{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T01:32:53Z","timestamp":1772155973129,"version":"3.50.1"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence, and the development of HIV resistance mutations. We aimed to evaluate 4 management strategies for children following their first episode of VF by comparing their immunologic and virologic outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We included children (&lt; 16 years of age) with VF from 8 International Epidemiologic Database to Evaluate AIDS Southern Africa cohorts, initiating combination antiretroviral therapy (cART) between 2004 and 2010, who followed one of the 4 management strategies: continuing on their failing regimen; switching to a second-line regimen; switching to a holding regimen (either lamivudine monotherapy or other non-cART regimen); discontinuing all ART. We compared the effect of management strategy on the 52-week change in CD4% and log\n                      <jats:sub>10<\/jats:sub>\n                      VL from VF, using inverse probability weighting of marginal structural linear models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Nine hundred eighty-two patients were followed over 54,168 weeks. Relative to remaining on a failing regimen, switching to second-line showed improved immunologic and virologic responses 52 weeks after VF with gains in CD4% of 1.5% (95% confidence interval [CI], 0.2\u20132.8) and declines in log\n                      <jats:sub>10<\/jats:sub>\n                      VL of -1.4 copies\/mL (95% CI, -2.0, -0.8), while switching to holding regimens or discontinuing treatment had worse immunologic (-5.4% (95% CI, -12.1, 1.3) and -5.6% (95% CI, -15.4, 4.1) and virologic outcomes (0.2 (95% CI, -3.6, 4.1) and 0.8 (95% CI, -0.6, 2.1), respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The results provide useful guidance for managing children with VF. Consideration should be given to switching children failing first-line cART to second-line, given the improved virologic and immune responses when compared with other strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/inf.0000000000002156","type":"journal-article","created":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T17:40:08Z","timestamp":1533145208000},"page":"400-405","source":"Crossref","is-referenced-by-count":4,"title":["What Should We Do When HIV-positive Children Fail First-line Combination Antiretroviral Therapy? A Comparison of 4 ART Management Strategies"],"prefix":"10.1097","volume":"38","author":[{"given":"Gabriela","family":"Patten","sequence":"first","affiliation":[{"name":"Centre for Infectious Disease Epidemiology & Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Schomaker","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Epidemiology & Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary-Ann","family":"Davies","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Epidemiology & Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Rabie","sequence":"additional","affiliation":[{"name":"Tygerberg Academic Hospital, University of Stellenbosch, Tygerberg, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gert","family":"van Zyl","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Stellenbosch University and National Health Laboratory Service, Tygerberg, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Technau","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, University of the Witwatersrand, Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Eley","sequence":"additional","affiliation":[{"name":"Red Cross War Memorial Children\u2019s Hospital, and the Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Boulle","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Epidemiology & Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell B.","family":"Van Dyke","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Tulane University, School of Medicine, New Orleans, LA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunjal","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Centre for Biostatistics in AIDS Research (CBAR), Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nosisa","family":"Sipambo","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, University of the Witwatersrand, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Wood","sequence":"additional","affiliation":[{"name":"The Desmond Tutu HIV Centre, Institute for Infectious Disease & Molecular Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Tanser","sequence":"additional","affiliation":[{"name":"Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Mtubatuba, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Giddy","sequence":"additional","affiliation":[{"name":"McCord Hospital, Durban, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Cotton","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health Division of Paediatric Infectious Diseases, Stellenbosch University and Tygerberg Children\u2019s Hospital, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Nuttall","sequence":"additional","affiliation":[{"name":"Red Cross War Memorial Children\u2019s Hospital, and the Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gadija","family":"Essack","sequence":"additional","affiliation":[{"name":"Tygerberg Academic Hospital, University of Stellenbosch, Tygerberg, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brad","family":"Karalius","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Centre for Biostatistics in AIDS Research (CBAR), Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Seage","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Centre for Biostatistics in AIDS Research (CBAR), Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shobna","family":"Sawry","sequence":"additional","affiliation":[{"name":"Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Egger","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Epidemiology & Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee","family":"Fairlie","sequence":"additional","affiliation":[{"name":"Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R2-20230912","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1097\/QAI.0b013e3182060610","article-title":"Virologic failure and second-line antiretroviral therapy in children in South Africa\u2014the IeDEA Southern Africa collaboration.","volume":"56","author":"Davies","year":"2011","journal-title":"J Acquir Immune Defic Syndr"},{"key":"R3-20230912","first-page":"58","article-title":"Psychosocial functioning of children with AIDS and HIV infection: review of the literature from a socioecological framework.","volume":"28","author":"Steele","year":"2007","journal-title":"J Dev Behav Pediatr"},{"key":"R4-20230912","doi-asserted-by":"crossref","first-page":"18579","DOI":"10.7448\/IAS.16.1.18579","article-title":"Antiretroviral