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 last month at the 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.
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.
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.
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
“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
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.