) CD4 T-cell count were not significant predictors of HCV infection.

Looking at changes in incidence between 2005 and 2010, the rate declined slightly (incidence rate ratio 0.94). This compared with a substantial increase in incidence between 2000 and 2005 (incidence rate ratio 3.41).

"The incidence of primary HCV infection among HIV+ MSM rose sharply between 2000-2005, but appears to have stabilized at around 10-12 [per 1000 person-years] thereafter," the researchers concluded. "The HIV-uninfected MSM population remains largely unaffected by this epidemic."

"Prevention efforts, screening and treatment seem to pay off," they suggested, adding that, "[a] saturation effect among those at highest risk for infection may partly explain the leveling off."

However, "while incidence of primary HCV infection may have stabilized, incidence of reinfection after HCV clearance remains high," they cautioned. "Continued efforts [are] needed to prevent the ongoing spread of HCV among HIV-infected MSM."

In a related study published in the March 13 edition of AIDS, Vanhommerig, Anouk Urbanus, and colleagues presented a 15-year overview of the HCV epidemic among MSM visiting a large sexually transmitted disease clinic in Amsterdam. Participants completed anonymous interviews and were tested for HIV and HCV twice yearly.

HCV prevalence among HIV positive MSM increased from 5.6% in 1995 to a peak of 20.9% in 2008. HCV infection was independently associated with injection drug use, unprotected anal intercourse, chlamydia, and older age. HCV infection was more strongly associated with fisting during 2007-2008 (adjusted odds ratio [OR] 2.85) than during 2009-2010 (adjusted OR 0.92).

Phylogenetic analysis showed a high degree of MSM-specific clustering from 2000 onwards, with no overlap with injection drug use clusters. (The researchers noted that the HCV epidemic among people who inject drugs in Amsterdam has been stable since the late 1990s -- before the MSM outbreak began.) Identification of a new MSM-specific HCV strain and recent infections in established clusters indicate ongoing transmission in this population.

"HCV prevalence among HIV positive MSM significantly increased over calendar time but appears to level off in recent years, possibly due to increased awareness, saturation in the population, decreased risk behavior and earlier HCV screening and treatment," the authors concluded. "The association with fisting became less strong over time, but our analyses continue to support sexual transmission."

In contrast with these findings, the most recent estimates of HCV incidence among MSM in the Swiss HIV Cohort Study and the Multicenter AIDS Cohort in 4 U.S. cities suggest that incidence is still increasing and has not yet leveled off, the researchers noted in their discussion.

Again, HCV prevalence among HIV negative men remained low, at 0.5% during 2007-1010, similar to that of the general population in Amsterdam. 5 out of 6 HCV strains from HIV negative MSM were neither closely related to strains circulating among HIV positive men nor closely related to each other. However, 1 HIV negative man was infected with an HCV strain seen in HIV positive MSM, suggesting some overlap in sexual transmission networks. "[P]otential spillover to the HIV negative community cannot yet be excluded," they authors warned.

In Amsterdam, "the leveling off of the HCV prevalence might be a result of HCV saturation in the highest risk groups. In that case, the stabilizing epidemic would be explained by a lack of susceptible individuals rather than by decreased sexual risk behavior among the population at risk," they wrote. "However, the effect of pronounced HCV risk factors such as fisting and GHB use became less strong over time, suggesting behavioral change and possibly increased awareness leading to less risky sexual practices."

HCV in Switzerland

Two related studies looked at HCV incidence among gay and bisexual men in Switzerland.

As described in the January 22 advance edition of the International Journal of Epidemiology, Roger Kouyos and fellow investigators with the Swiss HIV Cohort Study used clinical and viral genetic sequence data to assess correlations between HIV and HCV outbreaks.

Among 9748 HIV patients in the Swiss HIV Cohort Study Drug Resistance Database, 2768 (28%) were coinfected with HCV and 208 (2%) showed evidence of recent HCV infection. Looking at 1555 potential HIV transmission pairs -- determined by genetic similarity between viruses -- they found that the risk of HCV coinfection increased by more than 3-fold (OR 3.2) if an individual clustered with another person with HCV. Furthermore, HCV incidence doubled (hazard ratio 2.1) for initially HCV negative individuals paired with an HCV positive partner.

"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," the authors concluded, adding that this "allows the identification of patients with a high HCV infection risk."

In another study reported in the January 6 edition of BMC Public Health, Axel Schmidt of Checkpoint Zurich and colleagues assessed HCV infection rates among mostly HIV negative MSM recruited at a gay health center and at venues such as dark rooms, saunas, and cruising areas in Zurich.

