Once-daily dosing of nevirapine in HAART

Abstract

Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens provide simpler and more easily tolerated treatment alternatives to protease inhibitor-based regimens, potentially improving adherence. Long-term viral suppression relies on adherence to a prescribed antiretroviral treatment regimen. Simplification of dosing schedules has prompted investigations into once-daily dosing regimens; nevirapine once-daily dosing strategies are currently under investigation. The DAUFIN study compared zidovudine/lamivudine 300 mg/150 mg plus nevirapine 200 mg twice daily with lamivudine 300 mg, tenofovir 245 mg and nevirapine 400 mg once daily. The study was stopped after early virological failure was observed in 8/36 (22.2%) once-daily patients. Baseline characteristics in once-daily patients with and without virological failure indicated significantly higher median plasma viral load and significantly lower median CD4+ cell counts. Presented nevirapine plasma trough levels were not stratified by virological failure or success. Resistance mutations accumulated while on treatment; high rates of K65R mutations and severe NNRTI resistance profiles might be indicative of ongoing viral replication caused by suboptimal nevirapine plasma trough concentrations under non-adherence to the treatment regimen. Non-B-subtype infection (subtype A or C not stated) was observed in 4/10 patients with virological failure. The DAUFIN study was prematurely stopped without predetermined cessation criteria, presented data are not complete, and results should be interpreted with caution. Nevirapine pharmacokinetics make it suitable for once-daily dosing. However, due to rash and concerns over liver toxicity, nevirapine once daily might best be administered in patients with undetectable viral load after initial treatment with nevirapine twice daily. The NODy study will evaluate the efficacy and safety of switching to nevirapine once daily compared with remaining on twice-daily treatment.