Abstract | BACKGROUND: More than 50% of patients who start efavirenz treatment develop limiting neuropsychiatric adverse events (NPAEs). OBJECTIVE: To assess whether stepwise dosing of efavirenz decreases the incidence and severity of NPAEs while maintaining virologic efficacy. DESIGN: Randomized, double-blind, controlled trial. SETTING: 7 HIV clinics in Spain. PATIENTS: INTERVENTION: MEASUREMENTS: 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. RESULTS: Compared with the stepped-dose group, the full-dose group had higher incidence and severity of dizziness (66.0% vs. 32.8%; P = 0.001), hangover (45.8% vs. 20.7%; P = 0.008), impaired concentration (22.9% vs. 8.9%; P = 0.038), and hallucinations (6.1% vs. 0%; P = 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. LIMITATIONS: 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. CONCLUSION: Stepwise dose escalation of efavirenz over 2 weeks reduces the incidence and intensity of efavirenz-related NPAEs while maintaining efficacy. PRIMARY FUNDING SOURCE: Consejería de Salud, Junta de Andalucía, Spain.
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Authors | Alicia Gutiérrez-Valencia, Pompeyo Viciana, Rosario Palacios, Rosa Ruiz-Valderas, Fernando Lozano, Alberto Terrón, Antonio Rivero, Luis F López-Cortés, Sociedad Andaluza de Enfermedades Infecciosas |
Journal | Annals of internal medicine
(Ann Intern Med)
Vol. 151
Issue 3
Pg. 149-56
(Aug 04 2009)
ISSN: 1539-3704 [Electronic] United States |
PMID | 19581631
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Alkynes
- Anti-HIV Agents
- Benzoxazines
- Cyclopropanes
- Reverse Transcriptase Inhibitors
- efavirenz
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Topics |
- Adult
- Aged
- Alkynes
- Anti-HIV Agents
(administration & dosage, adverse effects, blood)
- Benzoxazines
(administration & dosage, adverse effects, blood)
- CD4 Lymphocyte Count
- Cyclopropanes
- Double-Blind Method
- Drug Administration Schedule
- Female
- HIV Infections
(drug therapy, immunology, virology)
- Humans
- Male
- Mental Disorders
(chemically induced)
- Middle Aged
- Reverse Transcriptase Inhibitors
(administration & dosage, adverse effects, blood)
- Sample Size
- Sleep Wake Disorders
(chemically induced)
- Viral Load
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