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HIV/HCV Coinfection Fell along with Injection Drug Use among Men in HOPS; WIHS Women Appear Prone to HCV Sexual Transmission

SUMMARY: Two recently published studies looked at the epidemiology of HIV/HCV coinfection in large, long-term cohort studies. Among men in the HIV Outpatient Study (HOPS), the HIV/HCV coinfection rate declined between 1996 and 2007, corresponding to a drop in the proportion of new HIV infections attributable to injection drug use. In the Women's Interagency HIV Study (WIHS), however, a considerable number of women who acquired hepatitis C virus (HCV) did not inject drugs but had partners who did, suggesting that sexual transmission occurs more often than previously assumed.

By Liz Highleyman


In thefirst study, described in the March 1, 2010 Journal of Acquired Immune Deficiency Syndromes, Philip Spradling from the Centers for Disease Control and Prevention (CDC) assessed HCV screening practices and determined trends in the prevalence of hepatitis C coinfection among 7618 HOPS participants -- mostly gay/bisexual men -- enrolled at 10 clinics in 8 U.S. cities.

The researchers calculated the proportion of study participants eligible to be tested for HCV -- that is, those who had never been tested before or were previously found to be HCV negative -- and looked at the annual prevalence of HCV infection from 1996 through 2007 according to socio-demographic, clinical, and HIV risk category characteristics.


The proportion of eligible cohort participants tested for HCV infection rose from 10.7% in 1996 to 76.6% in 2007, with increases seen in all demographic and risk groups.
Overall HCV prevalence decreased from 36.7% in 1996 to 19.7% in 2007.
Decreases in prevalence occurred among all groups except injection drug users.
In a multivariate analysis, the following factors were independently associated with an increased likelihood of having received an HCV test:
Age older than 35 years;
At least 3 years of participation in the HOPS cohort;
Non-white race;
Hispanic ethnicity;
Being in the high-risk heterosexual or injection drug user risk categories.

"Screening for HCV infection in the HOPS has improved, although a sizable fraction of patients remain unscreened," the study authors concluded.

They explained that the decline in overall HCV infection prevalence between 1996 and 2007 resulted primarily from a decline in the fraction of all prevalent infections in the cohort attributable to injection drug users.


In the second study, published in the November 20, 2009 issue of AIDS Patient Care and STDs, Toni Frederick and colleagues attempted to determine whether sexual transmission was a significant route of HCV transmission among women in the U.S. WIHS cohort.

Experts have traditionally thought that sexual transmission of HCV is uncommon overall, and studies of HIV negative monogamous heterosexual couples typically find transmission rates below 5%. Since around 2000, however, researchers have been reporting clusters of acute or recent HCV infection among mostly HIV positive gay/bisexual men, first in large European cities then in the U.S. and Australia. While there has been some variation among studies, commonly reported risk factors include "rough sex" (e.g., fisting), sex in group settings, sex while using non-injection club drugs, and concurrent sexually transmitted diseases (STDs).

Among men, having HIV seems to increases like likelihood that an individual will become infected with HCV, develop chronic infection (rather than spontaneous clearance), experience more rapid liver disease progression, and respond less well to interferon-based therapy. But these effects have not been extensively studied in women.

The present study included more than 3600 HIV positive and at-risk HIV negative women enrolled in WIHS from October 1994 to November 1995 and from October 2001 to November 2002. Demographic and clinical factors associated with HCV infection were assessed in a multivariate analysis controlling for history of injection drug use or blood transfusions.


Among 3636 women with available HCV test results, 31.5% were found to be HCV antibody positive.
This group included 13.5% who had no reported history of injection drug use or blood transfusions.
The prevalence of HCV infection among women with no reported history of injection drug use or blood transfusion was 6.5% -- 7.7% for HIV positive women and 3.6% for HIV negative women.
A multivariate analysis showed that among women with no history of injection drug use themselves, having sex with a man who was an injection drug user was an independent risk factor for HCV infection, after controlling for other factors including blood transfusions, age, HIV status, and hepatitis B infection (odds ratio [OR] 2.8).
Further stratification according to HIV status showed that the association was significant only for HIV positive women (OR 1.9) compared to HIV negative women (OR 1.1), although these odds ratios did not differ significantly.

Based on these findings, the WIHS investigators concluded, "For HIV positive women with no reported history of [injection drug use], sex with an [injection drug user] male was independently associated with HCV, suggesting that sexual transmission may be an important mode of HCV transmission for these high-risk women."

"While this study is cross-sectional, it is possible that HIV infection may play a role in increasing the likelihood of HCV sexual transmission because of a compromised immune system in the setting of continued high-risk sexual behaviors," they suggested in their discussion.

"Further study of the sexual practices of women with HIV and at risk for HIV may shed light on potential mechanisms of sexual transmission of HCV," the authors continued. "Like HIV, STDs may increase the risk of HCV transmission through ulcerative lesions, providing a portal of entry for HCV. Anal sex, intercourse during menstruation, and sex with physical trauma may also provide avenues for enhanced sexual transmission of HCV through exposure to blood."

"Among HIV-infected MSM [men who have sex with men], it has been suggested that high-risk sexual practices including anal fisting and sex in the presence of ulcerative coinfections are associated with HCV acquisition and may have fueled recent HCV outbreaks in this subgroup of MSM," they added. "These same mechanisms may be important for HCV transmission among HIV-infected women engaging in high-risk sexual practices."

HOPS: Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA.

WIHS: Maternal-Child and Adolescent Center for Infectious Diseases and Virology, Division of Hematology & Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA; Division of Gastroenterology, University of California at San Francisco, San Francisco, CA; Cook County Medical Center, Chicago, IL; State University at Downstate Medical Center, Brooklyn, NY; Georgetown University School of Medicine, Washington, DC; Johns Hopkins School of Public Health, Baltimore, MD; Bronx-Lebanon Hospital Center, Bronx, NY.



PR Spradling, JT Richardson, K Buchacz, and others. Trends in Hepatitis C Virus Infection Among Patients in the HIV Outpatient Study, 1996-2007. Journal of Acquired Immune Deficiency Syndromes 53(3): 388-396 (Abstract). March 1, 2010.

T Frederick, P Burian, N Terrault, and others. Factors Associated with Prevalent Hepatitis C Infection Among HIV-Infected Women with No Reported History of Injection Drug Use: The Women's Interagency HIV Study (WIHS). AIDS Patient Care and STDs 23(11): 915-923 (Abstract). November 20, 2010.























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