The Body Covers: The 39th Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy
Poster Session 9.H: Virus-HIV Coinfections
September 26, 1999
Two posters addressed the treatment of patients coinfected with HIV and Hepatitis C virus. Both studies used Interferon Alpha 2b and Ribavirin.Abstract: Interferon (IFN) and Ribavirin (RBV) Therapy for Hepatitis C (HCV) in HIV-Coinfected Patients (Paper 105)
Landau, et al. treated 20 coinfected patients, who had detectable HCV RNA and histologic evidence of fibrosis on liver biopsy. Patients were excluded if they had circulating HBsAg, daily EtOH of >40 gm, hemolytic disease, decompensated cirrhosis, autoimmune hepatitis, pregnancy or an opportunistic infection diagnosed within 6 months prior to the study.
Patients received 3 mil units of IFN alpha 2b three times per week (TIW) with Ribavirin 1000 mg (for body weight <75 kg) or 1200 mg (for body weight >75 kg) per day.
After 6 months, 10 patients (50%) had no detectable HCV RNA, with 7 undetectable as of 3 months. Two of the 10 responders were previous nonresponders to IFN monotherapy and 1 patient had relapsed after responding to IFN monotherapy. All patients completed 24 weeks of therapy.
These responses are not that different from those in HIV negative subjects. There was no sign of changes in CD4% or viral load of HIV. Absolute CD4 counts were decreased slightly, which the authors felt suggested that cells became trapped in extravascular sites.
Dieterich, et al. evaluated IFN 3 million units TIW alone and then in combination with Ribavirin. 11 received RBV and IFN combination. 10 received IFN alone for 3 months, and then combination therapy. Patients had abnormal liver biopsies. Median CD4 count was 348, mean viral load was 56,844. 11/21 patients had HIV RNA levels <400. 19/21 patients were receiving HAART, all with either d4T or AZT.
At 3 months in the IFN group median HCV RNA decreased 2.65 X 106 copies/ml, CD4 count increased fom 211 to 275 cells/mm3, and HIV RNA fell from 1500 to <400. At 3 months the patients on combination therapy had decreased median HCV RNA of 4.5 X 106 copies/ml, with 4/8 undetectable (<400), but median CD4 declined from 529 to 277. At 6 months 5/7 patients had undetectable HCV viral loads.
The main adverse event in this cohort was anemia in 5/21 patients, which was treated with erythropoietin. 2 patients discontinued interferon alone and 3 in the IFN/RBV group disconinued due to adverse events, 4/5 for constitutional symptoms, 1/5 for anemia.
Both studies presented small groups of patients. In both cases therapy in coinfected patients was safe, with no increase in HIV-RNA levels noted. There has been some concern about using Ribavirin with nucleoside analogues, especially thymidine analogues like AZT and d4T. This is based on in vitro studies done in the 1980's, which showed competitive inhibition of AZT in combination with Ribavirin. These studies were never correlated clinically and they signalled the end of trials looking for any anti-HIV activity of RBV. There is no indication of background HIV therapy in the first cohort, but Dieterich's patients are clearly on thymidine analogue drugs, so this is reassuring.
Both of these studies demonstrate efficacy of the IFN/RIB combination in decreasing hepatitis C viral load, at least in some patients. Again, the combination seems safe in patients with HIV, although we do not have the full details of patients' antiviral regimens. Still, better therapies are needed as the epidemic of HCV continues to worsen. A 50% response rate will not be enough to stop the spread of this disease.
Abstract: Efficacy of Combination Therapy with Interferon-Alpha 2b and Ribavirin for Chronic Hepatitis C in HIV-Infected Patients (Paper 104)
Authored by: D. Dieterich, et al.
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