treatment, management challenges and outcomes in perinatally HIV-infected adolescents.","volume":"16","author":"Agwu","year":"2013","journal-title":"J Int AIDS Soc"},{"key":"R5-20230912","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1097\/QAD.0b013e32830f97e2","article-title":"Long-term consequences of the delay between virologic failure of highly active antiretroviral therapy and regimen modification.","volume":"22","author":"Petersen","year":"2008","journal-title":"AIDS"},{"key":"R7-20230912","doi-asserted-by":"crossref","first-page":"e199","DOI":"10.1097\/INF.0000000000001156","article-title":"Lamivudine monotherapy: experience of medium-term outcomes in HIV-infected children unable to adhere to triple therapy.","volume":"35","author":"Linder","year":"2016","journal-title":"Pediatr Infect Dis J"},{"key":"R8-20230912","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1097\/QAI.0b013e3181bef889","article-title":"Prior therapy influences the efficacy of lamivudine monotherapy in patients with lamivudine-resistant HIV-1 infection.","volume":"54","author":"Opravil","year":"2010","journal-title":"J Acquir Immune Defic Syndr"},{"key":"R9-20230912","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/jmv.21085","article-title":"HIV-1 replication capacity and genotype changes in patients undergoing treatment interruption or lamivudine monotherapy.","volume":"80","author":"Gianotti","year":"2008","journal-title":"J Med Virol"},{"key":"R10-20230912","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/QAI.0b013e318218e068","article-title":"CD4+ lymphocyte-based immunologic outcomes of perinatally HIV-infected children during antiretroviral therapy interruption.","volume":"57","author":"Siberry","year":"2011","journal-title":"J Acquir Immune Defic Syndr"},{"key":"R11-20230912","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1097\/QAD.0000000000000809","article-title":"CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States.","volume":"29","author":"Fairlie","year":"2015","journal-title":"AIDS"},{"key":"R12-20230912","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1093\/ije\/dyr080","article-title":"Cohort profile: the international epidemiological databases to evaluate AIDS (IeDEA) in sub-Saharan Africa.","volume":"41","author":"Egger","year":"2012","journal-title":"Int J Epidemiol"},{"key":"R14-20230912","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1097\/QAI.0b013e3181642257","article-title":"Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis.","volume":"47","author":"Ren","year":"2008","journal-title":"J Acquir Immune Defic Syndr"},{"key":"R15-20230912","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/QAD.0b013e3282f2be1d","article-title":"Pharmacokinetics, safety and efficacy of lopinavir\/ritonavir in infants less than 6 months of age: 24 week results.","volume":"22","author":"Chadwick","year":"2008","journal-title":"AIDS"},{"key":"R16-20230912","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1097\/00001648-200009000-00012","article-title":"Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men.","volume":"11","author":"Hern\u00e1n","year":"2000","journal-title":"Epidemiology"},{"key":"R17-20230912","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1093\/aje\/kwn164","article-title":"Constructing inverse probability weights for marginal structural models.","volume":"168","author":"Cole","year":"2008","journal-title":"Am J Epidemiol"},{"key":"R18-20230912","first-page":"382","article-title":"Bayesian model averaging: a tutorial.","volume":"14","author":"Hoeting","year":"1999","journal-title":"Stat Sci"},{"key":"R19-20230912","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S1473-3099(10)70313-3","article-title":"First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2\/3 trial.","volume":"11","author":"Babiker","year":"2011","journal-title":"Lancet Infect Dis"},{"key":"R20-20230912","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/1758-2652-14-55","article-title":"It is time to consider third-line options in antiretroviral-experienced paediatric patients?","volume":"14","author":"Zyl","year":"2011","journal-title":"J Int AIDS Soc"},{"key":"R21-20230912","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1097\/01.aids.0000218542.08845.b2","article-title":"Lamivudine monotherapy in HIV-1-infected patients harbouring a lamivudine-resistant virus: a randomized pilot study (E-184V study).","volume":"20","author":"Castagna","year":"2006","journal-title":"AIDS"},{"key":"R23-20230912","doi-asserted-by":"crossref","first-page":"19763","DOI":"10.7448\/IAS.17.4.19763","article-title":"Lamivudine monotherapy as a safe option for HIV-infected paediatric clients with adherence challenges: new evidence from a large South African cohort.","volume":"17","author":"Linder","year":"2014","journal-title":"J Int AIDS Soc"},{"key":"R25-20230912","doi-asserted-by":"crossref","first-page":"e513","DOI":"10.1542\/peds.2007-1086","article-title":"Clinical outcomes after an unstructured treatment interruption in children and adolescents with perinatally acquired HIV infection.","volume":"121","author":"Saitoh","year":"2008","journal-title":"Pediatrics"},{"key":"R26-20230912","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1097\/QAD.0b013e328333d343","article-title":"Paediatric European Network for Treatment of A. Response to planned treatment interruptions in HIV infection varies across childhood.","volume":"24","year":"2010","journal-title":"AIDS"},{"key":"R27-20230912","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1097\/01.inf.0000122601.62358.74","article-title":"Immunologic changes during unplanned treatment interruptions of highly active antiretroviral therapy in children with human immunodeficiency virus type 1 infection.","volume":"23","author":"Gibb","year":"2004","journal-title":"Pediatr Infect Dis J"},{"key":"R28-20230912","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1016\/S0140-6736(13)61409-9","article-title":"Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial.","volume":"382","author":"Cotton","year":"2013","journal-title":"Lancet"}],"container-title":["Pediatric Infectious Disease Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/00006454-201904000-00013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T18:32:48Z","timestamp":1694543568000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/00006454-201904000-00013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.1097\/inf.0000000000002156","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.733749325.793561586","asserted-by":"object"}]},"ISSN":["0891-3668"],"issn-type":[{"value":"0891-3668","type":"print"}],"subject":[],"published":{"date-parts":[[2019,4]]}}}