Fewer than one in eight gay or bisexual men with HIV
spontaneously cleared a recent infection with hepatitis C, a large European
study of recent hepatitis C infections has found. The study investigators say
that if hepatitis C virus levels don’t decline within a month of diagnosis in
gay or bisexual men at high risk of recent acquisition of hepatitis C,
direct-acting antiviral treatment should be offered – and in some cases,
doctors should not wait, but should offer treatment upon diagnosis.
The findings, published in the journal Clinical
Infectious Diseases, come from the PROBE-C study, an observational cohort
study of recent hepatitis infections in people with HIV in western Europe. The
study was designed to evaluate the rate of spontaneous clearance of hepatitis C
in people with HIV and responses to treatment for hepatitis C initiated during
Spontaneous clearance of hepatitis C has been observed in
between 25 and 50% of people without HIV and is more common in women. In
people with HIV, cohort studies have reported spontaneous clearance rates
between 5 and 20%.
Determining how often spontaneous clearance happens and when
it is no longer likely to happen could enable doctors to decide when to offer
direct-acting antiviral therapy to people with recent infection. Treating acute
infection could limit the sexual transmission of hepatitis C among gay and
bisexual men with HIV, whereas waiting for spontaneous clearance – which may be
a low-probability event – could permit further hepatitis C transmission.
The study recruited people with HIV with a positive
hepatitis C RNA test within the past year and a negative hepatitis C antibody
or RNA test 12 months prior to the positive hepatitis C RNA test.
People were also eligible to join the study if they had a
negative hepatitis C antibody test and a history of normal liver enzymes
followed by a persistent increase in ALT and a positive HCV antibody result.
The study enrolled 464 participants between 2007 and 2017;
all but seven were men. Almost all participants were exposed to hepatitis C
through sex between men. Sharing of injecting equipment was a risk factor for
hepatitis C transmission in only 0.7% of those recruited to the study. Fifty-one
participants had been reinfected with hepatitis C.
Ninety-one per cent were taking antiretroviral treatment, 90%
had a suppressed viral load and the median CD4 count of participants was 574.
Spontaneous clearance occurred in 55 participants (12%), a
median after 13 weeks after the first positive HCV-RNA test. The absence of an
HCV RNA decline of at least 2log, four weeks after diagnosis, was associated
with a very high probability of persistent, or chronic, infection.
The study investigators say that this finding leaves no
doubt as to when treatment should start in people who have been diagnosed with
recent infection: as reflected in European AIDS Clinical Society guidelines,
direct-acting antiviral treatment should start four weeks after diagnosis if
HCV viral load has not fallen by 2log.
Seventy-nine per cent of participants subsequently initiated
hepatitis C treatment in the 144-week follow-up period. Participants started
pegylated interferon treatment a median of 14 weeks after diagnosis, compared
to 44 weeks after diagnosis for people initiating direct-acting antiviral treatment.
The delay in initiating direct-acting antiviral treatment was due to
reimbursement and licensing restrictions on the use of direct-acting antivirals
during acute infection. Only 14% of people diagnosed after the introduction of
direct-acting antivirals in 2017 were able to initiate treatment within 24
weeks, compared to 75% in 2007.
The cure rate in people receiving direct-acting antivirals
was 93%; in people receiving pegylated interferon, it was 73%.
The study investigators say that their findings reinforce
recommendations that direct-acting antiviral treatment should start as soon as
recent hepatitis C infection is diagnosed, to limit onward transmission.
Although the long-term benefit of early hepatitis C treatment is unclear, the
investigators say that the consequence of not treating is clear in people with
HIV: faster progression of liver progression and earlier development of liver
cirrhosis and other complications, compared to people without HIV.