{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:05:33Z","timestamp":1747181133774,"version":"3.40.5"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"44","license":[{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,11,3]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>A randomized interventional phase 4 study in the Indian population confirmed the non-inferiority of the combination tenofovir\/lamivudine\/efavirenz (TLE)-400 to TLE600. The current manuscript describes in detail the safety profile and patient-reported safety outcomes obtained from the phase 4 study.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>This investigation was part of a phase 4 non-inferiority study with a blinded assessment, conducted across 17 sites in India. The duration of the study was 24 weeks. Safety endpoints assessed included all the adverse events (AEs) related to the study treatment (TLE400 and TLE600). The depression anxiety stress 21-item scale questionnaire and efavirenz-related symptom questionnaire were also used to measure depression, anxiety, stress, and patient experience.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>A total of 68 patients (52.3%) reported 261 AEs and 87 patients (64.9%) reported 379 AEs related to study treatment in TLE400 group and TLE600 group respectively, <jats:italic toggle=\"yes\">P<\/jats:italic> = .037. The reported AEs associated with central nervous system disorders were lower in the TLE400 group with 41 patients (31.5%) to 61 patients (45.5%) in the TLE600 group. The change from mean baseline value for depression anxiety stress 21-item scale at week 28 in TLE400 group and TLE600 group was \u22125.1 and \u22126.2 respectively. Similarly, the mean change from baseline score of efavirenz-related symptoms at week 28 in TLE400 group and TLE600 group were \u22125.1 and \u22124.1 respectively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion:<\/jats:title>\n            <jats:p>The low dose efavirenz (400\u2009mg) in combination with tenofovir and lamivudine had a better safety and tolerability profile than the standard dose of efavirenz (600\u2009mg) in combination with tenofovir and lamivudine. Thus, low dose efavirenz should be preferred over the standard dose.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/md.0000000000035643","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T09:09:52Z","timestamp":1701162592000},"page":"e35643","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Safety of low dose efavirenz regimen in Indian adults with HIV-1 infection: Insights from a phase 4 interventional randomised trial"],"prefix":"10.1097","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1909-7530","authenticated-orcid":false,"given":"Ameet N.","family":"Dravid","sequence":"first","affiliation":[{"name":"Department of Medicine, Poona Hospital and Research Centre, Maharashtra, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anant S.","family":"Pilawan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Government Medical College & Hospital, Maharashtra, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Anuradha","sequence":"additional","affiliation":[{"name":"Department of Medicine, Maulana Azad Medical College, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dnyanesh N.","family":"Morkar","sequence":"additional","affiliation":[{"name":"Department of Medicine, KLE Hospital, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T.","family":"Ramapuram","sequence":"additional","affiliation":[{"name":"Department of Medicine, Kasturba Medical College, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kulkarni Milind","family":"Madhukarrao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sahyadri Specialty Hospital, Maharashtra, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. Sunil","family":"Naik","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rajiv Gandhi Institute of Medical Science and RIMS Government General Hospital, Andhra Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milind","family":"Bhrusundi","sequence":"additional","affiliation":[{"name":"Department of Medicine, NKP Salve Institute of Medical Sciences and Late Mangeshkar Hospital, Maharashtra, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.R.","family":"Raveendra","sequence":"additional","affiliation":[{"name":"Department of Medicine, Bangalore Medical College and Research Institute, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siddabathuni","family":"Nageswaramma","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Guntur Government General Hospital, Andhra Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinay","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Deenanath Mangeshkar Hospital and Research Centre, Maharashtra, India."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R3-20250504","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1310\/92VR-FP24-J8GA-B49Q","article-title":"Comparison of neuropsychiatric side effects in an observational cohort of efavirenz- and protease inhibitor-treated patients.","volume":"6","author":"Hawkins","year":"2005","journal-title":"HIV Clin Trials"},{"key":"R4-20250504","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1097\/00126334-200108010-00003","article-title":"Preliminary data of a prospective study on neuropsychiatric side effects after initiation of efavirenz.","volume":"27","author":"Blanch","year":"2001","journal-title":"J Acquir Immune Defic Syndr"},{"key":"R5-20250504","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1310\/3Q91-YT2D-BUT4-8HN6","article-title":"Safety and tolerance of efavirenz in different antiretroviral regimens: results from a national multicenter prospective study in 1,033 HIV-infected patients.","volume":"3","author":"Perez-Molina","year":"2002","journal-title":"HIV Clin Trials"},{"key":"R6-20250504","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.neuropharm.2017.04.038","article-title":"The dual modulatory effects of efavirenz on GABA(A) receptors are mediated via two distinct sites.","volume":"121","author":"Huang","year":"2017","journal-title":"Neuropharmacology"},{"key":"R9-20250504","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1056\/NEJM199912163412501","article-title":"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.","volume":"341","author":"Staszewski","year":"1999","journal-title":"N