Other clinical studies on NVP QD efficacy
The DAUFIN study
The DAUFIN study compared AZT/3TC 300 mg/150 mg plus NVP 200 mg twice daily with 3TC 300 mg, TDF 245 mg and NVP 400 mg once daily.
The study was stopped after early virological failure was observed in 8/36 (22.2%) once-daily patients.
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.
(Clotet B. Once-daily dosing of nevirapine in HAART.J Antimicrob Chemother. 2008 Jan;61(1):13-6)
ATHENA & Swiss HIV Cohort Study
Analysis of 5,244 patients, including 4,471 patients receiving twice-daily NVP and 629 patients receiving once-daily NVP. They also looked at treatment responses to once- and twice-daily Viramune using three main study characteristics:
1. those who used either dose upon starting HIV treatment for the first time,
2. those who switched to either dose after achieving an undetectable viral load with other antiretrovirals,
3. treatment-experienced patients with detectable viral loads who switched to either dose of NVP.
Among those starting treatment for the first time with a NVP regimen, 84% of the 82 patients on once-daily NVP and 84% of the 771 patients on twice-daily NVP had undetectable viral loads—below 50 copies—after two years of treatment, and it took longer for viral loads to go undetectable using once-daily NVP.
Among those who switched to NVP with an undetectable viral load, virologic responses were durable and comparable among the 1,507 using twice-daily NVP and the 193 patients using once-daily NVP for up to 96 weeks of follow-up.
Pretreated patients with detectable viral loads had better virologic outcomes with the use of once-daily, compared with twice-daily NVP. Time to viral load suppression was also shorter using once-daily NVP in this population of patients, and gains in CD4 cell counts were significantly better in the once-daily NVP group (an increase of 110 cells versus 80 cells in the twice-daily group).
“These data,” Dr. Calmy and her fellow authors suggest in the published study abstract, “suggest that once-daily NVP in clinical practice is at least as efficient as NVP prescribed twice a day. For patients with detectable [viral loads] who have been exposed to other antiretroviral drugs and [are] commencing a regimen including NVP, NVP once daily is associated with better and faster virologic suppression, as well as stronger immune restoration.”
(A. Calmy,et al. Nevirapine Administered Once Daily Is as Efficient as a Twice-daily Dosing. CROI,2008)
Parts of this CME:
start of the CME
Clinical pharmacology of NVP
Pharmacokinetics
2NN: efficacy
Transition from BID to QD: clinical data
The future
Conclusions