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Objectives: Once-daily (qd) antiretroviral therapies improve convenience and adherence. If found to be effective, nevirapine extended release (NVP XR) will confer this benefit. The TRANxITION trial examined the efficacy and safety of switching virologically suppressed patients from NVP immediate release (NVP IR) 200 mg twice daily to NVP XR 400 mg qd., Methods: An open-label, parallel-group, noninferiority, randomized (2:1 NVP XR:NVP IR) study was performed. Adult HIV-1-infected patients receiving NVP IR plus a fixed-dose nucleoside reverse transcriptase inhibitor (NRTI) combination of lamivudine (3TC)/abacavir (ABC), tenofovir (TDF)/emtricitabine (FTC) or 3TC/zidovudine (ZDV) with undetectable viral load (VL) were enrolled in the study. The primary endpoint was continued virological suppression with VL < 50 HIV-1 RNA copies/mL up to week 24 (calculated using a time to loss of virological response algorithm). Cochran's statistic (background regimen adjusted) was used to test noninferiority. Adverse events (AEs) were recorded., Results: Among 443 randomized patients, continued virological suppression was observed in 93.6% (276 of 295) of NVP XR- and 92.6% (137 of 148) of NVP IR-treated patients, an observed difference of 1% [95% confidence interval (CI) -4.3, 6.0] at 24 weeks of follow-up. Noninferiority (adjusted margin of -10%) of NVP XR to NVP IR was robust and further supported by SNAPSHOT analysis. Division of Acquired Immunodeficiency Syndrome (DAIDS) grade 3 and 4 events were similar for the NVP XR and NVP IR groups (3.7 vs. 4.1%, respectively), although overall AEs were higher in the NVP XR group (75.6 vs. 60.1% for the NVP-IR group)., Conclusions: NVP XR administered once daily resulted in continued virological suppression at week 24 that was noninferior to that provided by NVP IR, with similar rates of moderate and severe AEs. The higher frequency of overall AEs with NVP XR may be a consequence of the open-label design., (© 2011 British HIV Association.)

Methadone is metabolized by various isoforms of the cytochrome P450 family, which can be induced by many drugs, including nevirapine. The objective of the present study was to determine the effects of coadministration of nevirapine and methadone on the dose-adjusted areas under the concentration-time curves (AUCs) of racemic and (R)-methadone. Twenty-five human immunodeficiency virus-infected subjects taking stable single daily doses of racemic methadone or (R)-methadone were included in this prospective, single-crossover trial. At the baseline, nevirapine was either started as part of a new regimen containing two nucleoside reverse transcriptase inhibitors (NRTIs) or added to an ongoing NRTI regimen. Patients could increase their methadone doses if withdrawal symptoms developed. Twelve-hour pharmacokinetic profiles were obtained before and 28 days after the start of nevirapine treatment. The total concentrations of methadone and its inactive metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), in serum were determined by liquid chromatography-tandem mass spectrometry. Among the 20 evaluable patients, coadministration of nevirapine significantly decreased the mean dose-adjusted AUC of methadone by 41%. AUC reductions were similar for patients taking racemic methadone (37%; n = 11) and (R)-methadone (44%; n = 9). AUC changes ranged from mild increases in three patients to decreases of up to 70%. Fourteen of 20 patients required additional methadone due to withdrawal symptoms. However, the median dose increase was only 15%, which was less than that which would have been expected from the pharmacokinetic data. The AUC of EDDP increased significantly, by 35%. Methadone dose adjustments are justified when methadone is coadministered with nevirapine. Due to extensive variability, the adjustments must be tailored to the individual patient's needs.

7-11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK [ABSTRACT FROM AUTHOR]