Efavirenz and the CNS: what we already know and questions that need to be answered

Antiretroviral therapy reduces neurodegeneration in HIV infection

(2015) Alex K. Bryant et al.   AIDS

Could antiretroviral neurotoxicity play a role in the pathogenesis of cognitive impairment in treated HIV disease?

(2015) Jonathan Underwood et al.   AIDS

Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation

(2014) Viktor Dahl et al.   AIDS

Rilpivirine Versus Efavirenz with Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-Naïve HIV-1–Infected Patients with HIV-1 RNA ≤100,000 Copies/mL: Week 96 Pooled ECHO/THRIVE Subanalysis

(2014) Georg Behrens et al.   AIDS PATIENT CARE AND STDS

Association Between Efavirenz as Initial Therapy for HIV-1 Infection and Increased Risk for Suicidal Ideation or Attempted or Completed Suicide

(2014) Katie R. Mollan et al.   ANNALS OF INTERNAL MEDICINE

Cerebrospinal Fluid Inhibitory Quotients of Antiretroviral Drugs in HIV-Infected Patients Are Associated With Compartmental Viral Control

(2014) Andrea Calcagno et al.   CLINICAL INFECTIOUS DISEASES

Editorial Commentary: Cerebrospinal Fluid Inhibitory Quotients of Antiretroviral Drugs

(2014) C. V. Fletcher   CLINICAL INFECTIOUS DISEASES

Cerebrospinal Fluid Exposure of Efavirenz and Its Major Metabolites When Dosed at 400 mg and 600 mg Once Daily: A Randomized Controlled Trial

(2014) Alan Winston et al.   CLINICAL INFECTIOUS DISEASES

Antiretroviral Treatment of Adult HIV Infection

(2014) Huldrych F. Günthard et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Lack of mitochondrial toxicity of darunavir, raltegravir and rilpivirine in neurons and hepatocytes: a comparison with efavirenz

(2014) A. Blas-Garcia et al.   JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY

Involvement of Nitric Oxide in the Mitochondrial Action of Efavirenz: A Differential Effect on Neurons and Glial Cells

(2014) Nadezda Apostolova et al.   JOURNAL OF INFECTIOUS DISEASES

Neuronal Bioenergetics and Acute Mitochondrial Dysfunction: A Clue to Understanding the Central Nervous System Side Effects of Efavirenz

(2014) Haryes A. Funes et al.   JOURNAL OF INFECTIOUS DISEASES

Efficacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial

(2014)   LANCET

Switching to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of non-nucleoside reverse transcriptase inhibitor with emtricitabine and tenofovir in virologically suppressed adults with HIV (STRATEGY-NNRTI): 48 week results of a randomised, open-label, phase 3b non-inferiority trial

(2014) Anton Pozniak et al.   LANCET INFECTIOUS DISEASES

Efavirenz Promotes β-Secretase Expression and Increased Aβ1-40,42 via Oxidative Stress and Reduced Microglial Phagocytosis: Implications for HIV Associated Neurocognitive Disorders (HAND)

(2014) Lecia A. M. Brown et al.   PLoS One

Stepped-Dose Versus Full-Dose Efavirenz for HIV Infection and Neuropsychiatric Adverse Events

(2013) Alicia Gutiérrez-Valencia   ANNALS OF INTERNAL MEDICINE

Protein-Free Efavirenz Concentrations in Cerebrospinal Fluid and Blood Plasma Are Equivalent: Applying the Law of Mass Action To Predict Protein-Free Drug Concentration

(2013) L. B. Avery et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Efficacy and Safety 48 Weeks after Switching from Efavirenz to Rilpivirine Using Emtricitabine/Tenofovir Disoproxil Fumarate–Based Single-Tablet Regimens

(2013) Anthony M. Mills et al.   HIV CLINICAL TRIALS

A Randomized Double-Blind Comparison of Coformulated Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Versus Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate for Initial Treatment of HIV-1 Infection

(2013) Andrew Zolopa et al.   JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES

Durable Efficacy and Safety of Raltegravir Versus Efavirenz When Combined With Tenofovir/Emtricitabine in Treatment-Naive HIV-1–Infected Patients

