Outbreaks of sexually transmitted hepatitis C infection have been reported among HIV-positive gay men. Early diagnosis and treatment can prevent serious liver disease, but too few doctors notice the warning signs.
BY Tracy Swan
A new epidemic of hepatitis C virus (HCV) infection is on the rise. In the last few years, outbreaks of HCV have been reported among HIV-positive gay men in the United Kingdom, France, the Netherlands, Australia, Germany, and the United States. Many of these cases involve sexual transmission and are associated with group sex and recreational use of noninjection drugs such as ecstasy and cocaine. There have been no reports of an HCV epidemic among HIV-positive women.
When HCV infection is detected and treated early, during the acute phase (within six months of infection), the likelihood of successfully curing the infection is greater than when treatment is begun later. However, acute HCV infection often goes undiagnosed because there are usually no symptoms; there is no specific test to differentiate acute from chronic HCV. The rising number of acute HCV infections in HIV-positive men calls for increased vigilance among doctors and better efforts to provide information to gay men, who are most at risk.
Response to HCV Treatment by HIV Status and in Acute versus Chronic HCV
|Source||Population||Regimen & Duration||SVR||Comments|
|Fried et al.; NEJM 2002||HIV-negative, chronic HC V; N = 453||48 weeks of peg-IFN plus weight-based ribavirin||56%|
|Manns et al.; Lancet 2001||HIV-negative, chronic HC V; N = 511||48 weeks of peg-IFN plus ribvairin||54%|
|Kamal et al.; Gastroenterology 2006||HIV-negative, acute HC V; N = 175||12 weeks of peg-IFN||87% overall||HCV treatment was initiated at 8, 12, or 20 weeks after onset of acute HC V; sustained virologic response (SVR) by timing of treatment initiation was 95% at week 8, 92% at week 12, and 76% at week 20|
|Wiegand et al.; Hepatology 2006||HIV-negative, acute HC V; N = 89||24 weeks of peg-IFN||71%||≥80% adherence to treatment increased SVR to 89%|
|Chung et al.; NEJM 2004||HIV-positive, chronic HC V; N = 66||48 weeks of peg-IFN plus ribavirin||27%||Low initial ribavirin dosing could have worsened response rates|
|Torriani et al.; NEJM 2004||HIV-positive, chronic HC V; N = 289||48 weeks of peg-IFN plus ribavirin||40%|
|Dominguez et al.; AIDS 2006||HIV-positive, acute HC V, N = 25||24 weeks of peg-IFN plus ribavirin||71%||14 people completed treatment and follow up at publication; 10/14 achieved SVR|
|Vogel et al.; Antivir Ther 2006||HIV-positive, acute HC V, N = 36||24-48 weeks of peg-IFN||61%||Longer treatment duration increased SVR|
End-stage liver disease from HCV coinfection is a leading cause of death among HIV-positive people in the United States and Western Europe. People with HIV/HCV coinfection have generally acquired both viruses from injection drug use with shared, unsterilized equipment or from contaminated blood products such as clotting factor (prior to 1987; clotting factor has been safe to use since then). Most of what we know about HIV/HCV coinfection comes from studies of people who were infected with HCV before they became HIV-positive. Given the reports of HCV outbreaks in HIV-positive men, information about how the virus behaves in people who have contracted HCV after being infected with HIV is important.
The 2009 Conference on Retroviruses and Opportunistic Infections (CROI), held in Montreal, offered a range of information on the transmission, progression, and treatment of acute HCV infection among HIV-positive men.
Sarah Fishman and colleagues provided a snapshot of sexual activity and drug use among a handful of HIV-positive gay men with acute hepatitis C in New York (N = 21) and the United Kingdom (N = 60). Most cases were in men under 35 years old; the majority had never injected drugs, although more than 65% had used poppers, and more than 35% had used cocaine and ecstasy within the past 12 months. Group sex and anal sex were common; more than 75% reported engaging in unprotected receptive anal sex, and more than 60% in unprotected insertive anal sex. Many respondents reported fisting (receptive 23–56%; insertive 33–73%).
