Treatment Issues: Newsletter of Experimental AIDS Therapies - Volume 17, Number 7-8, July / August 2003
Tracy Swan

Two Viruses, One Clean Syringe and a Condom

Hepatitis C infection is prevalent among injection drug users around the world, and in the United States, as many as 90 percent of the people who acquired HIV from injection drug use also have hepatitis C virus (HCV). Overall, 16–25 percent of people with HIV in the U.S. are also coinfected with HCV. In China, 96 percent of HCV infections resulted from injection drug use and/or illegal blood donation; in Tunisia, injection drug use was reported by 83.7 percent of coinfected people, and in Brazil, male and female HIV-positive injection drug users were far more likely to be coinfected than people who acquired HIV from sex.

Overall, sexual transmission of hepatitis C appears to be low, but has been reported more frequently among men who have sex with men (MSM). In England, researchers have tracked cases of acute hepatitis C infections between 1997 and 2002 among a group of MSM. Of the 28 cases identified, 26 were in HIV-positive men, and 20/26 reported no risk factor other than unprotected anal intercourse. Another group of researchers in England identified 20 cases of acute HCV in HIV-positive men between October of 2002 and January of 2003. All 20 had had unprotected anal intercourse; 15 of the 20 reported fisting. Although the possibility of sexual transmission of HCV has been debated in the past, clearly, HCV prevention messages targeted specifically for MSM are now overdue.

As prevention, education and treatment programs for HIV begin to scale up in the developing world, the challenge of HCV must not be forgotten. At a minimum, access to clean injection equipment should be included in prevention and treatment initiatives. But scaling-up of prevention efforts is urgently needed here in the United States as well. Clean injection equipment must be readily available to all who need it in sufficient quantities with minimal legal and bureaucratic barriers to access. Imagine what would happen to the HIV infection rate be if obtaining protection required exchanging used condoms on a one-to-one basis!

HIV, HCV, Injection Drug use and Survival in the HAART era

End-stage liver disease has become a leading cause of death among HIV-positive people in Europe and the United States, and the liver damage caused by hepatitis C disease progresses more rapidly in HIV-positive people. One study found advanced liver disease among a third of 914 coinfected individuals, all of whom had a similar estimated duration of infection (16 years). Heavy alcohol intake and increased age (over 35) were the only variables associated with the progression of fibrosis, the tissue scarring that accompanies HCV infection.

A French group evaluated a decade of data from 2, 710 HIV-positive individuals, and analyzed the impact of HAART, HCV coinfection and injection drug use on survival before and after 1996. During the HAART era, five-year mortality rates were higher for coinfected people than for those with HIV alone, and higher yet for coinfected injection drug users. Although HCV coinfection did not significantly increase the risk of death at five years, coinfection plus injection drug use did, with the risk of death almost three times greater for coinfected injection drug users than for people with HIV alone.

These differences in survival may be attributed to several factors. Some studies have reported that coinfected people have a blunted immune response to HAART which might mean they are more susceptible to death from AIDS. Also, coinfected individuals are at greater risk for developing liver toxicity from antiretroviral therapy and they may experience more frequent switches or discontinuations of drug regimens. Access to treatment for HIV and HCV is a significant problem for coinfected injection drug users, who often receive HAART later than non-users. Until 2002, injection drug use was a contraindication for HCV treatment and although the 2002 Consensus Statement on Management of HCV has revised this recommendation, many physicians are still reluctant to treat injection drug users. Even when HCV treatment is prescribed, access is not guaranteed; under-funded AIDS Drug Assistance Programs can’t afford to add expensive HCV treatment to their formularies, leaving many coinfected people without a way to pay for HCV therapy, which costs as much as $40,000 for the 48-week course of treatment. These factors, plus the primary risks of using injection drugs probably all contribute to higher death rates for this vulnerable group.

Lack of access is not the only barrier to HCV treatment. Eligibility can be limited; a Spanish study reported that 60.6 percent of 1,006 coinfected individuals had contraindications for HCV treatment. Furthermore, the side effects of interferon and ribavirin may be especially severe in coinfected persons. In the studies presented at the IAS conference, the rate of treatment discontinuations ranged from 15 to 24 percent and adverse events reported included psychiatric toxicities, pancreatitis/lactic acidosis, hepatic decompensation, severe neutropenia, thyroid dysfunction and retinopathy.

HCV treatment does not appear to work as well in coinfected people regardless of CD4 cell count or HIV virus load. In one study, only 21 percent (28/132) of individuals treated for HCV achieved a sustained virologic response six months after completion of a 48-week course of standard interferon plus ribavirin. Disappointingly, with pegylated interferon and ribavirin, only 26 percent (15/58) of individuals achieved a sustained virologic response. The only predictive marker that has been significantly associated with sustained virologic response to treatment remains infection with HCV genotype 2 or HCV genotype 3.

References

Kilani B. Seroepidemiology of HCV-HIV Co-Infection in Tunisia. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 952.

Yin N. Epidemiology and Distribution of Human Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV) Among Intravenous Drug Users and Illegal Blood Donors in China. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 954.

Bhagani S. Acute HCV in a Cohort of HIV-Positive Homosexual Men in a London Clinic-Risk Factors and Outcomes. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 955.

Voirin N. Survival of Patients infected with HIV and HCV in the era of highly-active antiretroviral therapy. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 956.

Berenguer J. Interferon Alpha and Ribavirin Therapy for Chronic Hepatitis C in HIV-Infected Patients (GESIDA 28-02 Study). IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 960.

Njouom R. Seroprevalence of HCV Among HIV-Positive and HIV-Negative Pregnant Women in Yaounde, Cameroon. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 967.

Hernández S. Estimation of the HCV-HIV Co-Infected Population Eligible for Anti-Hepatitis C Treatment or Liver Transplant in Spain (GESIDA 28-02 Study). IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 970.

Parra-Ruiz J. IT78047 Trial. A Randomized, Multicentre Study of Pegylated Interferon Plus Two Different Does of Ribavirin in the Treatment of Patients with Chronic Hepatitis C and HIV Infection. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 971.

Browne RE. Increasing Incidence of Acute Hepatitis C in HIV Positive Men Secondary to Sexual Transmission: A New Epidemic? IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 972.

Hopkins S. HIV-HCV Co-Infection: To Treat or Not to Treat. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 973.
Msellati P. Prevalence of Hepatitis B and C Viruses and HCV Genotypes in HIV-Positive and Negative Pregnant Women in Abidjan, Ivory Coast (West Africa). IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 974.

Voigt E. Factors Related to Outcome of Treatment with Pegylated Interferon Alpha 2b (PEG INF) Plus Ribavirin (RBV) in HCV/HIV Co-Infected Patients. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 976.

Slim J. Neutropenia as an Adverse Drug Reaction in Patients Co-Infected with HIV/HCV Receiving Interferon and Ribavirin Therapy. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 977.
Sprinz E. Hepatitis C Virus Infection in a Southern Brazilian Cohort of HIV-Infected Patients. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 978.

Martin-Carbonero L. Fibrosis Progression in 914 HIV-HCV Co-Infected Patients is Strongly Related With Age: A European Collaborative Study. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 984.

Pacheco R. Clinical and Epidemiological Characteristics of Hepatitis C Infection in a Large Cohort of HIV-Infected Patients in Spain (GESIDA 29/02 Study). IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 985.

Birowo NR. Prevalence of HIV and HCV Co-Infection Among Drug Users. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 987.

Ngo-Giang-Huong N. HIV-1/HCV Co-Infection in Pregnant Women and Their Infants in Thailand. IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 994.

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