Pegylated interferon α-2b plus ribavirin for the treatment of chronic hepatitis C in HIV-coinfected patients

https://doi.org/10.1016/j.jinf.2005.09.007Get rights and content

Summary

Objectives

HIV-coinfection accelerates the course of HCV-related liver disease. Since, highly active anti-retroviral therapy significantly improved survival of HIV-patients more coinfected patients develop end stage liver disease. Therefore, treatment options for chronic hepatitis C in HIV-coinfected patients need to be evaluated.

Methods

Efficacy and safety of pegylated interferon α-2b (peg IFN) plus ribavirin (RBV) was examined within this prospective, uncontrolled, multicentre trial. Patients received peg IFN (1.5 μg/kg) once weekly plus RBV 800 mg daily for 48 weeks for HCV genotypes (GT) 1/4 and 24 weeks for GT 2/3.

Results

One hundred and twenty-two patients were enrolled. Patients were predominantly male (68%) and former i.v. drug users (61%). Baseline characteristics (median) were as follows: age 39 years (range 23–58), CD4 count 494 cells/μl (range 150–1578/μl), HIV-RNA 2.3 log copies/ml (range <1.7–5.4 log copies/ml). 61% currently received anti-retroviral treatment. Fifty-six percent had HCV GT 1. EOT response was achieved by 52%. However, only 25% achieved sustained response (SR) due to a high relapse rate. SR rates were significantly higher among patients with GT 2/3 compared to those with GT 1/4 (44 vs. 18%). SR was observed in only one patient without early response (ER). Discontinuation rate was 30%, 21% discontinued due to adverse events.

Conclusion

Peg IFN/RBV appears safe and effective in HIV/HCV-coinfected patients. GT 2/3 is associated with better SR. Lack of ER strongly predicts non-response. High relapse rates substantially reduce treatment success. In terms of toxicity neuro-psychiatric side effects frequently required treatment discontinuation.

Introduction

As human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share routes of transmission concomitant infections with both viruses are common. Coinfection is most prevalent in patients with blood-borne infection.1 However, the risk of sexual transmission of HCV, though generally low, appears to be increased in case of concomitant HIV-infection.2 With regard to geographically different distribution of risk factors for transmission of HIV prevalence of HIV/HCV-coinfection also differs widely. Overall the rate of HCV-coinfection in HIV-infected individuals in Europe is 34%.3 However, in southern and eastern Europe, where i.v. drug use (IVDU) is the predominant route of transmission coinfection rate is as high as 45–48%, whereas in northern and central Europe coinfection shows a prevalence of 23–25%.3

It has been shown repeatedly that the course of hepatitis C-related liver disease is accelerated in HIV/HCV-coinfection. Progression to liver cirrhosis is faster compared to HCV-monoinfected patients4, 5 and patients develop hepatocellular carcinoma at younger age.6 Patients with HIV/HCV-coinfection show a higher risk for progression to advanced fibrosis5, 7 and to end stage liver disease, especially when immunodeficiency progresses.8

As highly active anti-retroviral therapy (HAART) has reduced HIV-related morbidity and mortality, chronic hepatitis has become a major cause for hospitalization and death in coinfected patients. The contribution of HCV related mortality to the overall mortality has increased from 1.5% in 1995 to 14.3% in 2001 in a large French cohort study.9 Therefore, evaluating treatment options for HCV-infection in HIV-coinfected appears particularly important. Under treatment with interferon α (IFN) plus ribavirin (RBV) sustained response (SR) rates of 13–26% were achieved in HIV/HCV-coinfected patients10, 11, 12 compared to about 40% in historical HCV-monoinfected cohorts.13, 14 Discontinuation rates due to adverse events of up to 39%10 generally exceeded those in HCV-monoinfected patients with approx. 10–20%.13, 14 Introduction of pegylated IFN α (peg IFN) has lead to improved SR rates of up to 54–56% in HCV-monoinfected patients as compared to 44–47% under conventional IFN α.15, 16 We evaluated efficacy and safety of peg IFN α-2b plus RBV in HIV/HCV-coinfected patients within a multicentre trial in Germany.

Section snippets

Patients and methods

We performed an open, uncontrolled trial involving 24 German sites. The study was conducted in agreement with the Helsinki declaration on good clinical practice and was approved by local ethics committees. All patients gave written and informed consent prior to enrollment.

Eligible subjects had to have documented chronic HIV-infection and chronic hepatitis C confirmed by positive HCV PCR at least 6 months prior to study entry and fulfill following criteria: older than 18 years, willing to

Response rates

An early treatment response (ER) defined as undetectable HCV RNA at week 12 of treatment was observed in 56/122 patients (46%). At EOT (week 24 for genotypes 2/3, week 48 for genotypes 1/4) overall 63/122 patients (52%) showed negative HCV-RNA. An EOT response was observed in 41% (32/78) of patients with genotypes 1/4 and in 72% (28/39) of patients with genotypes 2/3, respectively. SR rate defined as negative HCV RNA at week 24 of follow-up was 25% (31/122) in all patients. SR rate was 18%

Discussion

Introduction of peg IFN has increased response rates in patients with chronic hepatitis C. Administering peg IFN α-2b plus RBV to HIV/HCV-coinfected patients we observed an overall SR rate of 25%. Actual SR rate might have been underestimated as a substantial number of patients (nine) with EOT response unfortunately was lost for follow-up and therefore counted for as non-responders in the ITT analysis. However, 25% SR appears very much comparable to SR rates in other trials examining peg

Acknowledgements

The study was implemented by the KAAD AIDS Clinicians Collaboration Germany. The authors thank all coworkers of the KAAD study group for their persevering contribution.

This work was supported by an unrestricted grant by Essex Pharma GmbH.

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