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We assessed treatment-na\u00efve children for differences in time to treatment disruption across randomly-assigned protease inhibitor versus non-nucleoside reverse transcriptase inhibitor-based initial antiretroviral therapy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We performed a secondary analysis of a multicenter phase 2\/3, randomized, open-label trial in Europe, North and South America from 2002 to 2009. Children aged 31 days to &lt;18 years, who were living with HIV-1 and treatment-naive, were randomized to antiretroviral therapy with two nucleoside reverse transcriptase inhibitors plus a protease inhibitor or non-nucleoside reverse transcriptase inhibitor. Time to first documented treatment disruption to any component of antiretroviral therapy, derived from treatment records and adherence questionnaires, was analyzed using Kaplan-Meier estimators and Cox proportional hazards models.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The modified intention-to-treat analysis included 263 participants. Seventy-two percent (<jats:italic>n =<\/jats:italic> 190) of participants experienced at least one treatment disruption during study. At 4 years, treatment disruption probabilities were 70% (protease inhibitor) vs. 63% (non-nucleoside reverse transcriptase inhibitor). The unadjusted hazard ratio (HR) for treatment disruptions comparing protease inhibitor vs. non-nucleoside reverse transcriptase inhibitor-based regimens was 1.19, 95% confidence interval [CI] 0.88\u20131.61 (adjusted HR 1.24, 95% CI 0.91\u20131.68). By study end, treatment disruption probabilities converged (protease inhibitor 81%, non-nucleoside reverse transcriptase inhibitor 84%) with unadjusted HR 1.11, 95% CI 0.84\u20131.48 (adjusted HR 1.13, 95% CI 0.84\u20131.50). Reported reasons for treatment disruptions suggested that participants on protease inhibitors experienced greater tolerability problems.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Children had similar time to treatment disruption for initial protease inhibitor and non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy, despite greater reported tolerability problems with protease inhibitor regimens. Initial pediatric antiretroviral therapy with either a protease inhibitor or non-nucleoside reverse transcriptase inhibitor may be acceptable for maintaining optimal, continuous therapy.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0242405","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T19:02:14Z","timestamp":1606158134000},"page":"e0242405","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Time to treatment disruption in children with HIV-1 randomized to initial antiretroviral therapy with protease inhibitors versus non-nucleoside reverse transcriptase inhibitors"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8599-1004","authenticated-orcid":true,"given":"Dwight 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Int J STD AIDS"},{"issue":"12","key":"pone.0242405.ref059","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1586\/eri.10.129","article-title":"Optimizing antiretroviral therapy in adolescents with perinatally acquired HIV-1 infection","volume":"8","author":"C Foster","year":"2010","journal-title":"Expert Rev Anti Infect Ther"},{"issue":"12","key":"pone.0242405.ref060","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1097\/QAD.0000000000002301","article-title":"Nonadherence and unsuppressed viral load across adolescence among US youth with perinatally acquired HIV","volume":"33","author":"D Kacanek","year":"2019","journal-title":"AIDS"},{"issue":"7","key":"pone.0242405.ref061","doi-asserted-by":"crossref","first-page":"579","DOI":"10.3851\/IMP3054","article-title":"Acceptability of lopinavir\/r pellets (minitabs), tablets and syrups in HIV-infected children","volume":"21","author":"A Kekitiinwa","year":"2016","journal-title":"Antivir Ther."},{"issue":"12","key":"pone.0242405.ref062","doi-asserted-by":"crossref","first-page":"e25214","DOI":"10.1002\/jia2.25214","article-title":"Assessing the adoption of lopinavir\/ritonavir oral pellets for HIV-positive children in Zimbabwe.","volume":"21","author":"B Pasipanodya","year":"2018","journal-title":"J Int AIDS Soc"},{"issue":"8","key":"pone.0242405.ref063","doi-asserted-by":"crossref","first-page":"e0220408","DOI":"10.1371\/journal.pone.0220408","article-title":"Understanding acceptance of and adherence to a new formulation of paediatric antiretroviral treatment in the form of pellets (LPV\/r)-A realist evaluation","volume":"14","author":"AN Giralt","year":"2019","journal-title":"PLoS One"},{"key":"pone.0242405.ref064","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jconrel.2016.02.001","article-title":"Development and in vivo evaluation of child-friendly lopinavir\/ritonavir