Erythrocyte and plasma ribavirin concentrations in the assessment of early and sustained virological responses to pegylated interferon-alpha 2a and ribavirin in patients coinfected with hepatitis C virus and HIV.

OBJECTIVES: To determine the relationship between erythrocyte and plasma ribavirin concentrations in hepatitis C virus (HCV)/HIV-coinfected patients, and to correlate ribavirin exposure with early and sustained virological response (EVR and SVR) and haemoglobin level reductions. METHODS: Clinical and biological data from 68 HCV/HIV-coinfected patients were recorded at baseline, week 4 (W4), week 12 and at 24 weeks after completion of treatment. Plasma and erythrocyte ribavirin concentrations were determined 12 h after the final ribavirin dose (C(min)). RESULTS: Erythrocyte ribavirin concentrations were 100-fold higher than plasma concentrations, with a significant relationship between them (P < 0.05). In patients with HCV genotype 1 or 4, a plasma ribavirin C(min) threshold of 1.95 mg/L at W4 tended to predict EVR [sensitivity 44%; specificity 87%; AUC 0.67 (95% CI 0.50-0.84)] and was predictive of SVR [sensitivity 58%; specificity 84%; AUC 0.71 (95% CI 0.51-0.90)]. Among patients with these HCV genotypes, an erythrocyte ribavirin C(min) threshold of 146 mg/L at W4 was found to be the best value for discriminating between responders and non-responders for both EVR [sensitivity 67%; specificity 75%; AUC 0.58 (95% CI 0.24-0.93)] and SVR [sensitivity 50%; specificity 80%; AUC 0.70 (95% CI 0.39-1.01)]. We also demonstrated a significant relationship between reduced haemoglobin levels and plasma ribavirin C(min) at W4 (P = 0.05). CONCLUSIONS: Therapeutic drug monitoring may be useful for the management of anti-HCV treatment in HCV/HIV-coinfected patients.

Treatment of acute hepatitis C in human immunodeficiency virus-infected patients: the HEPAIG study.

UNLABELLED: Acute hepatitis C continues to be a concern in men who have sex with men (MSM), and its optimal management has yet to be established. In this study, the clinical, biological, and therapeutic data of 53 human immunodeficiency virus (HIV)-infected MSM included in a multicenter prospective study on acute hepatitis C in 2006-2007 were retrospectively collected and analyzed. The mean hepatitis C virus (HCV) viral load at diagnosis was 5.8 ± 1.1 log(10) IU/mL (genotype 4, n = 28; genotype 1, n = 14, genotype 3, n = 7). The cumulative rates of spontaneous HCV clearance were 11.0% and 16.5% 3 and 6 months after diagnosis, respectively. Forty patients were treated, 38 of whom received pegylated interferon and ribavirin. The mean duration of HCV therapy was 39 ± 17 weeks (24 ± 4 weeks in 14 cases). On treatment, 18/36 (50.0%; 95% confidence interval 34.3-65.7) patients had undetectable HCV RNA at week 4 (RVR), and 32/39 (82.1%; 95 confidence interval 70.0-94.1) achieved sustained virological response (SVR). SVR did not correlate with pretreatment parameters, including HCV genotype, but correlated with RVR (predictive positive value of 94.4%) and with effective duration of HCV therapy (64.3% for 24 ± 4 weeks versus 92.0% for longer treatment; P = 0.03). CONCLUSION: The low rate of spontaneous clearance and the high SVR rates argue for early HCV therapy following diagnosis of acute hepatitis C in HIV-infected MSM. Pegylated interferon and ribavirin seem to be the best option. The duration of treatment should be modulated according to RVR, with a 24-week course for patients presenting RVR and a 48-week course for those who do not, irrespectively of HCV genotype.

Efficacy and safety of adefovir dipivoxil plus pegylated interferon-alpha2a for the treatment of lamivudine-resistant hepatitis B virus infection in HIV-infected patients.

