Response-adjusted alpha-interferon therapy for chronic hepatitis C in HIV-infected patients

In patients with chronic hepatitis C and HIV infection, responsiveness to t he standard schedule of alpha-interferon (IFN) is unsatisfactory. To quanti fy the effectiveness of tailoring IFN dosage according to HCV viral load un der treatment, we enrolled 41 patients (MIF 32/9) chronically coinfected by HCV and HIV with chronic liver disease. All were former i.v. drug addicts, with a mean age of 32 +/- 3 years, and had clinical and histological evide nce of chronic hepatitis (10% with cirrhosis). The CDC stage was Al in five , A2 in 14, A3 in eight, B2 in eight, B3 in three and C3 in three. Twenty f our patients were on triple therapy with protease inhibitors, 11 were on tw o-drug anti-HIV regimens and three were untreated. IFN (alpha n1 interferon ) was started at 3 MU tiw and increased at 6 h 1U tiw at 9 weeks if serum H CV-RNA had not dropped by at least 50%. IFN was stopped at 34 weeks in non- responders. Eleven patients received a dose increase (total IFN dose at 14 weeks 396 MU), while 16 did not increase the initial dose (total IFN dose a t 24 weeks 216 MU). Fourteen subjects stopped within the first weeks due to relapse of drug abuse (ten) or subjective intolerance (four). ALT and HCV- RNA levels were markedly decreased at week 3, and this reduction lasted up to 24 weeks. However only one patient had a complete biochemical and virolo gical end-of-treatment response, which was maintained over a 34 weeks post- therapy follow-up. All other patients relapsed to baseline ALT and HCV-RNA values after stopping IFN. HIV viral load was slightly reduced under IFN th erapy, while CD4 counts were unaffected. We conclude that raising the dose of IFN dose not eradicate HCV in most HIV-infected patients, even when HIV is well controlled by treatment. HCV viraemia and necroinflammation are tem porarily suppressed by IFN, but the relevance of these surrogate endpoints to progression of liver disease and to survival cannot he assessed. (C) 200 0 Published by Elsevier Science B.V. and international Society of Chemother apy. All rights reserved.