Safety and effectiveness of efavirenz versus nevirapine-based regimens in resource-limited settings

Abstract

639–641Keywords: efavirenz, effectiveness, modelling, nevirapine, safety,sub-Saharan AfricaCombination antiretroviral therapy (ART) with eitherefavirenz (EFV) or nevirapine (NVP), both nonnucleo-side reverse transcriptase inhibitors (NNRTIs), and twonucleoside reverse transcriptase inhibitors (NRTI) isrecommended by the WHO as first-line therapy inresource-limited countries [1]. Compared with NVP,EFV is easier to monitor, is relatively well tolerated, hasless frequent and less severe rash and hepatic toxicity thanNVP, and can be administered once daily. Whereas NVPandEFVhavegenerallycomparableclinicalandvirologicefficacy [2–5], because of lower drug–drug interactions,EFV-based ART is associated with superior virologicoutcome compared with NVP-based ART in individualswith tuberculosis (TB) receiving anti-TB therapycontaining rifampicin. Therefore, efavirenz is theNNRTI antiretroviral drug of choice of TB-coinfectedindividuals [6–9]. However, there have been concernsregarding potential for central nervous system birthdefects with first-trimester exposure to EFV based onstudiesinpregnantrhesusmacaquesandretrospectivecasereportsinhumansthathavelimitedEFVuseinwomenofchildbearing age. This is a problem in many resource-limitedsettings,wherewomenconstitute50%or moreofHIV-infected individuals and TB is endemic, but there islimited access to contraception or women may wish tobecome pregnant.In this issue, Ouattara and colleagues use a computersimulation model to evaluate the risks and benefits ofusing EFV and NVP in women of childbearing age inresource-limited countries [10]. Using the previouslyvalidated Cost-Effectiveness of Preventing AIDS Com-plications (CEPAC) International model, the authorssimulated the trade-off between potential excess birthdefects and potential long-term clinical benefits forwomen starting EFV-based versus NVP-based ART inCote d’Ivoire. In a ‘hypothetical’ cohort of 100000women starting ARTwith EFV, the authors found that adrug with lower toxicity and requiring less regimenswitching led to approximately 911 more women aliveafter 10 years compared with those starting with NVP, animprovement in survival of approximately 1%. However,over thesameperiod,therewere59morebirthdefectsinwomen initiating EFV-based ART than those startingwith NVP. The authors concluded that in Cote d’Ivoire,initiating ART with EFV instead of NVP is likely to