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In particular, World Health Organization (<jats:styled-content style=\"fixed-case\">WHO<\/jats:styled-content>) 2017 guidelines on advanced <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> disease noted that &gt;80% of children aged &lt;5\u00a0years started <jats:styled-content style=\"fixed-case\">cART<\/jats:styled-content> with <jats:styled-content style=\"fixed-case\">WHO<\/jats:styled-content> Stage 3 or 4 disease or severe immune suppression. We compared temporal trends in <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4 measures at <jats:styled-content style=\"fixed-case\">cART<\/jats:styled-content> start in children from low\u2010, middle\u2010 and high\u2010income countries, and examined the effect of <jats:styled-content style=\"fixed-case\">WHO<\/jats:styled-content> treatment initiation guidelines on reducing the proportion of children initiating <jats:styled-content style=\"fixed-case\">cART<\/jats:styled-content> with advanced disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included children aged &lt;16\u00a0years from the International Epidemiology Databases to Evaluate acquired immunodeficiency syndrome (<jats:styled-content style=\"fixed-case\">AIDS<\/jats:styled-content>) (Ie<jats:styled-content style=\"fixed-case\">DEA<\/jats:styled-content>) Collaboration (Caribbean, Central and South America, Asia\u2010Pacific, and West, Central, East and Southern Africa), the Collaboration of Observational <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> Epidemiological Research in Europe (<jats:styled-content style=\"fixed-case\">COHERE<\/jats:styled-content>), the North American Pediatric <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">AIDS<\/jats:styled-content> Cohort Study (<jats:styled-content style=\"fixed-case\">PHACS<\/jats:styled-content>) and International Maternal Pediatric Adolescent <jats:styled-content style=\"fixed-case\">AIDS<\/jats:styled-content> Clinical Trials (<jats:styled-content style=\"fixed-case\">IMPAACT<\/jats:styled-content>) 219C study. Severe immunodeficiency was defined using <jats:styled-content style=\"fixed-case\">WHO<\/jats:styled-content> guidelines. We used generalized weighted additive mixed effect models to analyse temporal trends in <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4 measurements and piecewise regression to examine the impact of 2006 and 2010 <jats:styled-content style=\"fixed-case\">WHO cART<\/jats:styled-content> initiation guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 52,153 children from fourteen low\u2010, eight lower middle\u2010, five upper middle\u2010 and five high\u2010income countries. From 2004 to 2013, the estimated percentage of children starting <jats:styled-content style=\"fixed-case\">cART<\/jats:styled-content> with severe immunodeficiency declined from 70% to 42% (low\u2010income), 67% to 64% (lower middle\u2010income) and 61% to 43% (upper middle\u2010income countries). In high\u2010income countries, severe immunodeficiency at <jats:styled-content style=\"fixed-case\">cART<\/jats:styled-content> initiation declined from 45% (1996) to 14% (2012). There were annual decreases in the percentage of children with severe immunodeficiency at <jats:styled-content style=\"fixed-case\">cART<\/jats:styled-content> initiation after the <jats:styled-content style=\"fixed-case\">WHO<\/jats:styled-content> guidelines revisions in 2006 (low\u2010, lower middle\u2010 and upper middle\u2010income countries) and 2010 (all countries).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>By 2013, less than half of children initiating <jats:styled-content style=\"fixed-case\">cART<\/jats:styled-content> had severe immunodeficiency worldwide. <jats:styled-content style=\"fixed-case\">WHO<\/jats:styled-content> treatment initiation guidelines have contributed to reducing the proportion of children and adolescents starting cART with advanced disease. However, considerable global inequity remains, in 2013, &gt;40% of children in low\u2010 and middle\u2010income countries started cART with severe immunodeficiency compared to &lt;20% in high\u2010income countries.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25200","type":"journal-article","created":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T07:20:42Z","timestamp":1543821642000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Global temporal changes in the proportion of children with advanced disease at the start of combination antiretroviral therapy in an era of changing criteria for treatment initiation"],"prefix":"10.1002","volume":"21","author":[{"given":"Klea","family":"Panayidou","sequence":"first","affiliation":[{"name":"Institute of Social and Preventive Medicine University of Bern Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8496-6475","authenticated-orcid":false,"given":"Mary\u2010Ann","family":"Davies","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Epidemiology and Research School of Public Health and Family Medicine University of Cape Town Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanina","family":"Anderegg","sequence":"additional","affiliation":[{"name":"Institute of Social and Preventive Medicine University of Bern Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7462-5132","authenticated-orcid":false,"given":"Matthias","family":"Egger","sequence":"additional","affiliation":[{"name":"Institute of Social and Preventive Medicine University of Bern Bern Switzerland"},{"name":"Centre for Infectious Disease Epidemiology and Research School of Public Health and Family Medicine University of Cape Town Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"The IeDEA, COHERE, PHACS and IMPAACT 219C Collaborations Writing Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,22]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"WHO.Antiretroviral therapy of HIV infection in infants and children: towards universal access.2006[cited 2007 Feb 09]. 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