Important note: Information in this article was accurate in November 2000. The state of the art may have changed since the publication date.
Therapy for hepatitis C virus (HCV) infection is currently limited to a combination of the nucleoside analogue ribavirin and the immune booster interferon-alpha. In non-HIV-infected people who have HCV, up to 40% recover when treated with this combination. In people co-infected with both viruses, recovery rates are usually much lower.
Doctors treating HIV and HCV co-infected patients have a number of concerns, including the safety of combination therapy for HCV. As well, there's also the possibility that ribavirin may weaken the anti-HIV activity of nukes such as AZT and d4T. To try and resolve some of these concerns, doctors in Paris, France, reviewed the medical records of 21 people co-infected with HCV and HIV who had been given combination therapy for HCV. All of these people had been unsuccessfully treated for HCV with interferon in the past, so perhaps it is not surprising that only 14% experienced a sustained recovery from HCV when later given the combination of interferon and ribavirin. Side effects were experienced though largely tolerated (see the report below for further details). Further research is needed on more effective and better-tolerated therapies for HCV infection.
Doctors reviewed the medical records of 21 subjects (4 female, 17 male), all of whom had both HCV and HIV. About half the group had liver damage due to HCV infection. Twelve subjects were taking anti-HIV therapy that included a protease inhibitor. For almost one year, all subjects received interferon at a dose and schedule of 3 million units three times weekly and 1,000 to 1,200 mg/day of ribavirin. Before receiving combination therapy for HCV infection, subjects had the following basic lab values:
The average (HIV) viral load of subjects did not change significantly during the study. Three people did, however, have a significant increase in viral load. It is important to note that before starting interferon-ribavirin the viral loads of these three subjects were below the 200 copy mark.
Red blood cell levels fell significantly during the study, likely an effect of ribavirin. In one person, red blood cell levels decreased so much that doctors stopped further therapy with interferon-ribavirin. This complication caused doctors to reduce the dose of ribavirin in one subject and to give a blood transfusion to another.
After three months of anti-HCV therapy CD4+ counts fell by 68 cells in 52% of subjects. After six months, the average decrease was about 57 cells. One subject had to stop interferon-ribavirin because of falling CD4+ counts and rising viral load. Once therapy was stopped, viral load fell.
According to the doctors, no other "serious" side effects were observed in study subjects. Three months after subjects ended their therapy, red blood cell and CD4+ cell counts rose significantly.
A total of six subjects (29%) appeared to have recovered from HCV infection at the end of therapy. But six months after they stopped taking interferon-ribavirin HCV levels became detectable in three of those subjects. Thus, only three of 21 subjects (14%) ultimately recovered. Details about which type of HCV and how this might have been linked to recovery from infection were not provided by the researchers.
Based on the results of their review, the French researchers think that ribavirin had a limited impact on the effectiveness of AZT and d4T. Readers should note that since the study was not designed to investigate such interactions, the researchers cannot be certain about this conclusion. It is important to note that when one subject stopped taking interferon-ribavirin, his/her HIV viral load fell.
Data from this study suggest that better therapies against HCV are needed. The recovery rate from HCV infection in this study of co-infected subjects was a dismal 14%. Yet the seriousness of the complications that arise from co-infection with HCV in HIV+ people makes a strong case for the early treatment of HCV infection in this population.
1. Zylberberg H, Benhamou Y, Lagneaux JL, et al. Safety and efficacy of inteferon-ribavirin combination therapy in HCV-HIV co-infected subjects: an early report. Gut 2000;47(5):694-697.
2. Mutimer D. Management of the HIV-HCV co-infected patient. Gut 2000;47(5):608-609.
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