Conclusions

• Once-daily nevirapine dosing results in lower Cmin levels compared with twice-daily treatment. However, these pharmacokinetic studies support once-daily dosing assuming that optimal adherence is maintained.

• Several clinical studies in antiretroviral-naïve HIV-1-infected patients suggest a similar virological and immunological response to nevirapine in a dose of 400 mg QD vs 200 mg BID. The frequency of hepatic abnormalities with once-daily nevirapine is dependent on gender, CD4 count and perhaps race.
  Severe rash was more common with once-daily dosing in the 2NN study. Although not observed in other nonrandomized studies of once-daily nevirapine, this and liver concerns remain significant obstacles to routine use of this dosing strategy.

• When compared with NVP BID dosing, antiretroviral regimens in which NVP is dosed at 400 mg once-daily immediately after a 2-week lead-in period are associated with an increased risk of rash leading to treatment interruption or discontinuation. The risk of liver complications is another lingering concern. The pathophysiology of this increased adverse event rate is not fully understood. Although the increased Cmax with NVP QD has been proposed, little evidence to corroborate this can be found within published pharmacokinetic analyses. Risk factors other than high NVP exposure including sex, baseline CD4 count, hepatitis coinfection, race, and genetic profile appear to be important predictors of adverse events associated with nevirapine therapy.

• Once-daily NVP dosing may still have a future. Results from clinical studies suggest that tolerance to high NVP concentrations may develop when a dose-escalation approach is used during the first weeks of therapy. It is theoretically possible that the benefits of QD dosing can be achieved without excess toxicity by switching to NVP QD only after several months of BID administration.
  Moreover Boehringer-Ingelheim is recruiting people for an international study of an extended-release, once-daily formulation NVP.

In conclusion, NVP is currently used twice a day, but the pharmacokinetics and now clinical trial data could indicate that QD dosing is possible and patients could be switched safely once the viral load has been suppressed. That would be anyway problematic in settings where there is no access to viral load.

Cooper CL, van Heeswijk RP. Once-daily nevirapine dosing: a pharmacokinetics, efficacy and safety review. HIV Med. 2007 Jan;8(1):1-7, also available in Medscape (registration free)

Acknowledgments:
special thank to Dr. Moses Bateganya (University of Washington), Dr. Jadunauth B. Raghunauth (National Care and Treatment Centre, Guyana) and Dr. Thomas Minior (FXB Georgetown, Guyana) for taking care of the discussion on the Telemedicine discussion forum, MSF-B for raising the question and Boehringer Ingelheim for providing some of the clinical data.

back to the start

Parts of this CME:
start of the CME
Clinical pharmacology of NVP
Pharmacokinetics
2NN: efficacy
Other clinical sudies on NVP QD efficacy
Transition from BID to QD: clinical data
The future
Conclusions