Coinfection

Adequate Ribavirin Level Promotes Sustained Response to Interferon-based Therapy for HIV-HCV Coinfected Patients

Ribavirin plays an important role in preventing relapse after completion of interferon-based therapy for chronic hepatitis C. But this treatment does not work as well in HIV/HCV coinfected people, and the effects of ribavirin in this group are not fully understood.

In previous studies, researchers have found a relationship between ribavirin plasma concentrations and risk of virological failure of therapy. Two poster presentations at the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) last week in Montreal shed more light on the drug's impact.

Study 1

In the first study, Judit Morello and colleagues from Hospital Carlos III in Madrid, Spain prospectively followed 160 interferon treatment-naive HIV/HCV confected patients starting pegylated interferon alfa-2a (Pegasys) or alfa-2b (PegIntron) at standard doses plus weight-adjusted ribavirin (approximately 13 mg/kg/day) for 48 weeks.

Most participants (68%) were men, nearly all were Caucasian, and the median age was 42 years. Just over 80% were on HAART, but none had previously been treated for hepatitis C. At baseline, 60% had hard-to-treat HCV genotypes 1 or 4, the mean serum HCV RNA level was about 6 log IU/mL, and 16% had advanced liver fibrosis or cirrhosis (Metavir F3-F4).

The researchers assessed virological response at different time points using an assay with a limit of detection of 10 IU/mL.


Results

  • Ribavirin trough level < 2.5 mcg/mL at week 4 (odds ratio [OR] 4.5);
  • Baseline serum HCV RNA (OR 2.5 per log IU/mL);
  • HCV genotypes 1 or 4 (OR 13.3).

Based on these findings, the investigators concluded, "Monitoring of ribavirin plasma concentrations at week 4 may permit early prediction of HCV relapse, allowing consideration of early interventions, such as increasing ribavirin doses or prolonging the length of HCV therapy in difficult-to-treat HIV-HCV coinfected patients."

Study 2

In a related study, Cristina Tural and colleagues analyzed the association between ribavirin plasma trough concentrations and HCV RNA clearance in the Spanish CORAL-2 study.

The study included 65 interferon-naive HIV-HCV coinfected patients. About 72% were men, the mean age was 41 years, and about 80% had HCV genotype 1. They had well-controlled HIV disease, with a mean CD4 count of roughly 600 cells/mm3 and 75% with undetectable HIV viral load.

Participants were randomly assigned to receive standard therapy with 180 mcg/week Pegasys plus 1000-1200 mg/day ribavirin for 48 weeks, or else start with larger induction doses of both Pegasys (270 mcg/week) and ribavirin (1600 mg/day, given with erythropoietin to manage anemia) for 4 weeks, followed by standard doses for an additional 44 weeks.


Results

"The relationship between EVR and ribavirin plasma trough concentrations suggests that [patients with] difficult-to-treat HCV genotypes could benefit from higher doses of ribavirin," at least during the first weeks of treatment, the researchers concluded.

2/20/09

References

J Morello, S Rodríguez-Nóvoa, P Barreiro, and others. Ribavirin Plasma Levels at Week 4 Predicts Hepatitis C Virus Relapse in HIV/HCV-co-infected Patients Treated for Hepatitis C. 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009). Montreal, Canada. February 8-11, 2009. Abstract 842.

C Tural, J Moltó, R Solá, and CORAL-2 Study Group. Effect of Ribavirin Plasma Trough Concentrations on Virological Response in Co-infected Patients on 4-Week Induction Dose of Ribavirin (1600 mg/day) and Peg-interferona-2a (270 mg/week): Results from the CORAL-2 Study. 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009). Montreal, Canada. February 8-11, 2009. Abstract 841.