The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Efavirenz: What is known about the cellular mechanisms responsible for its adverse effects
Abstract
The HIV infection remains an important health problem worldwide. However, due to the efficacy of combined antiretroviral therapy (cART), it has ceased to be a mortal condition, becoming a chronic disease instead. Efavirenz, the most prescribed non-nucleoside analogue reverse transcriptase inhibitor (NNRTI), has been a key component of cART since its commercialization in 1998. Though still a drug of choice in many countries, its primacy has been challenged by the arrival of newer antiretroviral agents with better toxicity profiles and treatment adherence. The major side effects related to EFV have been widely described in clinical studies, however the mechanisms that participate in their pathogenesis remain largely ununderstood. This review provides an insight into the cellular and molecular mechanisms responsible for the development of the most significant undesired effects induced by efavirenz, both short- and long-term, revealed by in vitro and in vivo experimental pharmacological research. Growing evidence implicates the drug in energy metabolism, mitochondrial function, and other cellular processes involved in stress responses including oxidative stress, inflammation and autophagy.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“However, when given to HIV patients at high doses, efavirenz has significant adverse effects that include neurotoxicity (Apostolova et al., 2017).”
From Cholesterol Metabolism Is a Druggable Axis that Independently Regulates Tau and Amyloid-β in iPSC-Derived Alzheimer’s Disease Neurons (2019) · cites this paper as Apostolova et al., 2017
Citations
Cites
Heaton, R. K., Clifford, D. B., Franklin, D. R., Woods, S. P., Ake, C., Vaida, F., Ellis, R. J., Letendre, S. L., Marcotte, T. D., Atkinson, J. H., et al. (2010) · Neurology · doi:10.1212/wnl.0b013e318200d727 · Cited by 2,353
Research works printed but not linked: 104
- Abers, 2014, Neurological and psychiatric adverse effects of antiretroviral drugs, CNS Drugs, 28, 131, 10.1007/s40263-013-0132-4 · DOI
- Angel-Moreno-Maroto, 2006, Severe efavirenz-induced hypersensitivity syndrome (not-DRESS) with acute renal failure, J. Infect., 52, e39, 10.1016/j.jinf.2005.05.020 · DOI
- Aouri, 2016, Swiss HIV cohort study. In vivo profiling and distribution of known and novel phase I and phase II metabolites of Efavirenz in plasma, urine, and cerebrospinal fluid, Drug Metab. Dispos., 44, 151, 10.1124/dmd.115.065839 · DOI
- Apostolova, 2010, Enhanced oxidative stress and increased mitochondrial mass during efavirenz-induced apoptosis in human hepatic cells, Br. J. Pharmacol., 160, 2069, 10.1111/j.1476-5381.2010.00866.x · DOI
- Apostolova, 2011, Compromising mitochondrial function with the antiretroviral drug efavirenz induces cell survival-promoting autophagy, Hepatology, 54, 1009, 10.1002/hep.24459 · DOI
- Apostolova, 2013, ER stress in human hepatic cells treated with Efavirenz: mitochondria again, J. Hepatol., 59, 780, 10.1016/j.jhep.2013.06.005 · DOI
- Apostolova, 2015, Involvement of nitric oxide in the mitochondrial action of efavirenz: a differential effect on neurons and glial cells, J. Infect. Dis., 211, 1953, 10.1093/infdis/jiu825 · DOI
- Arendt, 2007, Neuropsychiatric side effects of efavirenz therapy, Expert Opin. Drug Saf., 6, 147, 10.1517/14740338.6.2.147 · DOI
- Bertrand, 2015, Dysregulation of endoplasmic reticulum stress and autophagic responses by the antiretroviral drug efavirenz, Mol. Pharmacol. 2015, 88, 304
- Bertrand, 2016, Antiretroviral treatment with efavirenz disrupts the blood-brain barrier integrity and increases stroke severity, Sci. Rep., 6, 39738, 10.1038/srep39738 · DOI
