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Response-adjusted alpha-interferon therapy for chronic hepatitis C in HIV-infected patients
T Prestileo1, G Mazzola, F Di Lorenzo
1Division Malattie Infettive, Ospedale Casa del Sole, Palermo, Italy.
Insights
Tailoring alpha-interferon (IFN) dosage for chronic hepatitis C and HIV coinfection did not eradicate HCV. While IFN temporarily suppressed viral load and liver inflammation, dose adjustments did not improve long-term outcomes in most patients.
Area of Science:
- Hepatology
- Infectious Diseases
- Virology
Background:
- Standard alpha-interferon (IFN) therapy shows unsatisfactory response rates in patients coinfected with chronic hepatitis C (HCV) and HIV.
- HCV/HIV coinfection presents unique challenges due to complex disease interactions and treatment considerations.
Purpose of the Study:
- To evaluate the efficacy of adjusting IFN dosage based on HCV viral load response in coinfected patients.
- To determine if tailored IFN dosing can achieve sustained viral clearance or improve treatment outcomes.
Main Methods:
- Forty-one patients with chronic HCV/HIV coinfection received IFN (alphan1 interferon) starting at 3 MU tiw, with a dose increase to 6 MU tiw at 4 weeks if HCV-RNA drop was <50%.
- Patients were assessed for viral load, ALT levels, and treatment response at 24 weeks, with a 24-week post-therapy follow-up.
- HIV viral load and CD4 counts were also monitored during IFN therapy.
Main Results:
- IFN therapy led to marked, temporary reductions in ALT and HCV-RNA levels by week 4, sustained up to 24 weeks.
- Only one patient achieved a complete end-of-treatment response, with all others relapsing to baseline levels post-therapy.
- HIV viral load showed a slight reduction, while CD4 counts remained unaffected; 14 patients discontinued treatment early.
Conclusions:
- Increasing IFN dosage does not lead to HCV eradication in most HIV-coinfected individuals, even with controlled HIV.
- IFN temporarily suppresses HCV viraemia and liver inflammation, but the clinical significance of these surrogate markers for disease progression and survival remains uncertain.
Abstract:
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.