(2013) Jürgen K. Rockstroh et al.   JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES

Antiretroviral agents increase NO production in gp120/IFNγ-stimulated cultures of rat microglia via an arginase-dependent mechanism

(2013) Lucia Lisi et al.   JOURNAL OF NEUROIMMUNOLOGY

8-Hydroxy-efavirenz, the Primary Metabolite of the Antiretroviral Drug Efavirenz, Stimulates the Glycolytic Flux in Cultured Rat Astrocytes

(2013) Maria Brandmann et al.   NEUROCHEMICAL RESEARCH

The HIV Antiretroviral Drug Efavirenz has LSD-Like Properties

(2013) Michael B Gatch et al.   NEUROPSYCHOPHARMACOLOGY

Dolutegravir plus Abacavir–Lamivudine for the Treatment of HIV-1 Infection

(2013) Sharon L. Walmsley et al.   NEW ENGLAND JOURNAL OF MEDICINE

High predictive value of CYP2B6 SNPs for steady-state plasma efavirenz levels in South African HIV/AIDS patients

(2013) Marelize Swart et al.   Pharmacogenetics and Genomics

Discontinuation of efavirenz therapy in HIV patients due to neuropsychiatric adverse effects

(2013) Peter Derek Christian Leutscher et al.   SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES

Discontinuation of Atripla as first-line therapy in HIV-1 infected individuals

(2012) Andrew Scourfield et al.   AIDS

Efavirenz Pharmacokinetics in Cerebrospinal Fluid and Plasma over a 24-Hour Dosing Interval

(2012) Aylin Yilmaz et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Pharmacokinetic and Pharmacodynamic Analysis of Efavirenz Dose Reduction Using an In Vitro–In Vivo Extrapolation Model

(2012) M Siccardi et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

CSF Penetration by Antiretroviral Drugs

(2012) Christine Eisfeld et al.   CNS DRUGS

Antiretroviral neurotoxicity

(2012) Kevin Robertson et al.   JOURNAL OF NEUROVIROLOGY

NNRTIs: Pharmacological data

(2012) P. Dellamonica et al.   MEDECINE ET MALADIES INFECTIEUSES

Genome-wide association study of plasma efavirenz pharmacokinetics in AIDS Clinical Trials Group protocols implicates several CYP2B6 variants

(2012) Emily R. Holzinger et al.   Pharmacogenetics and Genomics

A randomized cross-over study to compare raltegravir and efavirenz (SWITCH-ER study)

(2011) Alain Nguyen et al.   AIDS

Phase 2 double-blind, randomized trial of etravirine versus efavirenz in treatment-naive patients

(2011) Brian Gazzard et al.   AIDS

The antiretroviral protease inhibitors indinavir and nelfinavir stimulate Mrp1-mediated GSH export from cultured brain astrocytes

(2011) Maria Brandmann et al.   JOURNAL OF NEUROCHEMISTRY

Non-Nucleoside Reverse Transcriptase Inhibitors Efavirenz and Nevirapine Inhibit Cytochrome C Oxidase in Mouse Brain Regions

(2011) Emilio L. Streck et al.   NEUROCHEMICAL RESEARCH

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

(2011) N. Ciccarelli et al.   NEUROLOGY

Prevalence of Congenital Anomalies in Infants With In Utero Exposure to Antiretrovirals

(2011) Katherine M. Knapp et al.   PEDIATRIC INFECTIOUS DISEASE JOURNAL

Mitochondrial interference by anti-HIV drugs: mechanisms beyond Pol-γ inhibition

(2011) Nadezda Apostolova et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Central nervous system disorders after starting antiretroviral therapy in South Africa

(2010) Valerie Asselman et al.   AIDS

A phase IV, double-blind, multicentre, randomized, placebo-controlled, pilot study to assess the feasibility of switching individuals receiving efavirenz with continuing central nervous system adverse events to etravirine

(2010) Laura Waters et al.   AIDS

No Evidence for Induction of ABC Transporters in Peripheral Blood Mononuclear Cells in Humans after 14 Days of Efavirenz Treatment

