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Starting in the early 2000s researchers in the U.K. and elsewhere in Europe began reporting clusters of apparently sexually transmitted acute HCV infection among HIV-positive gay and bisexual men in major cities; similar outbreaks followed in the U.S. 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 are already HIV-positive when they contract HCV may experienceunusually 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 HIV-positive gay men.

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searched the English-language medical literature, including the PubMed, EMBASE, and BIOSIS databases, as well as unpublished reports from major HIV and hepatitis conference, for relevant studies conducted between January 1990 and February 2015.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 HIV-positive men who have sex with men 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 4 on post-treatment reinfection. Half the studies were from Europe, 4 from the U.S.. 3 from Asia, and 2 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 2 reports each from the Amsterdam Cohort Study and Swiss HIV Cohort, both of which were included only once in the pooled calculation. Of the 4 reinfection studies, 2 included incidence density. Only 4 of the 21 selected seroconversion studies reported risk factors in an adjusted analysis that included only MSM who were not injection drug users.

Results

• 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 was0.53 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 2 studies (15.2 in Amsterdam and 9.6 in London) -- 20 times more frequent than initial HCV seroconversion.
• 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 HIV-positive gay men 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 HIV-positive MSM following successful treatment was 20 times higher than the rate of initial seroconversion, and 2-year cumulative incidence after sustained response in 2 studies was 25%-33%. In one study 5 HIV-positive gay men 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."

"The observed increase in HCV incidence parallels a number of other trends in MSM communities, including an increased use of social media geosocial sexual networking applications and its association with STIs, the increase in 'seroadaptive' sexual behavior that includes unprotected sex between men with the same HIV status, and rising rates of STIs and use of 'chemsex' drugs, including by injection," they continued.

"Recommendations for management of acute HCV in HIV-positive MSM center 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 behavior 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 behavior are a useful starting point."

SEE ALSO: Hepatitis C: A Risk for Gay Men (ACRIA)

9/16/15

Reference

H Hagan, AE Jordan, J Neurer, and C Cleland. Incidence of sexually transmitted hepatitis C virus infection in HIV-positive MSM. AIDS. August 7, 2015 (online ahead of print).

Other Source

New York University. NYU Researchers Observe Upward Trend in Hepatitis C Infection Rates Among HIV+ Men Who Have Sex with Men. Press release. September 9, 2015.