Efavirenz associated with cognitive disorders in otherwise asymptomatic HIV-infected patients

Neurology. 2011 Apr 19;76(16):1403-9. doi: 10.1212/WNL.0b013e31821670fb.


Background: Despite the availability of potent antiretroviral regimens (combination antiretroviral therapy [cART]), HIV-associated neurocognitive disorders (HAND) are increasingly recognized. Our aim was to investigate the prevalence and treatment-related correlates of HAND, exploring the potential neurotoxicity of antiretrovirals on cognitive functions.

Methods: We performed a cross-sectional single cohort study by consecutively enrolling asymptomatic HIV+ subjects during routine outpatient visits. Each patient was submitted to a comprehensive neuropsychological battery and was considered cognitively impaired on the basis of results obtained in matched healthy HIV-negative subjects. CNS penetration effectiveness (CPE) rank was calculated for cART regimens according to 2010 CHARTER criteria. Factors associated with cognitive impairment were investigated by linear or logistic regression analysis.

Results: A total of 146 patients were enrolled. Of these, 129 (88.4%) were on cART and 59.6% of them were on current regimen from ≥1 year. Sixty-nine patients (47%) were classified as cognitively impaired (35.6% asymptomatic and 11.6% mild neurocognitive impairment). In the multivariate analysis, efavirenz use (odds ratio [OR] = 4.00; p = 0.008) and non-Italian nationality (OR = 3.46; p = 0.035) were associated with increased risk of cognitive impairment, whereas higher education was associated with a lower risk (OR = 0.85; p = 0.002). Furthermore, efavirenz use and age ≥65 years independently predicted worse performance on the double barrage and the Stroop test (time). No association between CPE rank and cognitive impairment was observed.

Conclusions: A high prevalence of HAND was observed in apparently asymptomatic HIV+ individuals. HAND was associated with efavirenz use, suggesting the potential neurotoxicity of this drug. Routine neuropsychological examinations could help clinicians make correct diagnoses and manage mild, but clinically relevant, forms of HAND.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Adult
  • Alkynes
  • Anti-HIV Agents / adverse effects*
  • Antiretroviral Therapy, Highly Active / methods
  • Benzoxazines / adverse effects*
  • Case-Control Studies
  • Chi-Square Distribution
  • Cognition Disorders / chemically induced*
  • Cognition Disorders / epidemiology
  • Cognition Disorders / etiology*
  • Cohort Studies
  • Cyclopropanes
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology
  • Humans
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Neuropsychological Tests
  • Retrospective Studies
  • Young Adult


  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • efavirenz