Engl J Med"},{"key":"R10-20250504","doi-asserted-by":"crossref","first-page":"e01841","DOI":"10.1128\/AAC.01841-16","article-title":"Efavirenz is predicted to accumulate in brain tissue: an in silico, in vitro, and in vivo investigation.","volume":"61","author":"Curley","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"R11-20250504","doi-asserted-by":"crossref","first-page":"741","DOI":"10.4102\/sajhivmed.v18i1.741","article-title":"Efavirenz and neuropsychiatric effects.","volume":"18","author":"Dheda","year":"2017","journal-title":"South Afr J HIV Med"},{"key":"R14-20250504","doi-asserted-by":"crossref","first-page":"645","DOI":"10.3109\/00365548.2013.773067","article-title":"Discontinuation of efavirenz therapy in HIV patients due to neuropsychiatric adverse effects.","volume":"45","author":"Leutscher","year":"2013","journal-title":"Scand J Infect Dis"},{"key":"R15-20250504","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/00042560-200203010-00004","article-title":"Quality of life, emotional status, and adherence of HIV-1-infected patients treated with efavirenz versus protease inhibitor-containing regimens.","volume":"29","author":"Fumaz","year":"2002","journal-title":"J Acquir Immune Defic Syndr"},{"key":"R16-20250504","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1016\/S0140-6736(13)62187-X","article-title":"Efficacy of 400\u2009mg efavirenz versus standard 600\u2009mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial.","volume":"383","author":"Group","year":"2014","journal-title":"Lancet"},{"key":"R17-20250504","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.3390\/cells10071687","article-title":"NNRTI and liver damage: evidence of their association and the mechanisms involved.","volume":"10","author":"Benedicto","year":"2021","journal-title":"Cells"},{"key":"R18-20250504","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/j.1365-2125.2006.02619.x","article-title":"Long-term and concentration-dependent beneficial effect of efavirenz on HDL-cholesterol in HIV-infected patients.","volume":"61","author":"Pereira","year":"2006","journal-title":"Br J Clin Pharmacol"},{"key":"R19-20250504","first-page":"331","article-title":"Efavirenz-therapy in HIV-patients with underlying liver disease: importance of continuous TDM of EFV.","volume":"12","author":"Katsounas","year":"2007","journal-title":"Eur J Med Res"},{"key":"R20-20250504","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/S1473-3099(15)70060-5","article-title":"Efficacy and safety of efavirenz 400\u2009mg daily versus 600\u2009mg daily: 96-week data from the randomised, double-blind, placebo-controlled, non-inferiority ENCORE1 study.","volume":"15","author":"Group","year":"2015","journal-title":"Lancet Infect Dis"},{"key":"R21-20250504","doi-asserted-by":"crossref","first-page":"e31982","DOI":"10.1097\/MD.0000000000031982","article-title":"Efficacy and safety of 400\u2009mg efavirenz versus standard 600\u2009mg dose when taken with tenofovir and lamivudine combination in Indian adult patients with HIV-1 infection: an open-label, interventional, randomized, non-inferiority trial.","volume":"101","author":"Dravid","year":"2022","journal-title":"Medicine (Baltim)"},{"key":"R23-20250504","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/hiv.12912","article-title":"Efficacy and safety of a single-tablet regimen containing tenofovir disoproxil fumarate 300\u2009mg, lamivudine 300\u2009mg and efavirenz 400\u2009mg as a switch strategy in virologically suppressed HIV-1-infected subjects on nonnucleoside reverse transcriptase inhibitor-containing first-line antiretroviral therapy in Pune, India.","volume":"21","author":"Dravid","year":"2020","journal-title":"HIV Med"},{"key":"R24-20250504","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1097\/QAI.0b013e3181b061e6","article-title":"Efavirenz dose reduction is safe in patients with high plasma concentrations and may prevent efavirenz discontinuations.","volume":"52","author":"van Luin","year":"2009","journal-title":"J Acquir Immune Defic Syndr"},{"key":"R25-20250504","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1007\/s10461-011-9939-5","article-title":"A systematic review of the psychiatric side-effects of efavirenz.","volume":"15","author":"Kenedi","year":"2011","journal-title":"AIDS Behav"},{"key":"R26-20250504","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1097\/00002030-200101050-00011","article-title":"Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients.","volume":"15","author":"Marzolini","year":"2001","journal-title":"AIDS"},{"key":"R27-20250504","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s11481-019-09886-7","article-title":"CNS neurotoxicity of antiretrovirals.","volume":"16","author":"Lanman","year":"2021","journal-title":"J Neuroimmune Pharmacol"},{"key":"R28-20250504","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s13365-017-0573-5","article-title":"Central nervous system-penetrating antiretrovirals impair energetic reserve in striatal nerve terminals.","volume":"23","author":"Stauch","year":"2017","journal-title":"J Neurovirol"},{"key":"R29-20250504","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/j.1468-1293.2006.00419.x","article-title":"Efavirenz and chronic neuropsychiatric symptoms: a cross-sectional case control study.","volume":"7","author":"Rihs","year":"2006","journal-title":"HIV Med"},{"key":"R30-20250504","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1086\/380791","article-title":"Analyzing sleep abnormalities in HIV-infected patients treated with Efavirenz.","volume":"38","author":"Gallego","year":"2004","journal-title":"Clin Infect Dis"}],"container-title":["Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/MD.0000000000035643","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T02:20:30Z","timestamp":1746325230000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/MD.0000000000035643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,3]]},"references-count":23,"journal-issue":{"issue":"44","published-print":{"date-parts":[[2023]]}},"URL":"https:\/\/doi.org\/10.1097\/md.0000000000035643","relation":{},"ISSN":["0025-7974","1536-5964"],"issn-type":[{"type":"print","value":"0025-7974"},{"type":"electronic","value":"1536-5964"}],"subject":[],"published":{"date-parts":[[2023,11,3]]}}}