{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:45:21Z","timestamp":1777452321864,"version":"3.51.4"},"reference-count":15,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We examined the prevalence of ritonavir-boosted darunavir (DRV) resistance-associated mutations (RAMs) in HIV-infected children in the UK to determine the drug's potential clinical utility as a first-line or second- line protease inhibitor (PI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The prevalence of DRV RAMs, identified from IAS 2010 and Stanford, and the Stanford susceptibility score, were estimated in PI-naive and PI-experienced children in the Collaborative HIV Paediatric Study and the UK HIV Drug Resistance Database 1998\u20132008. Associations between type\/duration of PI exposure and area under the viraemia curve on PI with the number of RAMs were investigated using multivariate Poisson regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 17\/417 (4%) children with a resistance test when PI-naive had one IAS DRV RAM, and 1 had a Stanford mutation; none had multiple DRV RAMs. A total of 177 PI-experienced children had a test after a median 2.7 years (IQR 1.1\u20135.2) on PIs; 19 (11%) had one IAS DRV RAM, 7 (4%) had two RAMs, 1 (0.6%) had three RAMs and 1 (0.6%) had four RAMs. DRV RAMs were independently associated with increased years on a PI, a larger area under the viraemia curve since starting PIs, and any exposure to PIs other than lopinavir (all P\u22640.05). Only 6 (3%) PI-experienced children had intermediate-level DRV\/ritonavir resistance; none had high-level resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DRV resistance was negligible in PI-naive children and those with lopinavir PI exposure alone. However resistance increased with increasing time, and with higher levels of viraemia, on PIs. Once-daily DRV\/ritonavir would be valuable as a second PI or an alternative first PI, particularly if coformulated with a booster in an appropriate formulation for children.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp2015","type":"journal-article","created":{"date-parts":[[2011,12,15]],"date-time":"2011-12-15T11:37:51Z","timestamp":1323949071000},"page":"599-603","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["The Prevalence of Darunavir-Associated Mutations in HIV-1-Infected Children in the Uk"],"prefix":"10.1177","volume":"17","author":[{"given":"Katherine L","family":"Donegan","sequence":"first","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A Sarah","family":"Walker","sequence":"additional","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Dunn","sequence":"additional","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Judd","sequence":"additional","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deenan","family":"Pillay","sequence":"additional","affiliation":[{"name":"Research Department of Infection, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esse","family":"Menson","sequence":"additional","affiliation":[{"name":"Evelina Children's Hospital, St Thomas\u2019 NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermione","family":"Lyall","sequence":"additional","affiliation":[{"name":"Department of Medicine, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth","family":"Tudor-Williams","sequence":"additional","affiliation":[{"name":"Department of Medicine, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana M","family":"Gibb","sequence":"additional","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2011,5,1]]},"reference":[{"key":"bibr1-IMP2015","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32832d7350"},{"key":"bibr2-IMP2015","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61049-6"},{"key":"bibr3-IMP2015","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60497-8"},{"key":"bibr4-IMP2015","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328330abaa"},{"key":"bibr5-IMP2015","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1293.2009.00759.x"},{"key":"bibr6-IMP2015","unstructured":"Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection; pp. 1\u2013219. (Updated 16 August 2010. Accessed 6 December 2010.) Available from http:\/\/aidsinfo.nih.gov\/ContentFiles\/PediatricGuidelines.pdf."},{"key":"bibr7-IMP2015","unstructured":"PREZISTA\n                      \u00ae\n                      (darunavir). Summary of product characteristics. (Updated August 2010. Accessed 31 October 2010.) Available from http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Product_Information\/human\/000707\/WC500041756.pdf."},{"key":"bibr8-IMP2015","unstructured":"Violari A., Bologna R., Kimutai R. ARIEL: 24-week safety and efficacy of DRV\/r in treatment-experienced 3 to <6 year old patients.\n                      18th Conference on Retroviruses and Opportunistic Infection.\n                      27 February\u201311 March 2011, Boston, MA, USA. Poster 713."},{"key":"bibr9-IMP2015","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2007.0173"},{"issue":"3","key":"bibr10-IMP2015","first-page":"A33","volume":"13","author":"de Meyer S.","year":"2009","journal-title":"Antivir Ther"},{"key":"bibr11-IMP2015","doi-asserted-by":"crossref","unstructured":"De La Rosa G., Pattery T., Picchio G., Lathouwers E., Villacian J., Van der Borght K. Changing prevalence of darunavir resistance-associated mutations (DRV RAMs) in clinical samples received for routine resistance testing: 2003-2009.\n                      10th International Congress on Drug Therapy in HIV Infection.\n                      7\u201311 November 2010, Glasgow, UK. Poster P132.","DOI":"10.1186\/1758-2652-13-S4-P132"},{"issue":"1","key":"bibr12-IMP2015","first-page":"A147","volume":"14","author":"de Meyer S.","year":"2009","journal-title":"Antivir Ther"},{"key":"bibr13-IMP2015","doi-asserted-by":"publisher","DOI":"10.1086\/521167"},{"key":"bibr14-IMP2015","first-page":"156","volume":"18","author":"Johnson V.A.","year":"2010","journal-title":"Top HIV Med"},{"key":"bibr15-IMP2015","doi-asserted-by":"publisher","DOI":"10.1086\/432763"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP2015","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP2015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:50:39Z","timestamp":1777380639000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP2015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5,1]]},"references-count":15,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012,5]]}},"alternative-id":["10.3851\/IMP2015"],"URL":"https:\/\/doi.org\/10.3851\/imp2015","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5,1]]}}}