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.
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Gutiérrez-Valencia A, Viciana P, Palacios R, Ruiz-Valderas R, Lozano F, Terrón A, et al. 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
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Published: Ann Intern Med. 2009;151(3):149-156.
HIV, Infectious Disease.
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