Response-adjusted alpha-interferon therapy for chronic hepatitis C in HIV-infected patients.
In patients with chronic hepatitis C and HIV infection, responsiveness to the standard schedule of alpha-interferon (IFN) is unsatisfactory. To quantify the effectiveness of tailoring IFN dosage according to HCV viral load under treatment, we enrolled 41 patients (M/F 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+/-4 years, and had clinical and histological evidence of chronic hepatitis (10% with cirrhosis). The CDC stage was A1 in five, A2 in 14, A3 in eight, B2 in eight, B3 in three and C3 in three. Twenty four patients were on triple therapy with protease inhibitors, 11 were on two-drug anti-HIV regimens and three were untreated. IFN (alphan1 interferon) was started at 3 MU tiw and increased at 6 MU tiw at 4 weeks if serum HCV-RNA had not dropped by at least 50%. IFN was stopped at 24 weeks in non-responders. Eleven patients received a dose increase (total IFN dose at 24 weeks 396 MU), while 16 did not increase the initial dose (total IFN dose at 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 4, and this reduction lasted up to 24 weeks. However only one patient had a complete biochemical and virological end-of-treatment response, which was maintained over a 24 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 therapy, 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 temporarily suppressed by IFN, but the relevance of these surrogate endpoints to progression of liver disease and to survival cannot be assessed.
Prestileo
T
T
Division Malattie Infettive, Ospedale Casa del Sole, Palermo, Italy.
Mazzola
G
G
Di Lorenzo
F
F
Colletti
P
P
Vitale
F
F
Ferraro
D
D
Di Stefano
R
R
Cammà
C
C
Craxì
A
A
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D005260:Female; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D010349:Patient Compliance; D019966:Substance-Related Disorders / Q000150:complications; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D016898:Interferon-alpha