cases of hepatitis C virus (HCV) infection among Canadian gay and
bisexual men taking pre-exposure prophylaxis (PrEP) were uncommon
compared with rates previously reported in Europe, according to research
presented this week at the AASLD Liver Meeting in Boston.
"This low incidence is reassuring since studies have shown that risk
behaviour associated with sexually transmitted infections has gone up,"
senior investigator Dr Jordan Feld of the Toronto Centre for Liver
Disease and the University of Toronto said at a media briefing. Based on
these findings, the optimal frequency of HCV testing for people on PrEP
Starting in the early 2000s, researchers in Europe began reporting
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.
"HCV infection has emerged as an STI among HIV-positive
men who have sex with men over the past decade," lead researcher Dr
Sahar Tabatabavakili, also of the Toronto Centre for Liver Disease, said
in an AASLD press releases. "Generally, HIV-positive MSM are
disproportionally affected by HCV compared with HIV-negative MSM, mainly
due to the fact that HIV itself might facilitate sexual transmission of
HCV in addition to different sexual activities and networks of these
Several risk factors have been implicated, including condomless anal
sex, fisting, use of sex toys, having other sexually transmitted
infections (STIs), and using drugs during sex. 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.
Sexually transmitted HCV was initially mostly seen among HIV-positive
gay and bi men. But this has increasingly been reported among
HIV-negative men as well, including participants in the PROUD and Ipergay PrEP studies and the Kaiser Permanente San Francisco PrEP programme.
In 2017, researchers reported an unexpectedly high HCV prevalence rate (total infections) of 4.8% among HIV-negative gay and bi men taking PrEP in Amsterdam. The following year, they reported an HCV incidence rate (new infections) of about 1% in this group – similar to rates for HIV-positive men. A recent study found that HIV-negative men accounted for 45% of new HCV diagnoses among MSM in Lyon, France.
European AIDS Clinical Society and US Centers for Disease Control and
Prevention guidelines recommend that people should be tested for HCV,
as well as bacterial STIs, before they start PrEP. However, they do
not include HCV testing as part of the monitoring that PrEP users are
advised to undergo every three months. AASLD HCV guidelines recommend
HCV testing at least annually at follow-up PrEP visits, with more
frequent testing warranted depending on sexual activity or drug use.
With this as background, Tabatabavakili and colleagues looked at HCV
incidence among PrEP users at the University Health Network HIV
Prevention Clinic. Feld presented the findings after Tabatabavakili, who
is Iranian, was denied a US visa to attend the conference.
This retrospective analysis included all HIV-negative
individuals evaluated for PrEP between October 2014 and September 2019.
Of the 344 participants, 86% were men who have sex with men, three-quarters were white and the median age was 35. A quarter reported ever
injecting drugs – higher than typical rates in studies of gay and bi
Participants were tested for HCV antibodies at baseline and then
every three to six months or any time they had elevated ALT liver
enzymes – a sign of liver inflammation. They also received the
recommended tests for chlamydia, gonorrhoea and syphilis every three
At baseline, five people (1.8%) were found to be positive for HCV
antibodies (showing that they had ever been infected) and HCV RNA
(indicating current infection). This is more than double the rate of
about 0.7% in the Canadian adult population as a whole.
Three of these people were previously aware that they had
hepatitis C, while two were diagnosed for the first time at PrEP
screening. None of them started PrEP and the two newly diagnosed
individuals were referred for treatment but lost to follow-up.
Ultimately, 199 people started Truvada (tenofovir disoproxil
fumarate/emtricitabine) for PrEP. They were required to visit the clinic
every three months to renew their prescription and receive HIV, STI,
HCV and liver enzyme tests.
The incidence of STIs was high, at 49.2 cases of chlamydia, 36.3
cases of gonorrhoea and 5.2 cases of syphilis per 100 person-years of
follow-up. No one was newly diagnosed with HIV during follow-up.
Acute HCV infections were much less common than bacterial STIs. Just
two people – both men who have sex with men – were newly diagnosed,
for an incidence rate of 0.7 per 100 person-years.
One of the men, age 66, was diagnosed with HCV after being on PrEP
for 18.5 months. He reported no history of injection drug use, had
multiple sex partners – one of whom was known to be HCV positive – and
had multiple STIs. The second man, age 24, acquired HCV after being on
PrEP for 14 months. He reported occasional recreational drug use but no
drug injection. He also had multiple sex partners, reported condomless
anal sex and sex work, and had recurrent STIs.
Neither of the men reported any symptoms of hepatitis C and both had
normal ALT levels. Both were treated with direct-acting antivirals and
The researchers noted that the rate of pre-existing HCV among people
starting PrEP in this study was at the low end of the range of
previously reported rates (1.8% to 4.8%).
The rate of new HCV infections was in line with those previously
reported in North America, but lower than those reported in Europe,
which ranged up to 2.9 per 100 person-years in one Belgian study. This
may be due to different patterns of disease transmission, they
suggested. For example, Feld said, drug use associated with sex (so
called chemsex or party'n'play) may be more common in Europe. However,
given that only two people acquired HCV, the researchers were unable to
assess risk factors.
Based on these findings, the study authors concluded that baseline
HCV testing for those starting PrEP "is clearly required". They also
recommended repeat testing because people with newly acquired HCV may
not have symptoms or abnormal ALT levels.
"The low incidence of HCV infections despite very high rates of other
STIs suggests that sexual transmission of HCV is uncommon in
HIV-negative, MSM PrEP users," they concluded. "Cost effectiveness
analyses will be required to determine the optimal frequency of serial
HCV testing and whether risk-based or universal testing is the preferred
strategy in PrEP clinics."
At the press conference, Feld was asked whether preventive therapy
for HCV might be warranted for people at high risk. Current
direct-acting antivirals are highly effective but costly, and
HCV-related liver disease typically does not progress very rapidly. Feld
questioned whether it would be worthwhile to put everyone on HCV
prophylaxis when it is so easy to cure.