A total of 840 participants completed anonymous risk factor questionnaires and were tested for HCV. Of these, 19 (2%) were HIV positive. Overall, 7 men tested positive for HCV antibodies (indicating past infection) and 2 were also positive for HCV core antigen and HCV RNA (indicating current active infection). None were aware they had HCV. Among the 821 HIV negative men, HCV seroprevalence was 0.37% -- similar to that of the general population -- and 1 person (0.21%) had active replicating HCV.

Significant predictors of HCV infection included being HIV positive (OR 72.2), having tattoos (OR 10.4), non-injection use cocaine or amphetamines (OR 8.8), and non-Swiss origin (OR 8.5). Among MSM without HIV, having tattoos was the only variable marginally associated with HCV infection (OR 8.3). No significant associations were observed with injection drug use, unprotected anal intercourse, traumatic sexual practices, group sex, or sexually transmitted infections that cause lesions.

"Our findings suggest that in Switzerland, hepatitis C among MSM without diagnosed HIV is not more prevalent than in the general population," the researchers concluded. "We found no evidence of elevated rates of sexual transmission of HCV among MSM without HIV infection. Therefore, we currently see no reason for promoting HCV testing among all MSM in Switzerland."

HCV in Semen

Finally, in a study presented at the recent Conference on Retroviruses and Opportunistic Infections (CROI), Daniel Bradshaw from the Kirby Institute at the University of New South Wales and colleagues looked at HCV viral load in the blood and semen of men who have sex with men. They hypothesized that HCV sexual transmission in this population may be due to high semen HCV RNA levels during acute or recent HCV infection. 

The analysis included 66 HCV positive men, of whom 18 (27%) were HIV positive and had acute or recent HCV infection (less than 12 months; mean 3.5 months), 22 (33%) were HIV positive and had chronic HCV infection, and 26 (39%) were HIV negative and had chronic HCV infection. Among the HIV positive men, nearly 90% were on antiretroviral therapy with undetectable HIV RNA and the median CD4 count was approximately 600 cells/mm3. HCV genotype 1a was most common (58%), followed by 3a (27%) and 1b (8%). None were taking hepatitis C treatment.

Semen HCV RNA was detected in 29 men (44%) at baseline. Men with acute and chronic HCV infection had a similar likelihood of having detectable semen HCV, as did HIV positive and HIV negative men.

The overall median blood plasma HCV RNA level was 6.1 log IU/mL, which again did not differ significantly between men with acute versus chronic HCV or between those who were HIV positive versus negative. When detectable, the median semen HCV RNA level was 2.1 log IU/mL, and HCV RNA levels in semen and blood were correlated. Median blood plasma HCV RNA was significantly higher in men with detectable semen HCV RNA in the HIV positive acute HCV group (6.2 vs 4.6 log IU/mL), but not in the HIV positive chronic HCV group or the HIV negative group.

Among the 35 men who underwent follow-up testing after a median of 18 weeks, 26 (74%) had detectable semen HCV RNA in at least1 sample, including 12 (34%) with 2 HCV positive semen samples. Median blood plasma HCV RNA was significantly higher in men with 2 positive semen samples. The presence of other sexually transmitted infections was not significantly associated with HCV shedding in semen.

"Semen HCV RNA was detected in 43.9% of men at baseline, at median 4.0 log IU/mL less than plasma. In 40.0% of men followed up, shedding was intermittent," the researchers concluded.

"For men with [HIV and acute HCV], detectable semen HCV RNA was more likely with higher plasma HCV RNA, implying a possible relationship between HCV dynamics in plasma and semen in the acute phase," they continued. "If, as previously described, HIV coinfected individuals in early acute HCV have a higher plasma HCV RNA, this could lead to raised semen levels, facilitating sexual transmission."



JW Vanhommerig, IG Stolte, FAE Lambers, et al. Hepatitis C Virus Incidence in the Amsterdam Cohort Study Among Men Who Have Sex With Men; 1984-2011. 49thEuropean Association for the Study of the Liver International Liver Congress (EASL 2014). London, April 9-13, 2014. Abstract O92.

AT Urbanus, TJW Van De Laar, R Geskus, et al. Trends in hepatitis C virus infections among MSM attending a sexually transmitted infection clinic; 1995-2010. AIDS 28(5):781-790. March 13, 2014.

RD Kouyos, A Rauch, J Böni, et al (Swiss HIV Cohort Study). Clustering of HCV coinfections on HIV phylogeny indicates domestic and sexual transmission of HCV. International Journal of Epidemiology. January 22, 2014 (Epub ahead of print).

AJ Schmidt, L Falcato, B Zahno, et al. Prevalence of hepatitis C in a Swiss sample of men who have sex with men: whom to screen for HCV infection? BMC Public Health 14:3. January 6, 2014.

D Bradshaw, F Lamoury, B Catlett, et al. Seminal HCV RNA Level May Mirror Dynamics of Plasma HCV RNA in HIV-Positive Men With Acute HCV. 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014). Boston, March 3-6, 2014. Abstract 676.