Long-Term Impact of Efavirenz on Neuropsychological Performance and Symptoms in HIV-Infected Individuals (ACTG 5097s)

Washington University School of Medicine, St. Louis, MO 63110, USA.
HIV Clinical Trials (Impact Factor: 2.63). 11/2009; 10(6):343-55. DOI: 10.1310/hct1006-343
Source: PubMed


Efavirenz (EFV) is an antiretroviral (ARV) drug associated with neuropsychological effects. Limited data describing the long-term impact of EFV-based regimens on neuropsychological performance over more than 3 years are available.
We enrolled a subset of participants from a large initially EFV placebo-controlled trial of therapies for HIV subjects naïve to ARV treatment (A5095). Clinical follow-up continued for 184 weeks of study. Subjects were assessed with brief neuropsychological testing, a symptom questionnaire of EFV-associated symptoms, the Pittsburgh Sleep Index, Center for Epidemiologic Studies-Depression Scale, and an anxiety rating interview.
Over 184 weeks on EFV, the median NPZ3 score in 86 evaluable patients improved from baseline by +0.5 (p < .01); all components improved, although higher EFV levels were associated with slightly lower responses. Overall symptom scores did not change, while EFV-associated CNS symptoms increased (p = .01). Median change of bad dream sleep scores and anxiety increased from the baseline while global depression score decreased.
In participants who continued EFV-based regimens, neuropsychological performance improvement from baseline was maintained over 3 years. EFV-based treatment was generally well tolerated, but small increases from baseline in EFV-associated symptoms, bad dreams, and anxiety were detected.

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Available from: David B Clifford, Feb 03, 2014
    • "While the acute CNS side effects of EFV are well recognized , one long-term randomized study found that EFV had no chronic adverse effects on the CNS although these findings may have been impacted by subject drop-out. (Clifford et al. 2009). In our analysis, EFV use was associated with worse NC functioning, specifically in participants without HCV coinfection , with a mean duration of use approximately 1.5 years. "
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    • "Recently, investigators more specifically identified damage to neuronal dendrites by metabolites of efavirenz at concentrations readily detected in CSF of patients receiving efavirenz containing regimens [92]. However, a long-term study of subjects followed for 3 years on efavirenz containing regimens showed stability of neuropsychological testing performance in subjects with normal testing at baseline, suggesting if tolerated, efavirenz does not appear to lead to accumulated neurotoxicity which is clinically detectable [94]. Importantly, the ease of consistently adhering to efavirenz-containing regimens in terms of convenience of dosing must be weighed against potential neurotoxicity in terms of cost-benefit to the CNS. "
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