pediatric granules utilizing novel in situ self-assembly nanoparticles","volume":"226","author":"K Pham","year":"2016","journal-title":"J Control Release"},{"issue":"10","key":"pone.0242405.ref065","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1016\/j.clinthera.2017.08.012","article-title":"Use of Adult Sensory Panel to Study Individual Differences in the Palatability of a Pediatric HIV Treatment Drug","volume":"39","author":"JA Mennella","year":"2017","journal-title":"Clin Ther"},{"issue":"9692","key":"pone.0242405.ref066","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/S0140-6736(09)60918-1","article-title":"Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial","volume":"374","author":"JL Lennox","year":"2009","journal-title":"Lancet"},{"issue":"4","key":"pone.0242405.ref067","doi-asserted-by":"crossref","first-page":"19490","DOI":"10.7448\/IAS.17.4.19490","article-title":"Once-daily dolutegravir is superior to once-daily darunavir\/ritonavir in treatment-naive HIV-1-positive individuals: 96 week results from","volume":"17","author":"JM Molina","year":"2014","journal-title":"FLAMINGO. J Int AIDS Soc"},{"issue":"1","key":"pone.0242405.ref068","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1186\/s12879-019-3975-6","article-title":"Comparative efficacy and safety of dolutegravir relative to common core agents in treatment-naive patients infected with HIV-1: a systematic review and network meta-analysis","volume":"19","author":"SJ Snedecor","year":"2019","journal-title":"BMC Infect Dis"},{"key":"pone.0242405.ref069","unstructured":"Panel on Antiretrviral Therapy and Medical Management of Children Living with HIV. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection [cited 2019 Nov 27]. Available from: http:\/\/aidsinfo.nih.gov\/contentfiles\/lvguidelines\/pediatricguidelines.pdf."},{"issue":"10","key":"pone.0242405.ref070","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1001\/jama.2010.1278","article-title":"Reuse of nevirapine in exposed HIV-infected children after protease inhibitor-based viral suppression: a randomized controlled trial","volume":"304","author":"A Coovadia","year":"2010","journal-title":"JAMA"},{"issue":"25","key":"pone.0242405.ref071","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1056\/NEJMoa1113249","article-title":"Nevirapine versus ritonavir-boosted lopinavir for HIV-infected children","volume":"366","author":"A Violari","year":"2012","journal-title":"N Engl J Med"},{"issue":"5","key":"pone.0242405.ref072","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1097\/QAI.0000000000000071","article-title":"Virologic and immunologic outcomes of HIV-infected Ugandan children randomized to lopinavir\/ritonavir or nonnucleoside reverse transcriptase inhibitor therap","volume":"65","author":"TD Ruel","year":"2014","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"8","key":"pone.0242405.ref073","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1093\/cid\/ciw488","article-title":"Nevirapine- Versus Lopinavir\/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial","volume":"63","author":"L Barlow-Mosha","year":"2016","journal-title":"Clin Infect Dis"},{"issue":"3","key":"pone.0242405.ref074","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1093\/cid\/cix335","article-title":"Switching to Efavirenz Versus Remaining on Ritonavir-boosted Lopinavir in Human Immunodeficiency Virus-infected Children Exposed to Nevirapine: Long-term Outcomes of a Randomized Trial","volume":"65","author":"PM Murnane","year":"2017","journal-title":"Clin Infect Dis"},{"issue":"Suppl 1","key":"pone.0242405.ref075","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s10461-009-9546-x","article-title":"Longitudinal antiretroviral adherence in HIV+ Ugandan parents and their children initiating HAART in the MTCT-Plus family treatment model: role of depression in declining adherence over time","volume":"13","author":"J Byakika-Tusiime","year":"2009","journal-title":"AIDS Behav"},{"issue":"17","key":"pone.0242405.ref076","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1517\/14656560903376178","article-title":"The changing pattern of adherence to antiretroviral therapy assessed at two time points, 12 months apart, in a cohort of HIV-infected children","volume":"10","author":"A Giannattasio","year":"2009","journal-title":"Expert Opin Pharmacother"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0242405","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T19:03:56Z","timestamp":1606158236000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0242405"}},"subtitle":[],"editor":[{"given":"Patricia Evelyn","family":"Fast","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,11,23]]},"references-count":76,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0242405","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,23]]}}}