Sexual Transmission of Hepatitis C among HIV Positive Men in the U.S. and Australia

Nearly three-quarters of new hepatitis C virus (HCV) infections among HIV positive gay and bisexual men in the U.S. are likely due to sexual transmission, according to an analysis described in the January 31, 2011 advance online issue of Clinical Infectious Diseases. An Australian study published in the same issue found that sexual transmission accounted for a majority of cases among men who have sex with men, but injection drug use also played a role. These findings suggest that HIV positive people who have risky sex should undergo regular hepatitis C testing.

For the past decade researchers have reported outbreaks of apparently sexually transmitted acute hepatitis C among HIV positive men who have sex with men in cities in Europe, Australia, and the U.S. HCV infection has been linked to fisting, unprotected anal intercourse, group sex, having multiple partners, use of non-injected recreational drugs, and presence of other sexually transmitted diseases.

It is estimated that approximately one-third of HIV positive people also have HCV. Coinfected people tend to experience more rapid liver disease progression and do not respond as well to hepatitis C treatment. Currently, however, many people with HIV do not routinely receive HCV screening, and hepatitis C often has no symptoms until advanced stages of liver disease.

U.S. Study

In the first study, Lynn Taylor from Brown University and colleagues analyzed HCV incidence (new infections) during 1996-2008 among men participating in the AIDS Clinical Trial Group Longitudinal Linked Randomized Trials (ALLRT) cohort, made up of people taking part in selected HIV treatment trials.

The researchers evaluated associations between hepatitis C and self-reported injection drug use, CD4 T-cell count, and HIV RNA viral load. Given the retrospective nature of the study, however, information on sexual activity and HCV risk factors other than injection drug use was unavailable.

Results

• A total of 1830 men who initially tested HCV negative had at least 1 subsequent HCV antibody test.
• At the time of the initial negative HCV test, 94% of the men were receiving combination antiretroviral therapy (ART).
• 6% were current or prior injection drug users (IDUs).
• 36 men experienced HCV seroconversion during an average 3-year follow-up period, for an overall incidence rate of 0.51 cases per 100 person-years.
• The average age at the time of HCV seroconversion was 46 years.
• As expected, HCV seroconversion was significantly associated with injection drug use (25% of seroconverters vs 5% of non-seroconverters).
• However, 75% of seroconverters (27 men) reported no history of drug injection.
• HCV incidence rates were 2.67 cases per 100 person-years among IDUs, compared with 0.40 cases per 100 person-years among non-IDUs.
• HCV seroconversion was associated with HIV RNA > 400 copies/mL, but there was no observed link between seroconversion and CD4 cell count.

"Incident HCV infection occurs in HIV-infected men involved in U.S. HIV therapeutic trials, primarily through non-parenteral [injection] means," despite engagement in care and use of ART, the study authors concluded.

They added that, "HCV antibody development was not related to immune status but was associated with inadequate HIV suppression."

Australia Study

In the second study, Gail Matthews and fellow investigators with the Australian Trial of Acute Hepatitis C (ATAHC) Study Group looked at the overlap between hepatitis C epidemics attributed to injection drug use and sexual transmission.

The trial enrolled 163 individuals with recent HCV infection, of whom 29% were already HIV positive. The researchers analyzed HCV genetic sequences (E1/HVR1) and constructed phylogenetic trees to show clusters of infection caused by the same or related virus strains.

Results

• 73% of HCV infections were attributed to injection drug use.
• Sexual transmission accounted for only 18% of HCV infections overall, or 29 cases:
  • 23 cases, or 92%, were HIV positive people, all of them gay/bi men.
  • 2 HIV negative men had probable sexually transmitted HCV, one of whom reported sex with another man and the other only with women.
  • 4 cases were women with HCV positive male partners.
• Among 112 individuals with available genetic sequence data, 23 (20%) were infected with an HCV strain identical to that of another participant.
• HCV infections could be groups into 4 homologous (related) clusters and 3 monophyletic (identical) pairs.
• The majority of clustered infections (78%) occurred in HIV positive people, while just 8% of HIV negative people could be placed in one of these transmission clusters.
• About half of gay/bi men could be placed in clusters, and all but 1 cluster included men who have sex with men.
• Clusters included individuals infected through both injection drug use and sexual transmission.

Based on these results, the investigators concluded, "This large unique study of HIV-infected and HIV-uninfected individuals with recently acquired HCV infection demonstrates that clustering is common in the HIV-infected population and that it occurred almost invariably among men who have sex with men, irrespective of the actual mode of acquisition."

"[Injection drug use] remains overwhelmingly the most common mode of [HCV] infection among HIV-uninfected populations but is less common than sexual transmission among HIV-infected populations," they elaborated. "In this group, both IDU-related and sexual exposures occur and are involved as mechanisms of transmission in the same social networks, which appear to be based on sexual orientation rather than specific risk-taking behavior."

Taken together, the 2 studies suggest that HIV positive people, especially men who have sex with men, should receive regular HCV screening. This could reduce new infections by encouraging safer sex practices, and hepatitis C treatment during the acute stage when it is much more likely to produce a cure.

Investigator affiliations:

Taylor study: Department of Medicine, Brown University, Providence, RI; Department of Medicine, Stanford University, Stanford, CA; Statistical & Data Analysis Center, Harvard School of Public Health, Boston, MA; Department of Medicine, University of California San Diego, La Jolla, CA; Department of Medicine, Ohio State University, Columbus, OH; Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH.

Matthews study: National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia; Kirketon Road Centre; Virology Division, SEALS Microbiology, Prince of Wales Hospital; Centre for Infection and Inflammation Research, University of New South Wales, Sydney, University of New South Wales; Burnet Institute, Melbourne, Australia.

2/11/11

References

LE Taylor, M Holubar, K Wu, and others. Incident hepatitis C virus infection among US HIV-infected men enrolled in clinical trials. Clinical Infectious Diseases (abstract). January 31, 2011 (Epub ahead of print).

GV Matthews, and others. Patterns and characteristics of hepatitis C transmission clusters among HIV-positive and HIV-negative individuals in the Australian Trial of Acute Hepatitis C. Clinical Infectious Diseases (abstract). January 31, 2011 (Epub ahead of print).

Other Source

Clinical Infectious Diseases. Study Examines Incident Hepatitis C Infection in HIV-Infected Men. News release. February 1, 2011.