Article

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

ABSTRACT

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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    • "EFV is primarily metabolised by the CYP2B6 enzyme and to a lesser extent by CYP3A5, CYP3A4, CYP2A6 and CYP1A2 isoforms of the cytochrome P450 system in the liver [20, 21] . The gene coding for CYP2B6 is highly polymorphic and the CYP2B6 c.516G > T SNPs [11,212223242526272829303132 and CYP2B6 c.983 T > C SNPs [23, 25,3334353637 have been reportedly associated with reduced EFV oral clearance resulting in increased plasma EFV concentrations. The single nucleotide variant CYP2B6 c.516 T is linked to a CYP2B6 mRNA splice variant that lacks exons four to six and consequently lower levels of functional CYP2B6 enzyme [24], while the CYP2B6 c.983C variant causes a non-synonymous amino acid change from isoleucine to threonine at position 328 in exon 7 and, thus, reduced CYP2B6 activity [37] . "
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