It is widely accepted that non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral regimens provide simpler and more easily tolerated treatment alternatives compared with protease inhibitor (PI)-based regimens, potentially leading to improved adherence.

Long-term HIV suppression relies on adherence to a prescribed antiretroviral regimen. The desire for simplified dosing schedules has prompted investigations into once-daily regimens. Once-daily dosing strategies using nevirapine (Viramune) are currently under investigation.

The DAUFIN study compared 300/150 mg AZT/3TC (Combivir) plus 200 mg nevirapine twice daily versus 300 mg 3TC (lamivudine; Epivir), 245 mg tenofovir (Viread), and 400 mg nevirapine once daily.

The study was stopped after early virological failure was observed in 8 of 36 patients (22.2%) taking the once-daily regimen. Baseline characteristics of once-daily patients with and without virological failure indicated significantly higher median plasma viral load and significantly lower median CD4 cell counts. Also, non-B subtype HIV infection (whether with subtype A or C was not stated) was observed in 4 of 10 patients (40%) with virological failure.

In this study, nevirapine plasma trough levels were not stratified by virological failure or success, to determine whether poorer outcomes were associated with low drug concentrations in the once-daily arm.

HIV mutations conferring drug resistance accumulated while on treatment. High rates of the K65R mutation and severe NNRTI resistance profiles might be indicative of ongoing viral replication due to suboptimal nevirapine plasma trough concentrations among patients who were non-adherent to the treatment regimen, the researchers suggested.

Since the DAUFIN study was prematurely stopped without predetermined cessation criteria, the data presented are not complete, and therefore results should be interpreted with caution.

In conclusion, wrote study author Bonaventura Clotet, MD, “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, he added, “will evaluate the efficacy and safety of switching to nevirapine once daily compared with remaining on twice-daily treatment.”

Hospital Universitari Germans Trias i Pujol and IrsiCaixa Foundation, Barcelona, Spain.

12/11/07

Reference
B Clotet. Once-daily dosing of nevirapine in HAART. Journal of Antimicrobial Chemotherapy. November 14, 2007 [Epub ahead of print].