Alicia Gutiérrez-Valencia, PharmD; Pompeyo Viciana, MD, PhD; Rosario Palacios, MD, PhD; Rosa Ruiz-Valderas, MD, PhD; Fernando Lozano, MD, PhD; Alberto Terrón, MD; Antonio Rivero, MD, PhD; Luis F. López-Cortés, MD, PhD; Sociedad Andaluza de Enfermedades Infecciosas
More than 50% of patients who start efavirenz treatment develop limiting neuropsychiatric adverse events (NPAEs).
To assess whether stepwise dosing of efavirenz decreases the incidence and severity of NPAEs while maintaining virologic efficacy.
Randomized, double-blind, controlled trial.
7 HIV clinics in Spain.
114 HIV-infected patients eligible for efavirenz treatment plus 2 nucleoside or nucleotide reverse transcriptase inhibitors.
Random assignment (by computer-generated sequence) to receive efavirenz, 200 mg/d on days 1 through 6, 400 mg/d on days 7 through 13, and 600 mg/d on day 14 and after, or efavirenz, 600 mg/d, from day 1. Both groups received 2 nucleoside or nucleotide reverse transcriptase inhibitors chosen by the patient's physician.
Neuropsychiatric symptoms and sleep quality were assessed by questionnaires at 0, 7, 14, and 30 days. The primary outcome was efavirenz-related NPAEs during the first 2 weeks, and the secondary outcome was plasma HIV RNA level at 24 weeks.
Compared with the stepped-dose group, the full-dose group had higher incidence and severity of dizziness (66.0% vs. 32.8%; PÂ = 0.001), hangover (45.8% vs. 20.7%; PÂ = 0.008), impaired concentration (22.9% vs. 8.9%; PÂ = 0.038), and hallucinations (6.1% vs. 0%; PÂ = 0.056) during the first week. From week 2, the incidence of efavirenz-related NPAEs was similar in both groups, although the severity was greater in the full-dose group. Virologic and immunologic efficacy seemed similar in both groups.
The sample size was calculated on the basis of a high absolute difference in rates of efavirenz-related NPAEs between the groups. A lower absolute difference and a larger sample size could have made the differences between groups reach statistical significance beyond the first week. In addition, the sample size does not allow confirmation of similar efficacy between treatment groups.
Stepwise dose escalation of efavirenz over 2 weeks reduces the incidence and intensity of efavirenz-related NPAEs while maintaining efficacy.
ConsejerÃa de Salud, Junta de AndalucÃa, Spain.
Efavirenz is a powerful component of effective highly active antiretroviral therapy. Unfortunately, about half of patients develop disturbing neuropsychiatric side effects. Although side effects subside for many patients as they continue to take the drug, other patients have to stop taking efavirenz.
This randomized trial compared full-dose efavirenz with stepped-dose efavirenz during the first 2 weeks of treatment and found fewer side effects during the first week in patients receiving stepped-dose therapy. After 24 weeks, HIV RNA levels and CD4+ cell counts were similar in both groups.
The study had too few patients to detect small differences in effectiveness.
FD = full dose; NPAE = neuropsychiatric adverse event; SD = stepped dose.
The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.
Gutiérrez-Valencia A, Viciana P, Palacios R, et al, Sociedad Andaluza de Enfermedades Infecciosas. Stepped-Dose Versus Full-Dose Efavirenz for HIV Infection and Neuropsychiatric Adverse Events: A Randomized Trial. Ann Intern Med. 2009;151:149–156. doi: 10.7326/0003-4819-151-3-200908040-00127
Download citation file:
Published: Ann Intern Med. 2009;151(3):149-156.
HIV, Infectious Disease.
Results provided by:
Copyright © 2019 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
Conditions of Use