SUMMARY: Sexual transmission of hepatitis C virus (HCV) among HIV positive men who have sex with men has now been recognized for a decade, occurring in cities in Europe, North America, and Australia. Since acute HCV outbreaks occur almost exclusively among men with HIV, being HIV positive probably plays a critical role, according to the authors of a review article in the July 31, 2010 issue of AIDS.
By Liz Highleyman
Thijs van de Laar from the Amsterdam Public Health Service and colleagues presented an overview of acute HCV infection among gay/bisexual men with HIV, including epidemiology, risk factors, natural history, disease progression, and challenges of management. The review was based on published studies identified through a MEDLINE search and relevant conference abstracts.
HCV is usually transmitted through direct blood contact, for example, via shared needles for injection drug use (IDU) or blood transfusions before donated blood was screened. Due to common transmission routes, an estimated 4-5 million people -- or approximately one-third of people with HIV -- are HIV/HCV coinfected.
Sexual transmission of HCV was traditionally thought to be uncommon (less than 1%) based on studies of monogamous heterosexual couples. Early cross-sectional studies found a relatively high HCV prevalence rate among men who have sex with men (MSM), but these often did not take into account injection drug use.
Since 2000, however, several outbreaks of acute hepatitis C among HIV positive gay and bisexual men who denied injection drug use have been reported, first in the U.K., then in other large cities in France, Germany, and the Netherlands, followed by Australia, the U.S., and Canada.
ACUTE HEPATITIS C
"Given the burden of liver disease, in particular HCV, on the morbidity and mortality in HIV patients in the era of combination antiretroviral therapy, the rapid and significant rise in the incidence of HCV in the HIV-infected MSM population in high-income countries is alarming," the review authors wrote. "This relates to a significant change in the epidemiology of HCV that has occurred, with HCV emerging as a sexually transmitted infection within this population."
In the Netherlands, for example, a biannual survey among sexually transmitted infection (STI) clinic attendees showed an increase in HCV prevalence among HIV positive MSM from 1%-4% before 2000 to 15% in 2007 and 21% in 2008. HCV prevalence among HIV negative gay/bisexual men, however, remains comparable to that of the general population.
Most cases of acute hepatitis C among MSM in Europe involve hard-to-treat HCV genotypes 1a and 4d, the latter of which is otherwise uncommon in Europe and the U.S. Genetic sequencing has revealed closely related virus strains coinciding with sexual networks.
Evolutionary analysis "suggests multiple independent introductions of HCV into the MSM community, some as early as the 1980s," the authors surmised. "Most likely, these strains were introduced from the IDU population." They noted that the recent increase in HCV sexual transmission coincides with a rise in sexual risk behavior and increased STI rates in the era of effective combination ART, some of which is due to serosorting, or HIV positive men have unprotected sex with other positive men.
Research to date indicates that HCV transmission is associated with a variety of sexual practices -- including fisting, unprotected anal intercourse, use of shared sex toys, group sex, and sex while on drugs -- though specific activities vary from study to study. Other risk factors include non-injection drug use and presence of other sexually transmitted diseases.
These studies show that "most MSM with HCV report a combination of various, potentially high-risk, sexual and drug practices," the authors wrote. "The interaction between sex and drugs is complex, and many of these factors are highly correlated and difficult to disentangle."
"Given this occurs almost exclusively in HIV-infected MSM, HIV probably has a critical role mediated either through behavioral and/or biological factors," they stated. "It is not yet known whether lower CD4 cell count increases the risk of acquiring HCV, but the fact that many MSM with acute HCV have relatively preserved CD4 cell counts suggests this may not be a critical factor."
Disease Progression and Treatment
Turning to hepatitis C disease progression in this population, they wrote, "The natural history of HCV is determined by host-viral interactions, which are perturbed in HIV coinfection, resulting in accelerated liver fibrosis, higher HCV loads, and poorer responses to interferon-based therapy when compared with HCV monoinfection."
While about 25% of HIV negative individuals spontaneously clear HCV without treatment, this is less likely among people with HIV -- as low as 5% in one study -- perhaps due to reduced T-cell responses. HIV/HCV coinfection is associated with more rapid liver fibrosis. Some studies indicate that progression is especially fast among people who already have HIV at the time of HCV infection, but other data are conflicting.
Hepatitis C treatment using pegylated interferon (with or without ribavirin) is quite successful during acute HCV infection. Because they receive regular liver function tests to monitor drug toxicity, people with HIV are more likely to have HCV infection diagnosed during the acute stage. Acute hepatitis C cure rates among HIV positive people are around 60%-80% in most studies.
Optimal timing and duration of therapy for acute HCV infection is not well defined, but most experts recommend waiting 12 weeks to see if spontaneous clearance will occur. Most favor combination therapy over pegylated interferon monotherapy and a treatment duration of 24 weeks for coinfected patients.
"Targeted prevention such as raising awareness, regular screening and treatment of acute and chronic infections are needed to stop the further spread among MSM," the review authors concluded. "It is clear that a message of 'safe sex' through condom use during anal intercourse could be provided, but given the practice of negotiated unprotected sex among HIV-infected MSM might not be accepted. In addition, it may not cover practices that increase risk of blood-to-blood contact (e.g. fisting). Furthermore, MSM population needs to be informed that reinfection is an ongoing risk, given the recent reports of HCV reinfection following successful treatment and documented clearance of HCV."
Cluster of Infectious Diseases, Public Health Service, Amsterdam, Netherlands; Viral Hepatitis Clinical Research Program, National Centre for HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia; Department of Internal Medicine, Centre for Infection and Immunity Amsterdam, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia.
TJ van de Laar, GV Matthews, M Prins, and M Danta. Acute hepatitis C in HIV-infected men who have sex with men: an emerging sexually transmitted infection. AIDS 24(12): 1799-1812 (Abstract). July 31, 2010.