Sexual transmission of hepatitis C virus (HCV)
is occurring among HIV-positive men who have sex with men (MSM), associated
with receptive anal sex and non-injection drug use, and a small subset of men
may be prone to recurrent infection after being cured of hepatitis C, according
to a meta-analysis reported in the August 7 online
edition of AIDS.
"[I]f one thousand HIV-positive MSM
were followed for one year each, approximately five would acquire HCV," said
lead researcher Holly Hagan from the Center for Drug Use
and HIV Research at New York University. "This is far lower than the rates among people who inject
drugs. However, when we pooled the data across studies and looked at incidence
in relation to calendar time, we saw an increase."
Starting in the early 2000s researchers in the UK
and elsewhere in Europe began reporting clusters of apparently sexually transmitted
acute HCV infection among gay and bisexual men living with HIV in major cities;
similar outbreaks followed in the US and Australia.
Improvement in a tumour. Also, a mathematical model that allows us to measure the degree to which one of more factors influence an outcome.
Various risk factors have been implicated –
including condomless anal sex, fisting, group sex, other sexually transmitted
infections (STIs) and non-injection recreational drug use – but these have not
been consistent across studies. Some research has found that people who
already have HIV when they contract HCV may experience unusually rapid liver disease progression, but
here too data are conflicting.
her colleagues conducted a systematic review and meta-analysis
to better understand sexually transmitted HCV among gay and bi men living with HIV.
The researchers searched the
English-language medical literature, including the PubMed, EMBASE and
BIOSIS databases, as well as unpublished reports from major HIV and hepatitis
conferences, for relevant studies conducted between January 1990 and February
They focused on studies that looked
at HCV seroconversion or reinfection after successful hepatitis C
treatment in MSM living with HIV who did not inject drugs.
or acute HCV infection was determined according to European AIDS
Treatment Network (NEAT) criteria: a positive HCV RNA test
following a negative HCV RNA or HCV antibody test in the previous 12
Reinfection following treatment was determined by the presence of a
HCV genotype or clade, to distinguish it from relapse.
Out of 779 potentially relevant
abstracts, the researchers fully assessed 173 reports and identified 25 to be
included in the meta-analysis – 21 that looked at initial HCV seroconversion
and four on post-treatment reinfection. Half the studies were from Europe, four from the
US, three from Asia and two from Australia – all looking at men in urban
settings in high-income countries.
Of these, 17 reports included HCV
incidence density numbers that could be used to calculate pooled rates; there
were two reports each from the Amsterdam Cohort Study and Swiss HIV Cohort,
both of which were included only once in the pooled calculation. Of the four
reinfection studies, two included incidence density. Only four of the 21
selected seroconversion studies reported risk factors in an adjusted analysis
that included only MSM who were not injection drug users.
Altogether, the pooled estimate
included data from more than 13,000 men in 15 unique studies followed for more
than 93,000 person-years between 1984 and 2012, yielding 497 total cases of HCV seroconversion.
HCV seroconversion or incidence
rates in the included studies ranged from 0.00 to 1.40 per 100
person-years. The overall pooled HCV incidence rate was 0.53 per 100
Calendar year was a significant
factor associated with HCV seroconversion, with estimated incidence rates
rising from 0.42 per 100 person-years in 1991 to 1.09 in 2010 and 1.34 in 2012.
The pooled HCV reinfection rate was
11.4 per 100 person-years, based on two studies which showed rates of 9.6 and 15.2
per 100 person-years, respectively, in London and Amsterdam.
Among men who experienced HCV
seroconversion, new infections were primarily associated with condomless
receptive anal sex, 'traumatic' sex that could cause rectal mucosal damage or
bleeding, fisting, sex while using methamphetamine and using inhaled drugs.
"The data show an upward trend beginning in about 1995," the study
authors noted in their discussion. "If the trend identified in the meta-regression
has continued to the present, current incidence may be as high as 1.92 [per]
100 person-years, but the predictions also show increasing uncertainty over the
past several years."
These HCV incidence rates, they explained,
"are still relatively low compared with people who inject drugs",
and in fact the highest rates of HCV infection among gay men living with HIV do
not reach the lower bound of the range for injection drug users (5 to 60 per
However, the analysis showed that the pooled HCV
reinfection rate for MSM living with HIV following successful treatment
times higher than the rate of initial seroconversion, and two-year
incidence after sustained response in two studies was 25-33%. In one
study five gay men with HIV were reinfected more than once after
multiple reinfections have also been seen among men who experienced
"These data indicate that there exists a
subgroup of HIV-positive MSM with recurring sexual exposure to HCV in whom the
rates may begin to approach the risk of HCV infection among people who inject
drugs," the researchers concluded. "A large proportion of infections
in the HCV seroconverters were attributable to mucosally traumatic sex and sex
while high on methamphetamine."
"Recommendations for management of acute
HCV in HIV-positive MSM centre on detection through screening for elevated
liver enzymes every 3-6 months and providing either early or delayed
treatment," they wrote. "However, the high rates of reinfection and
the cost of treatment with the new direct-acting antivirals may impact on the
feasibility of this approach to HCV control among HIV-positive MSM."
"The multifactorial nature of sexually
transmitted HCV in HIV-positive MSM will require a combination approach
addressing individual sexual and drug use behaviour in the context of a
changing epidemiology," they concluded. "A fuller understanding of
the causal pathways is needed to identify effective strategies, and lessons
learned about HIV prevention in MSM engaging in sexual risk behaviour are a
useful starting point."