- Best, 2011, Efavirenz concentrations in CSF exceed IC50 for wild-type HIV, J. Antimicrob. Chemother., 66, 354, 10.1093/jac/dkq434 · DOI
- Blas-García, 2010, Inhibition of mitochondrial function by efavirenz increases lipid content in hepatic cells, Hepatology, 52, 115, 10.1002/hep.23647 · DOI
- Blas-García, 2014, Lack of mitochondrial toxicity of darunavir, raltegravir and rilpivirine in neurons and hepatocytes: a comparison with efavirenz, J. Antimicrob. Chemother., 69, 2995, 10.1093/jac/dku262 · DOI
- Bissinger, 2015, Efavirenz induced suicidal death of human erythrocytes, Cell. Physiol. Biochem., 37, 2496, 10.1159/000438602 · DOI
- Bossi, 2000, Hypersensitivity syndrome associated with efavirenz therapy, Clin. Infect. Dis., 30, 227, 10.1086/313629 · DOI
- Brandmann, 2012, The antiretroviral protease inhibitors indinavir and nelfinavir stimulate Mrp1-mediated GSH export from cultured brain astrocytes, J. Neurochem., 120, 78, 10.1111/j.1471-4159.2011.07544.x · DOI
- Brandmann, 2013, 8-Hydroxy-efavirenz, the primary metabolite of the antiretroviral drug Efavirenz, stimulates the glycolytic flux in cultured rat astrocytes, Neurochem. Res., 38, 2524, 10.1007/s11064-013-1165-2 · DOI
- Brown, 2014, Efavirenz promotes β-secretase expression and increased Aβ1-40,42 via oxidative stress and reduced microglial phagocytosis: implications for HIV associated neurocognitive disorders (HAND), PLoS One, 9, e95500, 10.1371/journal.pone.0095500 · DOI
- Brown, 2010, Association between initiation of antiretroviral therapy with efavirenz and decreases in 25-hydroxyvitamin D, Antivir. Ther., 15, 425, 10.3851/IMP1502 · DOI
- Bumpus, 2011, Efavirenz and 8-hydroxyefavirenz induce cell death via a JNK- and BimEL-dependent mechanism in primary human hepatocytes, Toxicol. Appl. Pharmacol., 257, 227, 10.1016/j.taap.2011.09.008 · DOI
- Burger, 2006, Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz: the effect of gender, race, and CYP2B6 polymorphism, Br. J. Clin. Pharmacol., 61, 148, 10.1111/j.1365-2125.2005.02536.x · DOI
- Cardenas, 2009, Evidence for ongoing brain injury in human immunodeficiency virus-positive patients treated with antiretroviral therapy, J. Neurovirol., 15, 324, 10.1080/13550280902973960 · DOI
- Carr, 2010, Haplotype structure of CYP2B6 and association with plasma efavirenz concentrations in a Chilean HIV cohort, J. Antimicrob. Chemother., 65, 1889, 10.1093/jac/dkq260 · DOI
- Cavalcante, 2010, Implications of Efavirenz for neuropsychiatry: a review, Int. J. Neurosci., 120, 739, 10.3109/00207454.2010.520541 · DOI
- Cavalcante, 2017, HIV antiretroviral drug Efavirenz induces anxiety-like and depression-like behavior in rats: evaluation of neurotransmitter alterations in the striatum, Eur. J. Pharmacol., 799, 7, 10.1016/j.ejphar.2017.02.009 · DOI
- Ciccarelli, 2011, Efavirenz associated with cognitive disorders in otherwise asymptomatic HIV-infected patients, Neurology, 76, 1403, 10.1212/WNL.0b013e31821670fb · DOI
- Dave, 2015, Antiretroviral therapy, especially Efavirenz, is associated with low bone mineral density in HIV-infected South Africans, PLoS One, 10, e0144286, 10.1371/journal.pone.0144286 · DOI
- Davidson, 2013, Valproic acid inhibits the release of soluble CD40L induced by non-nucleoside reverse transcriptase inhibitors in human immunodeficiency virus infected individuals, PLoS One, 8, e59950, 10.1371/journal.pone.0059950 · DOI
- De Clercq, 2009, Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV, Int. J. Antimicrob. Agents, 33, 307, 10.1016/j.ijantimicag.2008.10.010 · DOI · Paper page
- Díaz-Delfín, 2011, Effects of nevirapine and efavirenz on human adipocyte differentiation, gene expression, and release of adipokines and cytokines, Antivir. Res, 91, 112, 10.1016/j.antiviral.2011.04.018 · DOI
