By Liz Highleyman

Management of patients coinfected with HIV and hepatitis C virus (HCV) is complicated by potential interactions between drugs used to treat the 2 diseases. Interactions that lower drug levels, for example, can lead to compromised effectiveness.

Most studies have shown that rates of sustained response to interferon-based therapy for hepatitis C are lower in HIV-HCV coinfected compared with HCV monoinfected individuals. An adequate concentration of ribavirin added to pegylated interferon helps prevent HCV relapse after completion of treatment.

As reported at the recent 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008), French researchers compared serum ribavirin levels in 34 coinfected and 64 HCV monoinfected patients receiving the same ribavirin doses. Among the coinfected patients, the median CD4 count was relatively high, 430 cells/mm3, and 5 patients (about 15%) were not taking antiretroviral therapy.

At baseline, the median body mass index (22.6 vs 24.7) was lower for the coinfected compared with the HCV monoinfected patients (P = 0.04); ribavirin is typically dose adjusted based on body weight.

Results

• There was no significant difference in ribavirin intake between HIV-HCV coinfected and HCV monoinfected patients (12.9 vs 13.3 mg/kg; P = 0.24; non-significant).

• However, the median ribavirin concentration was significantly lower in coinfected compared with HCV monoinfected patients (2.5 vs 3.2 mcg/ml; P = 0.005).

• Among coinfected patients, the median ribavirin concentration was significantly lower in patients on antiretroviral therapy compared with those who were not (2.2 vs 4.0 mcg/ml; P = 0.02).

• There was no significant difference in ribavirin concentrations between HCV monoinfected patients and coinfected patients not receiving antiretroviral drugs (P = 0.302; non-significant).

• Ribavirin concentrations were not influenced by fibrosis stage (Metavir F0-F2 vs F3-F4).

• End of treatment (EOT) response rates in the coinfected and HCV monoinfected patients were 52.9% and 64.1%, respectively (P = 0.39; non-significant).

• Sustained virological response (SVR) rates 24 weeks after completion of treatment were 35.3% versus 50.0%, respectively (P = 0.20; non-significant).

• Overall, there was no association between serum ribavirin concentrations and EOT or SVR rates in coinfected or HCV monoinfected patients.

• In the subgroup of patients with HCV genotype 1 or 4, the median ribavirin level was higher in patients who achieved an EOT response (4.2 vs 2.9 mcg/mL; P = 0.08), but there was no significant association with SVR.

"Despite a comparable intake of ribavirin, serum concentration of ribavirin was lower in coinfected patients under [antiretroviral therapy] than in [HCV] monoinfected patients," the researchers concluded.

They suggested that this difference might be explained by a metabolic interaction between antiretroviral drugs and ribavirin.

Although they did not observe any association between ribavirin concentration and response rate in this retrospective study, in which only a small number of HIV positive patients were not receiving antiretroviral therapy, they suggested that the effect might play a role in the lower response rates observed in other studies of HIV-HCV coinfected patients.

Paris Descartes University; APHP, Cochin Hospital, Hepatology; INSERM U.567, Paris, France; Paris Descartes University; APHP, Cochin Hospital, Pharmacology, Paris, France; APHP, Cochin Hospital, Hepatology, Paris, France.

11/25/08

Reference
J Quioc, V Jullien, V Mallet, and others. Antiretrovirals reduce Ribavirin exposure in HIV-HCV coinfected patients. 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008). San Francisco. October 31-November 4, 2008. Abstract 1269.