Two HIV-negative gay men receiving HIV pre-exposure prophylaxis (PrEP) through Kaiser Permanente in San Francisco were newly infected with hepatitis C virus (HCV), with sex being their only apparent risk factor, Kaiser clinicians reported in the February 18 issue of Clinical Infectious Diseases.
HCV was traditionally thought to be rarely transmitted through sex, but this was based on studies of monogamous heterosexual couples. Starting in the early 2000s clinicians began reporting clusters of apparently sexually transmitted acute HCV infection among HIV-positive men who have sex with men in cities in the UK, Europe, Australia and the US. Most studies to date have found that HCV sexual transmission among HIV-negative gay and bisexual men remains uncommon, but some experts think it is increasing.
In their Clinical Infectious Diseases letter, Jonathan Volk, Brad Hare and colleagues from Kaiser Permanente San Francisco - thought to be the largest PrEP provider in the US - reported that two gay men were newly infected with HCV out of 485 people who started Truvada (tenofovir/emtricitabine) PrEP between February 2011 and December 2014. With approximately 300 person-years of follow-up data, the incidence rate was 0.7 cases per 100 person-years, falling within the range of previous studies of acute hepatitis C among HIV-negative men.
Hare reported this past December that no new HIV infections have occurred among more than 500 Kaiser San Francisco members who started PrEP. But other sexually transmitted diseases (STDs) have been common, including syphilis, gonorrhoea and chlamydia, along with the two unusual acute HCV infections (in addition to two pre-existing but previously undiagnosed cases).
As described in the published report, both people with new HCV infection were gay men who reported multiple sex partners and had other STDs. Both had new gonorrhoea, syphilis, and rectal chlamydia. One man reported receptive anal sex with a partner who had a penis piercing and was a bottom during group sex. The men reported no injection drug use, no occupational exposure and had no tattoos.
"I'm comfortable saying both are sexual transmission," Hare told HIVandHepatitis.com/Aidsmap.
Acute HCV infection among gay men has been associated in various studies with anal sex, fisting, using sex toys, having multiple sex partners, sex in public venues, use of non-injected recreational drugs, sex while using drugs and having other STDs.
It remains unclear whether HCV is primarily transmitted through blood or semen during sex. Some studies have detected HCV in semen from about 40% of men with hepatitis C. Some research has shown that HIV-positive men are more likely to have HCV in their semen than HIV-negative men, and that acute HCV infection is associated with higher HCV semen viral load than chronic infection, but findings have not been consistent across studies.
Both men with acute HCV infection in the Kaiser programme were diagnosed based on elevations in their alanine aminotransferase (ALT) liver enzyme levels. While acute hepatitis C is often asymptomatic, both men reported symptoms including fatigue, nausea, aching joints and flank pain. One man was found to have HCV genotype 1 (the most common type in the US) while the other had genotype 4 (most common in the Middle East, but seen in some sexual transmission clusters in Europe).
Kaiser's PrEP program does HIV and liver function testing every three months and HCV testing annually. ALT is a marker of liver inflammation; if it rises with no other known cause, such as drug toxicity, it may indicate recent infection with hepatitis A, B or C and should prompt follow-up testing for these viruses. Liver function tests are simple and inexpensive and can pick up acute HCV infection before the body produces enough antibodies to show up on an HCV antibody test.
In December Hare also presented results from a survey of approximately 90 people in the Kaiser programme, which found that 45% of respondents said they used condoms less since starting PrEP, while 5% said they used them more and the rest reported no change.
PrEP clinical trials generally have not seen evidence of so-called 'risk compensation' -- engaging in more risky behaviour or reducing use of other prevention methods. But anecdotal reports in the gay community suggest that many men feel that dispensing with condoms is a major benefit of PrEP.
Several experts think the rise of serosorting in the late 1990s, after the advent of effective antiretroviral therapy, contributed to the increase in sexually transmitted HCV among HIV-positive gay men. Some have suggested PrEP may have a similar effect among HIV-negative men.
Today hepatitis C can be effectively treated with newly approved direct-acting antivirals. These oral regimens usually last 12 weeks, are well-tolerated and cure more than 90% of treated patients. But they are very expensive and insurers and public payers are trying to limit their use. Importantly, having HCV does not confer immunity and people can become reinfected.
In light of these new HCV infections, the authors recommend on-going HCV monitoring for HIV-negative gay and bisexual men receiving PrEP. U.S. Center for Disease Control and Prevention (CDC) guidelines currently call for HCV testing before starting PrEP, but do not mention regular monitoring thereafter.
"It's important for HIV negative men thinking about PrEP to be counselled about HCV," Hare told Aidsmap/HIVandHepatitis.com. "If they're maybe going to decrease their condom use, they should know HCV is a risk. We talk about other STDs, but HCV is the big one to be concerned about."
Volk J et al. Incident hepatitis C virus infections among users of HIV preexposure prophylaxis in a clinical practice setting. Clinical Infectious Diseases. February 18, 2015 (epub ahead of print).