New HCV Infection Is Occurring among HIV Positive U.S. Men, ACTG Analysis Shows

		SUMMARY: The incidence of hepatitis C virus (HCV) infection may be increasing among HIV positive men in the U.S., according to an analysis of participants in several AIDS Clinical Trial Group (ACTG) studies presented this past weekend at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston. Only 25% reported injection drug use, suggesting that non-parenteral routes (for example, sexual transmission) play a significant role.

By Liz Highleyman

Beginning around 2002, clinicians in the U.K. began reporting outbreaks of apparently sexually transmitted acute HCV infection among men who have sex with men. Only a small percentage reported a history of drug injection, and genotypic analyses showed that case clusters reflected sexual networks. Though not entirely consistent from study to study, identified risk factors have included fisting, use of sex toys, group sex, sex in public venues such as bathhouses, other sexually transmitted infections, and use of non-injected recreational drugs.

Similar outbreaks have since been reported in several large cities in Europe, in Australia, and in a few cities in the United States (e.g., New York City, San Francisco). The U.S. cases, however, have yet to receive the same attention as the European clusters, and the extent of the epidemic nationwide is not known.

To shed further light on this issue, researchers from Brown University and Harvard School of Public Health performed an analysis of HCV incidence among men participating in the ACTG Longitudinal Linked Randomized Trials (ALLRT) cohort, a long-term follow-up study of HIV positive individuals enrolled in selected ACTG clinical trials in the U.S.

A total of 17 ACTG studies performed HCV antibody testing from 1996 through 2002. Starting in 2002, HCV antibody screening was done at entry into the ALLRT cohort. Beginning in 2006, repeat testing was carried out every 96 weeks.

The investigators identified 2365 HIV positive male participants who had an initial negative HCV antibody test result. Within this group, 1830 men who received at least 1 subsequent HCV test were included in an analysis of seroconversion rates, contributing more than 7000 total person-years.

In this subgroup, the average age at the time of the first HCV test was 42 years (range 17-79), and 52% were over age 40. A majority (57%) of the men were white, 22% were black, and 18% were Hispanic. Almost all (94%) were on highly active antiretroviral therapy (HAART).

To control for increased surveillance and the fact that follow-up testing intervals changed over the course of follow-up, the date of HCV seroconversion was designated as being halfway between the last negative antibody test and the first positive test. Follow-up durations varied, but nearly half the participants (47%) were followed for more than 4 years.

The researchers evaluated associations between self-reported injection drug use (IDU) -- 0.5% reported current use and 5.3% reported past use -- CD4 cell count, and HIV viral load. However, data about sexual or other non-IDU risk factors were not available.

Results

	36 initially HCV negative men seroconverted during follow-up, for an overall incidence of 0.51 per 100 person-years.
	The mean age at the time of HCV seroconversion was 46 years (range 22-69), and 72% were over age 40.
	Injection drug use was a significant predictor of HCV seroconversion.
	25% of men who became infected with HCV reported injection drug use, compared with 5% of non-seroconverters (P < 0.001).
	However, 75% of HCV seroconverters had no history of drug injection.
	HCV incidence was 2.67 per 100 person-years among injection drug users compared with 0.40 among non-IDUs.
	HCV seroconversion was associated with having HIV viral load > 400 copies/mL (44% at the time of HCV positive antibody test vs 21% at the time of last negative HCV test; P < 0.001).
	HCV infection was not, however, linked to CD4 cell count.

"Incident HCV infection is occurring in a U.S. HIV positive male population despite engagement in care with HAART, potentially through non-parenteral means," the investigators concluded. "HCV antibody development was not related to immune status, but was associated with inadequate HIV suppression."

Medicine, Brown University, Providence, RI; Statistical & Data Analysis Center, Harvard School of Public Health, Boston, MA.

11/06/09

Reference
M Holubar, LE Taylor, K Wu, and others. Hepatitis C virus (HCV) antibody seroconversion in a U.S. HIV-infected male clinical trials population. 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract LB14