Hepatic safety and lack of antiretroviral interactions with buprenorphine/naloxone in HIV-infected opioid-dependent patients.

Background: The safety of buprenorphine/naloxone (bup/nx) in HIV-infected patients has not been established. Prior reports raise concern about hepatotoxicity and interactions with atazanavir. Methods: We conducted a prospective cohort study of 303 opioid-dependent HIV-infected patients initiating bup/nx treatment. We assessed changes in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) over time. We compared bup/nx doses in patients receiving the antiretroviral atazanavir to those not receiving atazanavir. We conducted surveillance for pharmacodynamic interactions. Results: Median AST [37.0 vs. 37.0 units/liter (U/L) respective interquartile ranges (IQRs) 26-53 and 26-59] and ALT (33.0 vs. 33.0 U/L, respective IQRs 19-50 and 18-50) values did not change over time among 141 patients comparing pre-bup/nx exposure with post-bup/nx exposure measures. During bup/nx exposure, 207 subjects demonstrated no significant change in median AST (36.0 vs. 35.0 U/L, respective IQRs 25-57 and 25-61) and ALT (29.0 vs. 31.0 U/L, respective IQRs 19-50 and 18-50) values collected a median of 6 months apart. Analyses restricted to patients with hepatitis C and HIV co-infection yielded similar results, except a small but significant decrease in first to last AST, during treatment with bup/nx (P = 0.048). Mean bup/nx dose, ranging 16.0-17.8 mg, did not differ over time or with co-administration of atazanavir. No pharmacodynamic interactions were noted. Conclusions: Buprenorphine/naloxone did not produce measurable hepatic toxicity or pharmacodynamic interaction with atazanavir in HIV-infected opioid-dependent patients.