Daniel Fierer and colleagues at Mount Sinai Hospital in New York City fear that hepatitis C may be more aggressive in people who are already HIV-positive. They discovered unexpectedly serious liver damage in 19 of 24 HIV-positive men whose livers were biopsied within a median of 4.3 months (range: a few weeks to over four years) after being diagnosed with acute hepatitis C. It is not known if any of these men had preexisting liver damage, since liver biopsy is not—and should not become—part of the standard clinical workup for HIV-positive people.
Many factors can cause or contribute to liver damage, including HIV. Little is known about the prevalence, types, and extent of liver damage among HIVpositive people, though some information is available from a small study of HIVpositive people without underlying liver disease. Morse and colleagues performed liver biopsy and other tests on 24 people who had persistently elevated liver enzyme levels. They found serious liver disease in 35%, but no link with duration of HIV infection or length of time on antiretroviral therapy.
U.S. HIV treatment guidelines recommend HCV testing for all HIV-positive people. Unfortunately, guidelines don’t mention HCV risk assessment or routine and episodic testing unless triggered by elevated liver enzyme levels. Despite expert medical recommendations (from treatment and prevention guidelines), HC V screening has not been consistently incorporated into clinical practice. Karen Hoover and colleagues looked at viral hepatitis screening rates at six U.S. clinics in 2006–2007. They reported that less than 50% of 1,607 HIV-positive gay men were screened for hepatitis C during this period.
Fortunately, HCV treatment is more likely to work if it is initiated during the acute phase (within six months of HCV infection), regardless of HIV status (see table on page 4, “Response to HCV Treatment by HIV Status and in Acute versus Chronic Infection”). Fierer and colleagues reported that 8 of 15 HIVpositive men who initiated HCV treatment during acute infection were able to cure their HCV with treatment (one person remains on treatment; three others have just completed HCV treatment, and one person was lost in follow-up).
However, acute hepatitis C often goes undetected. It is rarely symptomatic and can be tricky to diagnose, since a group of tests are necessary to distinguish acute HCV from chronic HCV. An alert doctor, however, may suspect acute HCV if sudden spikes in alanine aminotransferase (a liver enzyme) are detected during routine monitoring of HIV-positive patients.
Unfortunately, HCV treatment has serious side effects, and this leads people to refuse or discontinue treatment even when offered during acute infection—when it is most likely to be effective.
Although improvements in HCV treatment are anticipated in the near future, pegylated interferon and ribavirin will still be the backbone. New drugs may shorten the course of treatment and increase response rates, but poor tolerability and significant expense will continue to limit treatment uptake. Thus, preventing new infections—or at least diagnosing them promptly and offering treatment when it is most likely to be successful—is warranted. Clearly, a public health strategy that includes messages about HCV sexual transmission and risk reduction for HIVpositive men who have sex with men is needed. Clinicians need to perform routine risk assessments, provide testing when indicated, and offer HCV treatment during acute infection until the current standard of care improves.
Fierer D, Fishman S, Uriel A, et al. (abstract 802). Characterization of an outbreak of acute HCV infection in HIV-infected men in New York City. 16th CROI, February 8–11, 2009, Montreal.
Fishman S, Childs K, Dieterich D, et al. (abstract 801). Age and risky behaviors of HIV-infected men with acute HCV infection in New York City are similar, but not identical to, those in a European outbreak. 16th CROI, February 8–11, 2009, Montreal.
Hoover K, Butler M, Tao G, et al. (abstract 803). Hepatitis Screening of HIV-infected men who have sex with men at eight U.S. clinics. 16th CROI, February 8–11, 2009, Montreal.
Morse C, Jones A, McLaughlin M et al. (abstract 748). High prevalence of hepatic fibrosis and steatosis in HIV/ AIDS patients without chronic viral hepatitis but with chronically elevated transaminases on ART. 16th CROI, February 8–11, 2009, Montreal.