Large numbers of HIV-positive patients coinfected with hepatitis C virus who have advanced liver fibrosis experience severe side-effects when they receive the recommended hepatitis C therapy of interferon and ribavirin (Copegus / Rebetol / Virazole), according to a presentation to the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington. The investigators also found that at the end of treatment, only a minority of patients had a sustained virological response to treatment.
Therapy with interferon (particularly in its pegylated form) and ribavirin has become the standard of care for the treatment of hepatitis C virus infection. However, in individuals who are only infected with hepatitis C and have advanced liver fibrosis (stages F3 or F4, cirrhosis), it is associated with high rates of toxicity and has little therapeutic benefit.
Investigators wished to determine the safety and efficacy of treatment with interferon and ribavirin in HIV-positive patients coinfected with hepatitis C virus who had advanced fibrosis or cirrhosis.
A total of 56 patients were prospectively studied for the duration of treatment with interferon and ribavirin, with data on sustained virological response and death provided for a year after treatment was finished.
In total, 18% of individuals were diagnosed as having AIDS, 80% were male, 95% had a history of injecting drug use, and 88% were taking highly active antiretroviral therapy (HAART), which was controlling HIV infection in the majority of patients. On entry to the study, the median CD4 cell count was 435 cells/mm3 and median viral load was 50 copies/ml, the limit of detection of the most commonly used testing assays.
As regards hepatitis C virus, the median duration of infection was 20 years, liver biopsies revealed that 43% of patients had cirrhosis, and the majority of patients, 59%, were infected with hepatitis C genotype 1, which responds least well to currently available hepatitis C therapy.
Hepatitis C therapy was provided for a median of 36 weeks (range three weeks to 61). In accordance with currently accepted standards of treatment, 79% of patients received pegylated interferon (Pegasys / PegIntron / ViraferonPeg).
At the end of treatment 29% of patients had achieved a virological response, but only 14% sustained this response for one year. Side-effects associated with hepatitis C treatment were very common, with 29% of patients terminating therapy because of adverse events. During treatment, 20% of patients required admission to hospital and two patients (4%) died. In the year after finishing hepatitis C therapy a further four (7%) individuals also died.
Investigators also noted that there was a high rate of bacterial infections amongst patients (9%), and that significant numbers of individuals started drug use again during hepatitis C treatment (7%). Laboratory abnormalities were also widespread. In total 38% of patients became anaemic, requiring the adjustment of ribavirin treatment in 27% of patients and ribavirin cessation in 4%. Neutropenia was observed in 73% of patients, although only 7% of patients had to adjust their interferon dose because of this. Although usually mild and not treatment limiting, thrombocytopenia was seen in 61% of patients.
“Interferon and ribavirin produces significant toxicity and a low rate of sustained virological response” in patients co-infected with HIV and hepatitis C virus with advanced fibrosis, conclude the investigators. However, given that it has a favourable response in a small number of individuals, they believe that it could still be an important option for patients whose only other treatment option is liver transplantation.
Moreno L et al. Outcome and safety of IFN/RBV in HCV/HIV coinfected patients with advanced fibrosis 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, abstract V-784, 2004.