2NN: efficacy
The 2NN study compared the efficacy and safety of treatment with d4T and 3TC, and NVP once daily (QD), NVP twice daily (BID), EFV or the combination of NVP and EFV in 1216 ARV-naive HIV-1-infected patients at 48 weeks.
The primary endpoint of 2NN was the proportion of patients with treatment failure.
Week 48 data showed no significant differences in treatment failure between regimens: the majority of patients in each arm had VLs <50 copies/mL: 65.4% in the NVP BID arm; 70% in the NVP QD arm; and 70% in the EFV arm.
(van Leth F, et al. Lancet 2004; 636:1250-1253)
2NN efficacy Side Effects
The safety profiles of NVP and EFV differed in the 2NN study and authors advised this to be considered when selecting a treatment regimen.
One of the key findings showed a higher rate of hepatobilary lab toxicity in the NVP once-daily compared to the twice-daily arm (13.2 vs 7.8, p=0.002), despite similar efficacy. The results, presented at the Retrovirus conference in February 2003, provided key comparative data for how NNRTIs have subsequently been used in clinical practice: research into the risk factors for serious rash-associated hepatic toxicity led to regulatory changes in the product labeling, with an indication to only prescribe NVP in treatment naïve patients with CD4 count <250 cells/mm3 in women and <400 cells/mm3 in men.
(image: Storfer, S et al. 10th EACS, Dublin. 2005.Abs PE9.6/2)
At the EACS meeting Dublin, 2005, Stephen Storfer from Boehringer Ingelheim presented an analysis of hepatic events based on Thai and non-Thai patients who started treatment based on these new CD4 guidelines that tied the higher rates seen in the once-daily nevirapine arm to a single site in Thailand.
(image: Storfer, S et al. 10th EACS, Dublin. 2005. Abs PE9.6/2)
2nn Three Years Later
Data collected retrospectively for almost 3 years confirmed no significant differences between the treatment regimens (2007, IAS meeting).
It only followed <50% of the original cohort with some disparities between the groups: 567 patients were followed out to week 144.
During the interim period (week 49-144), there were more failures in the once daily arm (45% vs. 36%) though it didn’t reach statistical significance. It’s not certain if this is reflective of a trend, or simply a regression to the mean. There were slightly more failures in the twice daily arm for weeks 0-48.
F Wit, et al (for the 2NN study group). Three-year extended follow-up of the 2NN study: a randomised comparative trial of first-line antiretroviral therapy with regimens containing either nevirapine, efavirenz or both drugs combined, together with stavudine and lamivudine. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, 2007. Sydney, Australia. Abstract (poster) WEPEB032
Parts of this CME:
start of the CME
Clinical pharmacology of NVP
Pharmacokinetics
Other clinical sudies on NVP QD efficacy
Transition from BID to QD: clinical data
The future
Conclusions