Epidemic of sexually transmitted hepatitis C in gay men now involves both HIV-positive and HIV-negative men

Incidence of acute hepatitis C virus (HCV) among men who have sex with men (MSM) who use pre-exposure prophylaxis (PrEP) in Lyon increased tenfold between 2016 and 2017, according to research published in Clinical Infectious Diseases. There was also a doubling of incidence among HIV-positive MSM, mainly as a result of reinfection. There were distinct clusters of infections, over half involving both HIV-positive and HIV-negative men. 

“Our cohort study clearly demonstrates that the HCV epidemic has now spread in HIV-negative MSM,” comment the authors. “The incidence of AHI [acute hepatitis C incidence] was particularly high in PrEP-using MSM.” The authors believe that measures to control the HCV epidemic among MSM should include routine and frequent testing for all high-risk individuals. For those diagnosed with acute infection, rapid initiation of HCV therapy with direct-acting antivirals (DAAs) and harm reduction is needed.

There’s now considerable evidence of sexual transmission of HCV among HIV-positive MSM. Outbreaks are now being reported among HIV-negative MSM. Investigators in Lyon wanted to further understand the dynamics of HCV transmission among both HIV-positive and HIV-negative MSM, including incidence, clustering and risk factors. They therefore designed a study involving all cases of acute HCV among MSM documented in the city between 2014 and 2017. HCV samples were genetically analysed to see if infections were clustered and whether there were distinct transmission networks.

During the study period, there were a total of 108 acute HCV infections involving 96 MSM (80 first infections and 28 reinfections). Risk factors for HCV included injecting drug use (33%), snorting drugs (34%), group sex (69%) and fisting (24%).

At least one risk factor was reported by 79% of HIV-positive and 96% of HIV-negative men.

HIV-negative patients were significantly younger than HIV-positive individuals (median age, 37 vs 47 years, p = 0.02) and were more likely to report drug use (96% vs 40%, p < 0.001) and fisting (50% vs 15%, p = 0.02). Two-thirds of HIV-negative men were receiving PrEP at the time of HCV diagnosis. An additional 12% of HCV infections among HIV-negative MSM were picked up at PrEP screening.

The number of acute HCV cases diagnosed per year doubled from 20 cases in 2014 to 40 cases in 2017. By 2017, HIV-negative men represented 45% of acute diagnoses.

Incidence in HIV-positive MSM more than doubled, from 1.1 cases per 100 person-years in 2014 to 2.4 cases per 100 person years in 2017. However, this increase was only significant for reinfections, increasing from 4.8 per 100 person-years in 2014 to 11.8 cases per 100 person-years in 2017. The rate of first infections remained relatively stable, increasing from 1.1 to 1.5 cases per 100 person-years over the same period. In contrast, incidence of first infections among PrEP users increased tenfold between 2016 and 2017, from 0.3 cases per 100 person-years to 3.0 cases per 100 person-years in 2017.

Spontaneous cure was observed in 8% of cases. HCV therapy using DAAs was initiated by 94 people, an average of five months after the estimated date of infection. The overall sustained virological response rate was 96%.

The most frequent HCV genotypes were 1a (55%), 4d (31%) and 3a (7%). Phylogenetic analysis showed that 96% of acute infections belonged to a cluster. Eight distinct clusters – involving between three and 27 sequences – were identified. All the clusters involved an individual with HIV, with five also involving an HIV-negative man. Six clusters involved an individual who was infected with HCV before 2014, though acute infections were now driving the epidemic.

Analysis of the five largest clusters showed that four were strongly associated with drug use (45 to 85% of men), with fisting (50%) an additional risk factor in one of them. Seventeen infections between January 2016 and July 2017 involved closely related virus. These infections were in individuals sharing multiple risk factors. One cluster of patients diagnosed between June and August 2017 involved six patients, all reporting nasal drug use and with a recent bacterial STI, possibly suggesting HCV transmission between these individuals at a single event.

“This study reveals the changing epidemiology of AHI in MSM in Lyon, France, in recent years, spreading from HIV-infected patients to HIV-negative patients through sharing of high risk activities such as chemsex and traumatic sexual practices,” write the authors. “All clusters started with an HIV-infected MSM, suggesting that the epidemic started in this population and later spread to HIV-negative MSM.”

The authors believe their findings have important implications for the control of sexually transmitted HCV in MSM. They urge that all MSM with high-risk behaviour should be routinely and regularly screened for HCV. DAA therapy and harm reduction should be provided early following diagnosis of acute HCV, thus limiting the risk of onward transmission.

A further analysis of the same group of patients was presented to the Conference on Retroviruses and Opportunistic Infections (CROI 2019). This showed the importance of rapid diagnosis, treatment and harm reduction. Each MSM with acute HCV infection was estimated to pass on the infection to 2.35 other MSM within five months.