- Dong, 2013, Efavirenz induces autophagy and aberrant differentiation in normal human keratinocytes, Int. J. Mol. Med., 31, 1305, 10.3892/ijmm.2013.1327 · DOI
- Eisfeld, 2013, CSF penetration by antiretroviral drugs, CNS Drugs, 27, 31, 10.1007/s40263-012-0018-x · DOI
- El Hadri, 2004, In vitro suppression of the lipogenic pathway by the nonnucleoside reverse transcriptase inhibitor efavirenz in 3T3 and human preadipocytes or adipocytes, J. Biol. Chem., 279, 15130, 10.1074/jbc.M312875200 · DOI
- Faggian, 2005, Recreational substance use and tolerance of efavirenz in HIV-1 infected patients, AIDS Care, 17, 908, 10.1080/09540120500038371 · DOI
- Faltz, 2017, Effect of the anti-retroviral drugs efavirenz, tenofovir and emtricitabine on endothelial cell function: role of PARP, Cardiovasc. Toxicol., 10.1007/s12012-016-9397-4 · DOI
- Fox, 2011, Improvement in vitamin D deficiency following antiretroviral regime change: results from the MONET trial, AIDS Res. Hum. Retrovir., 27, 29, 10.1089/aid.2010.0081 · DOI
- Fumaz, 2005, Long-term neuropsychiatric disorders on efavirenz-based approaches: quality of life, psychologic issues, and adherence, J. Acquir. Immune Defic. Syndr., 38, 560, 10.1097/01.qai.0000147523.41993.47 · DOI
- Funes, 2014, Neuronal bioenergetics and acute mitochondrial dysfunction: a clue to understanding the central nervous system side effects of efavirenz, J. Infect. Dis., 210, 1385, 10.1093/infdis/jiu273 · DOI
- Funes, 2015, Efavirenz alters mitochondrial respiratory function in cultured neuron and glial cell lines, J. Antimicrob. Chemother., 70, 2249, 10.1093/jac/dkv098 · DOI
- Gallego-Escuredo, 2010, Differential effects of efavirenz and lopinavir/ritonavir on human adipocyte differentiation, gene expression and release of adipokines and pro-inflammatory cytokines, Curr. HIV Res., 8, 545, 10.2174/157016210793499222 · DOI
- Gatch, 2013, The HIV antiretroviral drug efavirenz has LSD-like properties, Neuropsychopharmacology, 38, 2373, 10.1038/npp.2013.135 · DOI
- Gazzard, 2011, Phase 2 double-blind, randomized trial of etravirine versus efavirenz in treatment-naive patients: 48-week results, AIDS, 25, 2249, 10.1097/QAD.0b013e32834c4c06 · DOI
- Gibellini, 2015, Different origin of adipogenic stem cells influences the response to antiretroviral drugs, Exp. Cell. Res., 337, 160, 10.1016/j.yexcr.2015.07.031 · DOI
- Gomez-Sucerquia, 2012, Profile of stress and toxicity gene expression in human hepatic cells treated with Efavirenz, Antivir. Res., 94, 232, 10.1016/j.antiviral.2012.04.003 · DOI
- Gounden, 2010, Presence of the CYP2B6 516G> T polymorphism, increased plasma Efavirenz concentrations and early neuropsychiatric side effects in South African HIV-infected patients, AIDS Res. Ther., 7, 32, 10.1186/1742-6405-7-32 · DOI
- Gupta, 2012, Worsening endothelial function with efavirenz compared to protease inhibitors: a 12-month prospective study, PLoS One, 7, e45716, 10.1371/journal.pone.0045716 · DOI
- Hariparsad, 2004, Induction of CYP3A4 by efavirenz in primary human hepatocytes, comparison with rifampin and phenobarbital, J. Clin. Pharmacol., 44, 1273, 10.1177/0091270004269142 · DOI
- Harjivan, 2014, The phenolic metabolites of the anti-HIV drug efavirenz: evidence for distinct reactivities upon oxidation with Frémy's salt, Eur. J. Med. Chem., 74, 7, 10.1016/j.ejmech.2013.12.022 · DOI
- Haubrich, 2009, Metabolic outcomes in a randomized trial of nucleoside, nonnucleoside and protease inhibitor-sparing regimens for initial HIV treatment, AIDS, 23, 1109, 10.1097/QAD.0b013e32832b4377 · DOI
- Heaton, 2011, HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. CHARTER Group; HNRC Group, J. Neurovirol., 17, 3, 10.1007/s13365-010-0006-1 · DOI
