Hepatitis C epidemic in US gay men is decades old

Hepatitis C virus (HCV) transmissions have been occurring in gay men since at least the early years of the HIV epidemic, investigators from the US report in the online edition of Clinical Infectious Diseases. The vast majority of infections involved men living with HIV. Unprotected receptive anal sex and recent infection with syphilis were both risk factors for incident infections, and for men living with HIV, there was a significant relationship between a lower CD4 cell count and acquiring HCV.

“Our data demonstrate that HCV acquisition has been ongoing in the MSM [men who have sex with men] population in the United States since the early HIV epidemic,” write the authors. “Although HCV infections occurred in both HIV-infected and -uninfected MSM, the rates in HIV-infected men are significantly higher. Furthermore among HIV-infected MSM, this is the first study to report a significantly higher HCV IR [incident rate] in men with lower CD4 T-cell counts.”

HCV is a bloodborne virus and most transmissions can be attributed to contact with infected blood. The risk of sexual transmission of HCV for heterosexual people appears to be very small. However, there are ongoing outbreaks of sexually transmitted HCV among HIV-positive gay men in a number of countries.

Investigators from the Multicenter AIDS Cohort Study (MACS) wanted to see if the HCV epidemic in gay and other MSM was in fact a relatively new phenomenon.

They therefore designed a study involving 5310 gay and other MSM who were followed between 1984 and 2011. All were HCV uninfected at baseline, and the investigators tested stored plasma samples to determine incidence of HCV. The researchers also conducted a series of analyses to see if they could identify specific risk factors for infection with the virus.

Most of the men (4384) were recruited in the 1980s or early 1990s, with the remainder entering the study between 2001-03. Overall, unprotected receptive anal sex was reported by 36% of men, 3% had had a blood transfusion, 5% reported a history of injecting drug use and 5% had chronic hepatitis B virus (HBV) infection. Just over a third of men (38%) had HIV, but baseline prevalence differed between men recruited in the 1980s/90s and those recruited in the later period (36 vs 52%).

Study participants were followed for a median of seven years and provided a total of 55,343 person-years for analysis. During this time there were 115 incident HCV infections, a rate of 2.08 per 1000 person-years.

Incidence was over eightfold higher in HIV-positive men than HIV-negative individuals (4.22 per 1000 person years vs 0.50 per 1000 person years, p < 0.001).

The investigators found evidence of HCV transmissions from the very beginning of follow-up. There were 41 new infections among HIV-positive men between 1984 and 1989, with eight incident infections among HIV-negative men during the same period. Incidence remained significantly higher among HIV-positive men for the duration of the study, but a total of eight further infections were detected in the HIV-negative recruits between 1990 and 2011.

Interestingly, incidence among HIV-positive men in their first four years of follow-up was similar for those recruited in the 1980s/90s and the men recruited between 2001-03 (5.62 per 1000 person-years vs 6.74 per 1000 person-years).

Between 2005-11, incidence among HIV-positive men was 2.57 per 1000 person-years for those recruited in the 1980s and 1990s and 5.16 per 1000 person-years for those entering the study between 2001-03. The corresponding rates for HIV-negative men were 0.53 per 1000 person-years and 2.33 per 1000 person-years respectively.

The investigators’ first analysis showed that a number of risk factors were associated with acquiring HCV infection. The most important were current injecting drug use (IRR = 16.22; 95% CI, 8.85-29.72, p < 0.001), heavy alcohol consumption (IRR = 16.22; 95% CI, 8.85-29.72, p < 0.001), recent infection with syphilis (IRR = 8.45; 95% CI, 3.45-20.70, P < 0.001), infection with HIV (IRR = 8.40; 95 % CI, 4.96-14.25, p < 0.001), unprotected receptive anal sex with multiple partners (IRR = 7.44; 95% CI, 4.24-13.06, p < 0.001) and receipt of blood products (p = 0.001)

The authors then controlled for potential confounders and excluded men who reported injecting drug use or blood transfusions. This analysis showed that infection with HIV (IRR = 7.56; 95% CI, 5.56-10.44, p < 0.001), infection with HBV (IRR = 2.14; 95% CI, 1.53-2.99, p < 0.001) and unprotected receptive anal sex with multiple partners (IRR = 4.02; 95% CI, 1.60-10.13, p = 0.003) were all associated with an increased risk of incident HCV infection.

“Other studies have shown that traumatic sexual behaviors are associated with HCV transmission amongst MSM,” the investigators note. “We did not record these practices throughout follow-up so could not determine [if] they increased HCV transmission.”

For men with HIV, each 100 cell/mm³ increase in CD4 cell count was associated with a significant 7% (p = 0.002) reduction in the risk of infection with HCV up to a CD4 cell count of 500 cells/mm³.

“It seems plausible that HIV-related immunosuppression could reduce the infection threshold needed for a productive systemic infection,” suggest the authors. 

They conclude that the HCV epidemic in “both HIV-infected and -uninfected MSM has been going on for decades…these findings underscore the need for active prevention, counseling, and diagnosis of HCV in all MSM.”