BACKGROUND: Up to 10% of the HIV-positive population is coinfected with hepatitis B virus (HBV). Generally, combined treatment includes agents against both viruses, such as lamivudine (3TC). However, HBV resistance to 3TC is high. Adefovir dipivoxil (ADV) has shown its efficacy for treating 3TC-resistant (3TC-R) HBV in HIV-coinfected patients. ADV combined with pegylated interferon (PEG-IFN) has never been evaluated in this population. METHODS: HIV-HBV-coinfected patients with positive HBV e antigen (HBeAg), documented 3TC-R HBV mutation and antiretroviral treatment including 3TC were selected and received ADV (10 mg daily) and PEG-IFN-alpha2a (180 microg weekly) for 48 weeks. RESULTS: Of 18 eligible patients (n=16 [89%] male, mean +/-SD age 40.45 +/-4.82 years), 17 were treated for 48 weeks. One stopped IFN treatment because of adverse events and continued ADV only. The median (interquartile range) HBV DNA at baseline was 8.0 (5.30-8.97) log10 copies/ml and the median (95%/ confidence interval [CI]) decrease after 48 and 72 weeks was 3.6 (4.9-2.4) and 1.4 (-5.0-2.2) log,0 copies/ml, respectively. None of the patients became HBeAg-negative. Median (95%/ CI) decrease of serum alanine aminotransferase was 27.8 (-66.2-10.5) IU/ml after 48 weeks and 93.0 (-80.0-26.1) IU/ml after 72 weeks. CONCLUSIONS: ADV and PEG-IFN is safe and effective for treating 3TC-R HBV in HIV patients. However, on-treatment response was not maintained off therapy and did not lead to HBV seroconversion. The combination had no effect on HIV disease progression.

Efficacy of early treatment of acute hepatitis C infection with pegylated interferon and ribavirin in HIV-infected patients.

BACKGROUND: Treatment of acute hepatitis C (HCV) in HIV-infected patients has been poorly addressed. OBJECTIVE: To evaluate the efficacy and tolerability of a 24 week course of pegylated interferon alfa 2a (PegIFNalpha2a) and ribavirin for the treatment of acute HCV infection in HIV-infected patients. METHODS: This was a prospective pilot study of 25 consecutive HIV-infected men with acute HCV infection defined by documented HCV seroconversion to anti-HCV positive antibody and positive qualitative HCV RNA measurement. Patients with detectable HCV RNA (> 50 IU/ml) 12 weeks after diagnosis were offered treatment with PegIFNalpha2a (180 microg/week) and ribavirin (800 mg/day) for 24 weeks. Sustained virological response was defined by a negative qualitative HCV RNA measurement 24 weeks after the end of treatment. RESULTS: At baseline, 23 patients were taking HAART, 23 patients had HIV RNA < 200 copies/ml and a median CD4 count of 345 cells/microl. Only one patient, with genotype 3 HCV, had a spontaneous clearance of HCV RNA. Of the remaining 24 patients, four refused anti-HCV therapy, ribavirin was contraindicated in one and 19 initiated anti-HCV therapy. Median time between acute HCV diagnosis and initiation of study treatment was 14 weeks. Of the 14 patients who have achieved the post-treatment follow-up at 24 weeks, 10 had a sustained virological response (71%). Study treatment was well tolerated, with no change in CD4 cell count. CONCLUSION: Early treatment of acute HCV infection with PegIFNalpha2a and ribavirin for 24 weeks yields a high sustained virological response rate in HIV-infected patients.

Treatment of acute HCV infection in HIV-positive patients: experience from a multicentre European cohort.

BACKGROUND: Early treatment of acute HCV infection has been shown to improve virological response rates in HIV-positive patients; however, details on when and how to best treat acute HCV infection remain unclear at present. METHODS: In this European multicentre cohort study, HIV-positive patients with acute HCV infection were offered immediate or delayed anti-HCV therapy, pegylated interferon or pegylated interferon plus ribavirin combination therapy for 24 or 48 weeks, depending on the local protocol. The main outcome measure was the rate of sustained virological response (SVR). RESULTS: A total of 150 HIV-infected men with acute HCV were enrolled between 2001 and 2006, 111 of whom received anti-HCV therapy. The predominant HCV genotype was type 1 and was present in 71 (64%) patients. Patients were treated with pegylated interferon (n=14) or pegylated interferon plus ribavirin (n=97), with a median duration of treatment of 25 weeks. SVR was obtained in 62% (95% confidence interval 52-71) of patients. There was no difference in SVR by genotype, CD4(+) T-cell count, HIV RNA, HCV RNA, alanine aminotransferase levels or use of ribavirin. Negative HCV RNA at weeks 4 and 12 were strong predictors of SVR. CONCLUSIONS: High rates of SVR (62%) were obtained in HIV-coinfected patients with acute HCV infection undergoing early anti-HCV treatment using pegylated interferon alone or in combination with ribavirin. Treatment response at weeks 4 and 12 might be of help to further guide treatment duration. Urgent prospective studies are needed to further determine the optimal treatment regimen and the duration of therapy.