NRTIs Interferons

Interferon alfa does not alter the pharmacokinetics of didanosine or lamivudine to a clinically relevant extent. Interferon alfa and, particularly, interferon beta can cause an increase in the serum levels of zidovudine. HIV-positive patients infected with hepatitis C and treated with interferon alfa and ribavirin may be at special risk of NRTI-associated lactic acidosis. Interleukin-2 appears not to interact significantly with zidovudine. 

The use of ribavirin with the NRTIs may result in increased toxicity (lactic acidosis, blood dyscrasias and hepatotoxicity), which may be more frequent with didanosine than other NRTIs. These effects may also be exacerbated by the additional use of interferon for hepatitis C. Early in vitro data su ested that ribavirin may reduce the antiretroviral effects of some NRTIs but this does not appear to have been demonstrated in practice. 

In vitro, ribavirin reduced the intracellular activation and antiretroviral activity of lamivudine. However, in a study in 22 HIV-positive patients with hepatitis C, ribavirin 800 mg daily had no statistically significant effect on the pharmacokinetics of lamivudine (a 27% increase in AUC), and no effect on the intracellular activation of lamivudine, when compared with 24 similar patients who received placebo. As with all NRTIs, lamivudine has, rarely, been associated with lactic acidosis, and the UK manufacturers of all NRTIs state that patients co-infected with hepatitis C and treated with interferon alfa and ribavirin may be at increased risk of lactic acidosis. Patients at increased risk should be monitored closely. ... 

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