{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:57:29Z","timestamp":1791269849945,"version":"4.1.0"},"reference-count":28,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2007,7,1]],"date-time":"2007-07-01T00:00:00Z","timestamp":1183248000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The patterns and reasons for antiretroviral therapy (ART) drug substitutions are poorly described in resource-limited settings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Time to and reason for drug substitution were recorded in treatment-naive adults receiving ART in two primary care treatment programmes in Cape Town. The cumulative proportion of patients having therapy changed because of toxicity was described for each drug, and associations with these changes were explored in multivariate models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Analysis included 2,679 individuals followed for a median of 11 months. Median CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell count at baseline was 85 cells\/\u03bcl. Mean weight was 59 kg, mean age was 32 years and 71% were women. All started non-nucleoside reverse transcriptase inhibitor-based ART (60% on efavrienz) and 75% started on stavudine (d4T). After 3 years, 75% remained in care on-site, of whom 72% remained on their initial regimen. Substitutions due to toxicity of nevirapine (8% by 3 years), efavirenz (2%) and zidovudine (8%) occurred early. Substitutions on d4T occurred in 21% of patients by 3 years, due to symptomatic hyper-lactataemia (5%), lipodystrophy (9%) or peripheral neuropathy (6%), and continued to accumulate over time. Those at greatest risk of hyperlactataemia or lipodystrophy were women on ART \u22656 months, weighing \u226575 kg at baseline.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>A high proportion of adult patients are able to tolerate their initial ART regimen for up to 3 years. In most instances treatment-limiting toxicities occur early, but continue to accumulate over time in patients on d4T. Whilst awaiting other treatment options, the risks of known toxicities could be minimized through early identification of patients at the highest risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/135965350701200508","type":"journal-article","created":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T12:20:14Z","timestamp":1649938814000},"page":"753-760","source":"Crossref","is-referenced-by-count":98,"title":["Substitutions Due to Antiretroviral Toxicity or Contraindication in the First 3 years of Antiretroviral Therapy in a Large South African Cohort"],"prefix":"10.1177","volume":"12","author":[{"given":"Andrew","family":"Boulle","sequence":"first","affiliation":[{"name":"Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Orrell","sequence":"additional","affiliation":[{"name":"The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Health, Provincial Government of the Western Cape, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Van Cutsem","sequence":"additional","affiliation":[{"name":"M\u00e9decins Sans Fronti\u00e8res, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"McNally","sequence":"additional","affiliation":[{"name":"Department of Health, Provincial Government of the Western Cape, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Hilderbrand","sequence":"additional","affiliation":[{"name":"Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"M\u00e9decins Sans Fronti\u00e8res, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Landon","family":"Myer","sequence":"additional","affiliation":[{"name":"Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Egger","sequence":"additional","affiliation":[{"name":"Institute of Social and Preventive Medicine, University of Berne, Berne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Coetzee","sequence":"additional","affiliation":[{"name":"Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Department of Health, Provincial Government of the Western Cape, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Maartens","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Wood","sequence":"additional","affiliation":[{"name":"The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Collaboration for the International Epidemiological Databases to Evaluate Aids in Southern Africa (IeDEASA)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2007,7,1]]},"reference":[{"key":"bibr1-135965350701200508","volume-title":"Antiretroviral therapy for HIV infection in adults and adolescents in resource-limited settings: towards universal access.","author":"World Health Organization","year":"2006"},{"key":"bibr2-135965350701200508","volume-title":"Antiretroviral Treatment Guidelines","author":"National Department of Health","year":"2004","edition":"1"},{"key":"bibr3-135965350701200508","first-page":"2","volume":"8","author":"Nolan D.","year":"2003","journal-title":"J HIV Ther"},{"key":"bibr4-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1097\/00126334-200408010-00007"},{"key":"bibr5-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1177\/095632020301400507"},{"key":"bibr6-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200501030-00002"},{"key":"bibr7-135965350701200508","first-page":"722","volume":"96","author":"Geddes R.","year":"2006","journal-title":"S Afr Med 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Cape Town: Provincial Government of the Western Cape."},{"key":"bibr13-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000194802.89540.e1"},{"key":"bibr14-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1086\/507095"},{"key":"bibr15-135965350701200508","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1177\/135965350701200106","volume":"12","author":"Orrell C.","year":"2007","journal-title":"Antivir Ther"},{"key":"bibr16-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200406003-00006"},{"issue":"17","key":"bibr17-135965350701200508","first-page":"1","volume":"41","author":"Centers for Disease Control and Prevention.","year":"1992","journal-title":"MMWR Recomm Rep"},{"key":"bibr18-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602102"},{"key":"bibr19-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-1293.2002.00110.x"},{"key":"bibr20-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38369.669850.8F"},{"key":"bibr21-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200003310-00005"},{"key":"bibr22-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1097\/00042560-200204150-00010"},{"key":"bibr23-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200101260-00007"},{"key":"bibr24-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1086\/428093"},{"key":"bibr25-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2004.03.009"},{"key":"bibr26-135965350701200508","unstructured":"Meta-analysis of efficacy and safety for clinical studies of d4T 40mg versus 30mg BID in 1008 patients.\n                      XVI International AIDS Conference.\n                      13\u201318 August 2006, Toronto, Canada. Abstract ThPE0120."},{"key":"bibr27-135965350701200508","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200401230-00002"},{"key":"bibr28-135965350701200508","doi-asserted-by":"publisher","DOI":"10.2307\/2532940"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/135965350701200508","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/135965350701200508","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:54:04Z","timestamp":1777380844000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/135965350701200508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,7]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2007,7]]}},"alternative-id":["10.1177\/135965350701200508"],"URL":"https:\/\/doi.org\/10.1177\/135965350701200508","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,7]]}}}