Short-Term Neuropsychiatric Side Effects: Etravirine vs. Efavirenz

"Efavirenz is a cornerstone of many antiretroviral regimens because of its efficacy, once-daily dosing, and tolerability, but in some patients, it can cause troublesome neuropsychiatric problems. To determine whether etravirine might lead to fewer such problems, researchers conducted a randomized, double-blind, placebo-controlled study among HIV-infected treatment-naive patients. The study was sponsored by the maker of etravirine.

A total of 157 patients received etravirine (dosed at 400 mg once daily) or efavirenz, each together with two nucleosides; 60% received tenofovir/FTC, 26% received abacavir/3TC, and 14% received AZT/3TC. The study population was 81% men and 85% white. Median age was 36; median baseline CD4 count, 302 cells/mm³; and median baseline viral load, 4.8 log copies/mL.

During 12 weeks of treatment, 93% of the efavirenz group and 88% of the etravirine group achieved viral loads <400 copies/mL; median CD4-count increases were 121 and 146 cells/mm³, respectively. Neuropsychiatric adverse reactions occurred in 46% of efavirenz recipients versus 17% of etravirine recipients; serious neuropsychiatric reactions (grades 2–4) occurred in 17% versus 5%. The prevalence of neuropsychiatric problems peaked at week 2 (44% for efavirenz vs. 22% for etravirine), but the difference between groups remained significant at week 12 (30% vs. 12%). The most common nervous system side effect was dizziness, and the most common psychiatric effect involved sleep disorders. Overall, 10 patients discontinued etravirine, and 8 discontinued efavirenz (4 in each group because of skin rash); neuropsychiatric problems contributed to five of the efavirenz discontinuations and one of the etravirine discontinuations.

Comment: The authors state that the lower neuropsychiatric event rate observed with etravirine could lead to better long-term adherence, but the difference in discontinuation rates for the two drugs was modest. Furthermore, the study was relatively short and focused on the period of treatment when adverse effects from efavirenz are generally most troublesome. Drawing long-term conclusions from this study is therefore difficult".

— Keith Henry, MD

Published in Journal Watch HIV/AIDS Clinical Care February 7, 2011

CITATION(S):

Nelson M et al. A comparison of neuropsychiatric adverse events during 12 weeks of treatment with etravirine and efavirenz in a treatment-naive, HIV-1-infected population. AIDS 2011 Jan 28; 25:335.