The use of trough ribavirin concentration to predict sustained virological response and haematological toxicity in HIV/HCV-co-infected patients treated with ribavirin and pegylated interferon.

OBJECTIVES: To study the association between trough ribavirin concentration (C(trough)) with sustained virological response (SVR) and haemoglobin (Hb) decrease in HIV/hepatitis C virus (HCV)-co-infected (HIV+/HCV+) patients treated with anti-HCV therapy. METHODS: HIV+/HCV+ patients treated with ribavirin and pegylated interferon were prospectively evaluated. Qualitative and quantitative HCV-RNA, Hb levels and ribavirin C(trough) were measured at baseline and weeks 2, 4, 12, 24, 36 and 48 during therapy. HCV-RNA was also measured at 24 weeks after the end of therapy. Efficacy analysis was performed on patients with a definitive virological outcome (SVR, relapser and non-responder), whereas for toxicity analysis, dropouts were considered until the last available observation. RESULTS: Fifty-two patients (54.7% with genotype 1 or 4) were included. Overall, no correlation between ribavirin C(trough) and early virological response (EVR) nor SVR was found. However, in patients with genotype 1 or 4, ribavirin C(trough) was independently associated with EVR (P = 0.036) and SVR (P = 0.046). A ribavirin C(trough) cut-off of 1600 ng/mL was found to be associated with both EVR (chi(2) = 5.69, P = 0.028) and SVR (chi(2)=4.2, P = 0.04). Higher ribavirin C(trough) correlated with Hb decrease (R = -0.361, P = 0.009) and was independently associated with an Hb decrease of >4 g/dL (P = 0.009). Receiver operating characteristic (ROC) analysis indicated that a ribavirin C(trough) of >2300 ng/mL was associated with an Hb decrease of >4 g/dL (chi(2) = 8.08, P = 0.01). CONCLUSIONS: Our study confirmed a relationship between ribavirin exposure and both efficacy and toxicity. Moreover, we found ribavirin C(trough) cut-offs for both SVR in genotypes 1 and 4 and overall haematological toxicity. These findings deserve further clinical evaluation.

Cryoglobulinemia-related vasculitis during effective anti-HCV treatment with PEG-interferon alfa-2b.

HCV infection may be related to many extrahepatic manifestations including mixed cryoglobulinemia (MC). Clinical manifestations commonly associated to MC include arthralgia, purpura, vasculitis, peripheral neuropathy and renal function abnormalities. Treatment with interferon often leads to remission, especially in virological responders, or to disappearance of MC-related clinical manifestations. We report on a patient with chronic hepatitis C, deficit of G6P-DH, type II MC, who developed a cryoglobulinemic vasculitis with purpura, renal impairment and arterial hypertension, during treatment with PEG-interferon a-2b plus amantadine. The occurrence of purpuric lesions and MC-related nephropathy with increased cryocrit despite negative viremia, in a patient previously asymptomatic, during interferon treatment, is unusual.

Antiretroviral activity of pegylated interferon alfa-2a in patients co-infected with HIV/hepatitis C virus.

OBJECTIVES: To evaluate the early anti-HIV activity of pegylated interferon (PEG-IFN) alfa-2a and ribavirin in HIV/hepatitis C virus (HCV) co-infected patients not receiving antiretroviral therapy. PATIENTS AND METHODS: In 19 patients with baseline plasma HIV load (HIV-RNA) >1000 copies/mL treated with PEG-IFN alfa-2a and ribavirin, HIV-RNA and T-cell subsets were measured at baseline and 2, 4 and 12 weeks after initiation of anti-HCV therapy. RESULTS: We observed a significant HIV-RNA decrease (>1 log(10) copies/mL) through week 12 of anti-HCV treatment. The magnitude of HIV-RNA decline was associated with baseline HIV-RNA, CD4 count and PEG-IFN weight-adjusted dose. CONCLUSIONS: A significant early anti-HIV activity of PEG-IFN alfa-2a was observed. Such an effect warrants further clinical evaluation in the management of co-infected patients.