(2010) J. Burhenne et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Enhanced oxidative stress and increased mitochondrial mass during Efavirenz-induced apoptosis in human hepatic cells

(2010) N Apostolova et al.   BRITISH JOURNAL OF PHARMACOLOGY

Efavirenz Primary and Secondary Metabolism In Vitro and In Vivo: Identification of Novel Metabolic Pathways and Cytochrome P450 2A6 as the Principal Catalyst of Efavirenz 7-Hydroxylation

(2010) E. T. Ogburn et al.   DRUG METABOLISM AND DISPOSITION

Inhibition of mitochondrial function by efavirenz increases lipid content in hepatic cells

(2010) Ana Blas-García et al.   HEPATOLOGY

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

(2010) David B. Clifford et al.   HIV CLINICAL TRIALS

Implications of Efavirenz for Neuropsychiatry: A Review

(2010) G. I. T. Cavalcante et al.   INTERNATIONAL JOURNAL OF NEUROSCIENCE

Haplotype structure of CYP2B6 and association with plasma efavirenz concentrations in a Chilean HIV cohort

(2010) D. F. Carr et al.   JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY

Efavirenz concentrations in CSF exceed IC50 for wild-type HIV

(2010) B. M. Best et al.   JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY

Neurocognitive effects of treatment interruption in stable HIV-positive patients in an observational cohort

(2010) K. R. Robertson et al.   NEUROLOGY

Presence of the CYP2B6 516G> T polymorphism, increased plasma Efavirenz concentrations and early neuropsychiatric side effects in South African HIV-infected patients

(2010) Verena Gounden et al.   AIDS Research and Therapy

Influence of the Cytochrome P450 2B6 Genotype on Population Pharmacokinetics of Efavirenz in Human Immunodeficiency Virus Patients

(2009) S. E. Cabrera et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

CYP2B6(c.516G→T) andCYP2A6(*9B and/or *17) polymorphisms are independent predictors of efavirenz plasma concentrations in HIV-infected patients

(2009) Awewura Kwara et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Glucuronidation of the Antiretroviral Drug Efavirenz by UGT2B7 and an in Vitro Investigation of Drug-Drug Interaction with Zidovudine

(2009) A.-S. Belanger et al.   DRUG METABOLISM AND DISPOSITION

Efavirenz Dose Reduction Is Safe in Patients With High Plasma Concentrations and May Prevent Efavirenz Discontinuations

(2009) Matthijs van Luin et al.   JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES

Association of high T allele frequency of CYP2B6 G516T polymorphism among ethnic south Indian HIV-infected patients with elevated plasma efavirenz and nevirapine

(2009) G. Ramachandran et al.   JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY

Influence of liver fibrosis stage on plasma levels of efavirenz in HIV-infected patients with chronic hepatitis B or C

(2009) J.-L. Meynard et al.   JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY

Anti-HIV Drugs Nevirapine and Efavirenz Affect Anxiety-Related Behavior and Cognitive Performance in Mice

(2009) Pedro R. T. Romão et al.   NEUROTOXICITY RESEARCH

Pharmacokinetics of Plasma Efavirenz and CYP2B6 Polymorphism in Southern Chinese

(2009) Kin Wang To et al.   THERAPEUTIC DRUG MONITORING

Glycolysis: a bioenergetic or a survival pathway?

(2009) Juan P. Bolaños et al.   TRENDS IN BIOCHEMICAL SCIENCES

Validation of the CNS Penetration-Effectiveness Rank for Quantifying Antiretroviral Penetration Into the Central Nervous System

(2008) Scott Letendre   ARCHIVES OF NEUROLOGY

Effect of Treatment With Efavirenz on Neuropsychiatric Adverse Events of Interferon in HIV/HCV-Coinfected Patients

(2008) Carmen Quereda et al.   JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES

Effects of the HIV treatment drugs nevirapine and efavirenz on brain creatine kinase activity

(2008) Emilio L. Streck et al.   METABOLIC BRAIN DISEASE

The pharmacokinetics of methadone in HIV-positive patients receiving the non-nucleoside reverse transcriptase inhibitor efavirenz

(2003) Susan M. Clarke et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY