An unexpectedly high number of HIV-negative gay and bisexual men taking pre-exposure prophylaxis (PrEP) in Amsterdam were found to have hepatitis C virus (HCV) infection, suggesting HCV is being transmitted sexually between men with and without HIV, according to a presentation at February's Conference on Retroviruses and Opportunistic Infections (CROI 2017) in Seattle.
Starting in the early 2000s, researchers in the UK and elsewhere in Europe have reported 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 US.
Several risk factors have been implicated – including condomless anal sex, fisting, use of sex toys, other sexually transmitted infections (STIs) and non-injection drug use – but these have not been consistent across studies. Experts have traditionally assumed that HCV is transmitted through sexual activities that involve blood, but the virus has also been detected in semen, rectal secretions and faeces.
To date, sexually transmitted HCV has mostly been seen among HIV-positive MSM, with much lower rates (generally around 1% or less) among HIV-negative men, comparable to that of the general population. But cases of apparent sexually acquired HCV have been reported among HIV-negative gay men as well – including in the Kaiser Permanente San Francisco PrEP programme and the UK PROUD and French Ipergay PrEP studies – and there is some evidence these may be increasing.
Elske Hoornenborg and colleagues looked at HCV prevalence among HIV-negative gay and bisexual men at high risk for acquiring HIV who enrolled in the Amsterdam Pre-Exposure Prophylaxis Project (AMPrEP) run by the Amsterdam Public Health Service.
Men seeking PrEP were tested for HCV antibodies (indicating that someone has ever been infected, including those who spontaneously cleared the virus or were successfully treated) and HCV RNA (indicating active viral replication).
Among those who tested positive for HIV RNA, part of the HCV NS5B gene was sequenced and used to construct phylogenetic trees. These show how closely related viruses from different people are and can shed light on transmission networks.
The researchers compared HCV sequences from 375 HIV-negative AMPrEP participants and 182 HIV-positive gay and bi men with acute HCV infection in the Dutch MOSAIC cohort.
They found that 18 of the HIV-negative AMPrEP participants, or 4.8%, tested positive for either HCV antibodies or HCV RNA at baseline. Most men (15, or 83%) had detectable HCV RNA showing active infection, including one without detectable antibodies, suggesting very recent infection.
This 4.8% prevalence among HIV-negative gay and bisexual men seeking PrEP was higher than the prevalence of around 1% previously seen among HIV-negative Dutch MSM who were not taking PrEP, the researchers noted.
HCV genotyping showed that most HIV-negative men (73%) had genotype 1a, which is common in Europe and the US; three men (20%) had genotype 4d, which is predominant in the Middle East and North Africa but also often seen in MSM clusters in Europe; and one man (7%) had genotype 2b.
Of the 15 participants with detectable HCV RNA, 13 (87%) were part of six MSM-specific clusters with related virus, and these all included both HIV-positive and HIV-negative gay men. The three HIV-negative men with HCV genotype 4d and the single man with 2b were in these clusters, while nine of the 11 men with genotype 1a belonged to four separate clusters.
Nearly a quarter of the gay men testing positive for HCV (four out of 18) reported injecting drugs during the three months before starting PrEP – much higher than the 3% (11 out of 357) among HCV-negative participants. The majority, however, did not have injection-related risk.
In addition, men who tested positive for HCV were younger on average than those without HCV (median 33 vs 40 years), had more anal sex partners (median 20 vs 15), and were more like to have been recently diagnosed with chlamydia, gonorrhoea, or syphilis (61 vs 35% in the past six months) and to have engaged in ‘chemsex’, or use of certain recreational drugs during sex (83 vs 40% in the past three months).
“HCV prevalence among HIV-negative MSM who started PrEP was higher than expected (based on the literature),” the researchers concluded. “HIV-negative MSM with HCV infection were infected with HCV strains already circulating among HIV-positive MSM, which suggests overlap between HIV-positive and HIV-negative MSM.”
Based on these findings, they recommended that routine HCV testing should be offered to gay and bisexual men at high risk for HIV, especially those enrolling in PrEP programmes.
Presenting similar data at the recent HIV in Europe (HepHIV2017) meeting in Malta, Maria Prins of the Amsterdam team suggested that diagnosing and treating hepatitis C early in high-risk gay and bisexual men could potentially bring about a rapid reduction in overall HCV incidence in this population.
Another study presented at CROI indicates this may already be happening. Bart Rijnders and colleagues reported that new HCV infections among HIV-positive gay and bisexual men at health centres throughout the Netherlands have dropped by half in just over a year since the country instituted a policy of unrestricted access to direct-acting antivirals for hepatitis C treatment.
Hoornenborg E et al. High prevalence of hepatitis-C virus among HIV negative MSM in Amsterdam PrEP Project. Conference on Retroviruses and Opportunistic Infections (CROI 2017), Seattle, abstract 519, 2017.
Update: Following the conference presentation, this study was published in a peer-reviewed journal:
Hoornenborg E et al. MSM starting preexposure prophylaxis are at risk of hepatitis C virus infection. AIDS, 31: 1603-1610, July 2017.