Low dose pegylated interferon is ineffective in treating HIV/HCV co-infected patients

Due to the toxicity and tolerance issues surrounding the use of interferon, the temptation arises to try to use doses lower than those that have been proven to be effective.

In a study presented at the 41st ICAAC, investigators evaluated the safety and efficacy of 48 weeks of low-dose PEG-Intron (pegylated interferon alfa-2b), 50 mcg weekly, and ribavirin (RBV), 800 mg/day, combination therapy in the treatment of chronic hepatitis C virus (HCV) infection in patients coinfected with HIV and HCV.

This open-label, prospective study enrolled 35 patients with a median HIV viral load, HCV viral load and CD4+ T cell count of 1.7 log10 copies/mL, 9 x 105 IU/mL and 544 cells/mm3, respectively. 32 of the patients were on antiretroviral therapy. The most frequent genotypes were 1a (8 patients), 1b (10 patients), 2a (2 patients), and 3a (11 patients).

The primary endpoint of the study was a sustained virological response, ie, no detectable HCV RNA six months after the completion of combination therapy, but preliminary 24 week treatment results were presented.

At the end of 24 weeks, 33.3% of the patients were HCV RNA negative, and 55% of the patients had a biochemical response, ie normalized transaminases levels. As expected from previous studies, the response at the 3rd month of therapy was predictive of response at the 6th month of therapy (66% vs. 8%, p=0.02).

Toxicities included influenza-like-illness (88%), tiredness (82%), local inflammatory reaction (28%), headache (20%), cytopenias (17%), and depression (14%). Treatment had to be discontinued in five patients due to toxicities or intolerance. Contrary to another study presented at the December 2001 ICAAC and a study presented at the November 2001 AASLD meeting, there were no apparent interactions in toxicity between the HCV and HIV therapies.

While the median CD4+ T cell count declined to 347 cells/mm3 (likely due to the marrow suppressant effect of interferon), HIV viral loads were maintained or decreased in all patients.

The authors conclude: “Low dose Peg-IFN-alpha in combination with [ribavirin] is safe in HIV [patients] with chronic hep C, including those who receive ARV drugs. A poor response (33%) has been observed at week 24. This result suggests the need of use of higher doses in these patients.”

Thus, until some data clearly show otherwise, in HIV/HCV co-infected patients PEG-Intron should be dosed as directed, generally at 1.5 mcg/kg/week.

L Moreno and others. Early Response to Combination Therapy with Low-Dose Pegylated Interferon-Alpha (Peg-IFN) 2b and Ribavirin for Chronic Hepatitis C in HIV-Infected Patients. Abstract: H-458.