Widespread PrEP use is not leading to more hepatitis C transmission among gay and bisexual men

The incidence of hepatitis C infection is now four times lower in gay and bisexual PrEP users than it was before direct-acting antivirals for the treatment of hepatitis C became available without restrictions in higher-income countries, Australian researchers reported this week at the 24th International AIDS Conference in Montreal.

Hepatitis C prevalence rose among gay and bisexual men with HIV during the decade before direct-acting antiviral treatment for the infection became widely available in Europe and North America after 2015. Hepatitis C appeared to spread in sexual networks where unprotected anal intercourse took place predominantly between men living with HIV.

There have been concerns that increased use of PrEP and a reduction in condom use among gay and bisexual men could lead to an increased incidence of hepatitis C in HIV-negative gay and bisexual men, as a result of more condomless sex between men with differing HIV statuses.

Michael Traeger and colleagues at the Burnet Institute and Monash University, Melbourne, carried out a systematic review and meta-analysis to investigate the incidence of hepatitis C during PrEP use in cohorts of gay and bisexual men, as well as the prevalence of hepatitis C antibody and chronic hepatitis C in gay and bisexual men starting PrEP.

The researchers identified 18 studies published between 2015 and 2022 that reported on incidence, conducted in Australia, North America and Europe.

Hepatitis C incidence was higher in studies that began before broad access to direct-acting antivirals than in studies that began follow-up after there was broad access.

Twelve studies that began follow-up prior to broad access reported hepatitis C incidence ranging from zero cases per 100 person-years of follow-up to 2.93 cases per 100 person-years of follow-up, but the confidence intervals in many of these studies were wide. The meta-analysis estimated a pooled incidence of 1.27 cases per 100 person-years prior to broad access.

After broad access – the timing varied from country to country – six studies reported substantially lower incidence, in all cases below the pooled average for the 18 studies in the meta-analysis, with a pooled incidence of 0.81 cases per 100 person-years of follow-up.

The meta-analysis also found a higher prevalence of prior hepatitis C exposure, indicated by hepatitis C antibody, and chronic hepatitis C infection, shown by hepatitis C RNA, prior to broad direct-acting antiviral access. Some people may clear hepatitis C spontaneously after acute infection while treatment may have cured others, but anyone exposed to the virus will retain antibodies, so antibody testing is indicative of historical prevalence.

Before broad access, 1.75% of people starting PrEP had hepatitis C antibodies, compared to 0.63% in the period after broad access was enabled.

Similarly, hepatitis C RNA prevalence was lower in PrEP starters after broad access was enabled. In the earlier period, RNA prevalence was 0.95%, whereas prevalence was 0.24% in the later period.

The study authors say that lower hepatitis C RNA prevalence in the broader-access period is not fully explained by greater enrolment of people with a lower risk of acquiring hepatitis C as time went on. Instead, they say, it is likely that declines in the prevalence of chronic and acute hepatitis C due to treatment prior to wider access to PrEP explain the substantially lower incidence of hepatitis C after broader access to direct-acting antivirals was enabled. Treatment is likely to have reduced transmission in gay and bisexual men’s sexual networks.