- Hecht, 2015, Efavirenz has the highest anti-proliferative effect of non-nucleoside reverse transcriptase inhibitors against pancreatic cancer cells, PLoS One, 10, e0130277, 10.1371/journal.pone.0130277 · DOI
- Hecht, 2013, Cytotoxic effect of efavirenz is selective against cancer cells and associated with the cannabinoid system, AIDS, 27, 2031, 10.1097/QAD.0b013e3283625444 · DOI
- Hulgan, 2003, Oxidant stress is increased during treatment of human immunodeficiency virus infection, Clin. Infect. Dis., 37, 1711, 10.1086/379776 · DOI
- Imaizumi, 2015, Mechanisms of cell death pathway activation following drug-induced inhibition of mitochondrial complex I, Redox Biol., 4, 279, 10.1016/j.redox.2015.01.005 · DOI
- Jamaluddin, 2010, Non-nucleoside reverse transcriptase inhibitor efavirenz increases monolayer permeability of human coronary artery endothelial cells, Atherosclerosis, 208, 104, 10.1016/j.atherosclerosis.2009.07.029 · DOI
- Jin, 2016, HIV non-nucleoside reverse transcriptase inhibitor efavirenz reduces neural stem cell proliferation in vitro and in vivo, Cell Transplant., 25, 1967, 10.3727/096368916X691457 · DOI
- Kappelhoff, 2005, Are adverse events of nevirapine and efavirenz related to plasma concentrations?, Antivir. Ther., 10, 489, 10.1177/135965350501000404 · DOI
- Kwara, 2009, CYP2B6 (c.516G-->T) and CYP2A6 (*9B and/or *17) polymorphisms are independent predictors of efavirenz plasma concentrations in HIV-infected patients, Br. J. Clin. Pharmacol., 67, 427, 10.1111/j.1365-2125.2009.03368.x · DOI
- Kenedi, 2011, A systematic review of the psychiatric side-effects of efavirenz, AIDS Behav., 15, 1803, 10.1007/s10461-011-9939-5 · DOI
- Landriscina, 2005, Reverse transcriptase inhibitors down-regulate cell proliferation in vitro and in vivo and restore thyrotropin signaling and iodine uptake in human thyroid anaplastic carcinoma, J. Clin. Endocrinol. Metab., 90, 5663, 10.1210/jc.2005-0367 · DOI
- Li, 2008, Nitrosative stress with HIV dementia causes decreased L-prostaglandin D synthase activity, Neurology, 70, 1753, 10.1212/01.wnl.0000282761.19578.35 · DOI
- Lisi, 2014, Antiretroviral agents increase NO production in gp120/IFNγ-stimulated cultures of rat microglia via an arginase-dependent mechanism, J. Neuroimmunol., 266, 24, 10.1016/j.jneuroim.2013.10.013 · DOI
- Lochet, 2003, Long-term assessment of neuropsychiatric adverse reactions associated with efavirenz, HIV Med., 4, 62, 10.1046/j.1468-1293.2003.00136.x · DOI
- Manfredi, 2005, An extremely different dysmetabolic profile between the two available nonnucleoside reverse transcriptase inhibitors: efavirenz and nevirapine, J. Acquir. Immune Defic. Syndr., 38, 236, 10.1097/01.qai.0000143037.70120.fc · DOI
- Marra, 2009, Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance, AIDS, 23, 1359, 10.1097/QAD.0b013e32832c4152 · DOI
- Marzolini, 2001, Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients, AIDS, 15, 71, 10.1097/00002030-200101050-00011 · DOI
- Muñoz-Moreno, 2009, Neuropsychiatric symptoms associated with efavirenz: prevalence, correlates, and management. A neurobehavioral review, AIDS Rev., 11, 103
- Moure, 2016, Impact of elvitegravir on human adipocytes: alterations in differentiation, gene expression and release of adipokines and cytokines, Antivir. Res., 132, 59, 10.1016/j.antiviral.2016.05.013 · DOI
- Neukam, 2011, Liver toxicity associated with antiretroviral therapy including efavirenz or ritonavir-boosted protease inhibitors in a cohort of HIV/hepatitis C virus co-infected patients, J. Antimicrob. Chemother., 66, 2605, 10.1093/jac/dkr357 · DOI
- Ogburn, 2010, 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, Drug Metab. Dispos., 38, 1218, 10.1124/dmd.109.031393 · DOI
- O'Mahony, 2005, Efavirenz induces depressive-like behaviour, increased stress response and changes in the immune response in rats, Neuroimmunomodulation, 12, 293, 10.1159/000087107 · DOI
- Orden, 2014, Efavirenz induces interactions between leucocytes and endothelium through the activation of Mac-1 and gp150,95, J. Antimicrob. Chemother., 69, 995, 10.1093/jac/dkt468 · DOI
- Pereira, 2008, Efavirenz concentrations in HIV-infected patients with and without viral hepatitis, Br. J. Clin. Pharmacol., 66, 551, 10.1111/j.1365-2125.2008.03238.x · DOI
- Pérez-Molina, 2002, Safety and tolerance of efavirenz in different antiretroviral regimens: results from a national multicenter prospective study in 1,033 HIV-infected patients, HIV Clin. Trials, 3, 279, 10.1310/3Q91-YT2D-BUT4-8HN6 · DOI
- Pérez-Molina, 2008, The role of efavirenz compared with protease inhibitors in the body fat changes associated with highly active antiretroviral therapy, J. Antimicrob. Chemother., 62, 234, 10.1093/jac/dkn191 · DOI
- Peyriere, 2001, Management of sudden psychiatric disorders related to efavirenz, AIDS, 15, 1323, 10.1097/00002030-200107060-00021 · DOI
- Pilon, 2002, Induction of apoptosis by a nonnucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitor, Antimicrob. Agents Chemother., 46, 2687, 10.1128/AAC.46.8.2687-2691.2002 · DOI
- Pittoggi, 2008, In vitro evidence for a new therapeutic approach in renal cell carcinoma, Int. Braz. J. Urol., 34, 492, 10.1590/S1677-55382008000400012 · DOI
- Purnell, 2014, Efavirenz induces neuronal autophagy and mitochondrial alterations, J. Pharmacol. Exp. Ther., 351, 250, 10.1124/jpet.114.217869 · DOI
- Ramachandran, 2009, Association of high T allele frequency of CYP2B6 G516T polymorphism among ethnic south Indian HIV-infected patients with elevated plasma efavirenz and nevirapine, J. Antimicrob. Chemother., 63, 841, 10.1093/jac/dkp033 · DOI
- Riddler, 2008, Class-sparing regimens for initial treatment of HIV-1 infection, N. Engl. J. Med., 358, 2095, 10.1056/NEJMoa074609 · DOI
- Rihs, 2006, Efavirenz and chronic neuropsychiatric symptoms: a cross-sectional case control study, HIV Med., 7, 544, 10.1111/j.1468-1293.2006.00419.x · DOI
- Rivero, 2007, Liver toxicity induced by non-nucleoside reverse transcriptase inhibitors, J. Antimicrob. Chemother., 59, 342, 10.1093/jac/dkl524 · DOI
- Rodríguez de la Concepción, 2005, Reverse transcriptase inhibitors alter uncoupling protein-1 and mitochondrial biogenesis in brown adipocytes, Antivir. Ther., 10, 515, 10.1177/135965350501000407 · DOI
- Romão, 2011, Anti-HIV drugs nevirapine and efavirenz affect anxiety-related behavior and cognitive performance in mice, Neurotox., Res., 19, 73, 10.1007/s12640-009-9141-y · DOI
- Schwartz, 2014, Relationship of vitamin D, HIV, HIV treatment, and lipid levels in the Women's Interagency HIV Study of HIV-infected and uninfected women in the United States, J. Int. Assoc. Provid. AIDS Care, 13, 250, 10.1177/2325957413506748 · DOI
- Schweinsburg, 2005, Brain mitochondrial injury in human immunodeficiency virus-seropositive (HIV+) individuals taking nucleoside reverse transcriptase inhibitors, J. Neurovirol., 11, 356, 10.1080/13550280591002342 · DOI
- Scourfield, 2012, Discontinuation of Atripla as first-line therapy in HIV-1 infected individuals, AIDS, 26, 1399, 10.1097/QAD.0b013e328353b047 · DOI
- Sharma, 2013, Agonism of human pregnane X receptor by rilpivirine and etravirine: comparison with first generation non-nucleoside reverse transcriptase inhibitors, Biochem. Pharmacol., 85, 1700, 10.1016/j.bcp.2013.04.002 · DOI
- Shikuma, 2007, Metabolic effects of protease inhibitor-sparing antiretroviral regimens given as initial treatment of HIV-1 Infection (AIDS Clinical Trials Group Study A5095), J. Acquir. Immune Defic. Syndr., 44, 540, 10.1097/QAI.0b013e318031d5a0 · DOI
