Background:  Nevirapine (NVP) is registered for use with a dosage of 200 mg twice daily. With the availability of once-daily nucleosides, NVP is often prescribed once daily in clinical practice. Some studies raised concern regarding lower NVP once-daily efficacy. We performed a collaborative cohort analysis to investigate the relationship between NVP dosing schedule and treatment efficacy.

Methods:  Patients in the Dutch ATHENA and Swiss SHCS cohorts who had used NVP-based combination therapy were included. We describe the percentage of patients on twice-daily and once-daily NVP who reached HIV RNA levels below the limits of detection of 50 copies/mL. Time to below the limits of detection, and time to loss of virological response was performed using Kaplan-Meier survival analysis. Comparison of change in CD4 count between NVP twice-daily and once-daily dosing was compared by non parametric Wilcoxon test.

Results:  We included 5244 patients on a NVP-containing regimen, 4471 on twice-daily and 629 on once-daily regimens. We analyzed 3 groups with available viral load and CD4 count:  naive patients (n = 853), pre-treated patients starting NVP with undetectable HIV RNA (n = 1700), and pre-treated with detectable HIV RNA (n = 2054). Among naives, 82% of those on a twice-daily regimen (n = 771) reached HIV RNA below the limits of detection at 2 years, in comparison with 84% of those starting a once-daily regimen (n = 82, p = 0.67). Naive patients on NVP once-daily took longer to become undetectable than patients on a twice-daily regimen (log rank 0.04). In pre-treated patients with HIV RNA below limits of detection, we observed no difference in time to loss of virological response between NVP prescribed twice daily or once daily (n = 1507 and 193, respectively) until week 96 (log rank 0.084). In pre-treated patients with detectable HIV RNA, NVP once daily (n = 1792) was associated with better virological outcome at week 96 compared to patients on twice daily (n = 262) dosing schedule (50% vs 69%, p <0.0001). In pre-treated patients with a detectable RNA, time to viral load suppression was significantly shorter in patients on a once-daily regimen (log rank 0.001). In the latter population, CD4 cell count increase at 2 years was significantly better in the NVP once-daily group (+80 vs +110 cells/mm³, p = 0.0009).

Conclusions:  These data suggest that NVP once daily in clinical practice is at least as efficient as NVP prescribed twice daily. For patients with detectable HIV RNA who have been exposed to other antiretroviral drugs and commencing a regimen including NVP, NVP once daily is associated with better and faster virological suppression, as well as a stronger immune restoration.