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Efavirenz is an important component of many antiretroviral therapy (ART) regimens, but patients often experience severe and debilitating neuropsychiatric adverse events (NPAEs) during the first weeks of treatment. Although firm evidence that these NPAEs are dose related is lacking, investigators in Spain (several of whom have received honoraria and grants from the manufacturer of efavirenz) postulated that initiating efavirenz in a stepwise fashion might diminish NPAEs while maintaining the drug's virologic and immunologic effects.
In a multicenter, randomized, double-blind, clinical trial, 114 patients were started on efavirenz, as part of a standard triple-therapy regimen, at either the standard dose (600 mg/day) or a stepped dose (200 mg/…