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.
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.
Hagan and 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searched the English-language medical literature, including the PubMed, EMBASE and BIOSIS databases, as well as unpublished reports from major HIV and hepatitis conferences, for relevant studies conducted between January 1990 and February 2015.
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. Seroconversion 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 months. Reinfection following treatment was determined by the presence of a different 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 person-years.
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 100 person-years).
However, the analysis showed that the pooled HCV reinfection rate for MSM living with HIV following successful treatment was 20 times higher than the rate of initial seroconversion, and two-year cumulative incidence after sustained response in two studies was 25-33%. In one study five gay men with HIV were reinfected more than once after treatment, and multiple reinfections have also been seen among men who experienced spontaneous HCV clearance.
"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."
Hagan H et al. Incidence of sexually transmitted hepatitis C virus infection in HIV-positive MSM. AIDS, 7 August 2015 (online ahead of print).