- Staszewski, 1999, Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team, N. Engl. J. Med., 341, 1865, 10.1056/NEJM199912163412501 · DOI
- Streck, 2008, Effects of the HIV treatment drugs nevirapine and efavirenz on brain creatine kinase activity, Metab. Brain Dis., 23, 485, 10.1007/s11011-008-9109-2 · DOI
- Streck, 2011, Non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine inhibit cytochrome C oxidase in mouse brain regions, Neurochem. Res., 36, 962, 10.1007/s11064-011-0432-3 · DOI
- Tashima, 1999, Cerebrospinal fluid human immunodeficiency virus type 1 (HIV-1) suppression and efavirenz drug concentrations in HIV-1-infected patients receiving combination therapy, J. Infect. Dis., 180, 862, 10.1086/314945 · DOI
- Tovar-y-Romo, 2012, Dendritic spine injury induced by the 8-hydroxy metabolite of efavirenz, J. Pharmacol. Exp. Ther., 343, 696, 10.1124/jpet.112.195701 · DOI
- Walker, 2002, Increased long-term mitochondrial toxicity in combinations of nucleoside analogue reverse-transcriptase inhibitors, AIDS, 16, 2165, 10.1097/00002030-200211080-00009 · DOI
- Wang, 2015, The acute extracellular flux (XF) assay to assess compound effects on mitochondrial function, J. Biomol. Screen., 20, 422, 10.1177/1087057114557621 · DOI
- Wang, 2013, High prevalence of HIV-associated neurocognitive disorder in HIV-infected patients with a baseline CD4 count ≤ 350 cells/μl in Shanghai, China, Biosci. Trends, 7, 284
- Ward, 2003, The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity, J. Pharmacol. Exp. Ther., 306, 287, 10.1124/jpet.103.049601 · DOI
- Weiss, 2009, Induction of multiple drug transporters by efavirenz, J. Pharmacol. Sci., 109, 242, 10.1254/jphs.08209FP · DOI
- Weiß, 2016, Efavirenz causes oxidative stress, endoplasmic reticulum stress, and autophagy in endothelial cells, Cardiovasc. Toxicol., 16, 90, 10.1007/s12012-015-9314-2 · DOI
- Welz, 2010, Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase, AIDS, 24, 1923, 10.1097/QAD.0b013e32833c3281 · DOI
- Winston, 2012, Dynamics of cognitive change in HIV-infected individuals commencing three different initial antiretroviral regimens: a randomized, controlled study, HIV Med., 13, 245, 10.1111/j.1468-1293.2011.00962.x · DOI
- Yilmaz, 2012, Efavirenz pharmacokinetics in cerebrospinal fluid and plasma over a 24-hour dosing interval, Antimicrob. Agents Chemother., 56, 4583, 10.1128/AAC.06311-11 · DOI
Cited by
Sorted by citations
van der Kant, R., Langness, V. F., Herrera, C. M., Williams, D. A., Fong, L. K., Leestemaker, Y., Steenvoorden, E., Rynearson, K. D., Brouwers, J. F., Helms, J. B., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2018.12.013 · Cited by 350
Metadata
- Authors
- Apostolova, N., Blas-Garcia, A., Galindo, M. J., & Esplugues, J. V.
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 812
- Pages
- 163-173
- ISSN
- 0014-2999
- Cited by
- 49
- References
- 1
- Language
- en
- Funders
- Federación Española de Enfermedades Raras (JCI-2012–15124)
- Ministerio de Economía y Competitividad (PI14/00312)
- Generalitat Valenciana (PROMETEOII/2014/035)
- Instituto de Salud Carlos III
- European Regional Development Fund (CIBER CB06/04/0071, SAF2015-67678-R)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Efavirenz: What is known about the cellular mechanisms responsible for its adverse effects. https://app.cochat.ai/papers/10.1016/j.ejphar.2017.07.016
- The paper
- Apostolova, N., Blas-Garcia, A., Galindo, M. J., & Esplugues, J. V. (2017). Efavirenz: What is known about the cellular mechanisms responsible for its adverse effects. European Journal of Pharmacology. https://doi.org/10.1016/j.ejphar.2017.07.016