{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:00:14Z","timestamp":1790078414491,"version":"4.0.1"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>The ANRS 12174 trial assessed the efficacy and tolerance of lopinavir (LPV)-ritonavir (LPV\/r) prophylaxis versus those of lamivudine (3TC) prophylaxis administered to breastfed infants whose HIV-infected mothers were not on antiretroviral therapy. In this substudy, we assessed LPV\/r and 3TC pharmacokinetics to evaluate the percentage of infants with therapeutic plasma concentrations and to discuss these data in the context of a prophylactic treatment. Infants from the South African trial site underwent blood sampling for pharmacokinetic study at weeks 6, 26, and 38 of life. We applied a Bayesian approach to derive the 3TC and LPV pharmacokinetic parameters on the basis of previously published pharmacokinetic models for HIV-infected children. We analyzed 114 LPV and 180 3TC plasma concentrations from 69 infants and 92 infants, respectively. A total of 30 LPV and 20 3TC observations were considered missing doses and discarded from the Bayesian analysis. The overall population analysis showed that 30 to 40% of the infants did not reach therapeutic targets, regardless of treatment group. The median LPV trough concentrations at weeks 6, 26, and 38 were 2.8 mg\/liter (interquartile range [IQR], 1.7 to 4.4 mg\/liter), 5.6 mg\/liter (IQR, 3.2 to 7.7 mg\/liter), and 3.4 mg\/liter (IQR, 2.3 to 7.3 mg\/liter), respectively. The median 3TC area under the curve from 0 to 12 h after the last drug intake were 5.6 mg \u00b7 h\/liter (IQR, 4.1 to 7.8 mg \u00b7 h\/liter), 5.9 mg \u00b7 h\/liter (IQR, 5.1 to 7.5 mg \u00b7 h\/liter), and 7.3 mg \u00b7 h\/liter (IQR, 4.9 to 8.5 mg \u00b7 h\/liter) at weeks 6, 26, and 38, respectively. Use of the therapeutic doses recommended by the WHO would have resulted in a higher proportion of infants achieving the targets. However, no HIV-1 infection was reported among these infants. These results suggest that the prophylactic targets for both 3TC and LPV may be lower than the therapeutic ones. For treatment, the WHO dosing guidelines should be suitable to maintain values above the therapeutic pharmacokinetic targets in most infants. (This study has been registered at ClinicalTrials.gov under identifier NCT00640263.)<\/jats:p>","DOI":"10.1128\/aac.01869-16","type":"journal-article","created":{"date-parts":[[2016,11,29]],"date-time":"2016-11-29T02:31:07Z","timestamp":1480386667000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Are Prophylactic and Therapeutic Target Concentrations Different?: the Case of Lopinavir-Ritonavir or Lamivudine Administered to Infants for Prevention of Mother-to-Child HIV-1 Transmission during Breastfeeding"],"prefix":"10.1128","volume":"61","author":[{"given":"Frantz","family":"Foissac","sequence":"first","affiliation":[{"name":"EA7323, Pharmacology and Drugs Evaluation in Children and Pregnant Women, Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Unit\u00e9 de Recherche Clinique, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Tarnier, Paris, France"},{"name":"CIC-0901 INSERM, Cochin-Necker, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rn","family":"Blume","sequence":"additional","affiliation":[{"name":"Centre for International Health, University of Bergen, Bergen, Norway"},{"name":"Effective Care Research Unit, University of Fort Hare, East London, South Africa"},{"name":"School of Public Health, University of the Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Tr\u00e9luyer","sequence":"additional","affiliation":[{"name":"EA7323, Pharmacology and Drugs Evaluation in Children and Pregnant Women, Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Unit\u00e9 de Recherche Clinique, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Tarnier, Paris, France"},{"name":"CIC-0901 INSERM, Cochin-Necker, Paris, France"},{"name":"Service de Pharmacologie Clinique, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Cochin, Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorkild","family":"Tyllesk\u00e4r","sequence":"additional","affiliation":[{"name":"Centre for International Health, University of Bergen, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chipepo","family":"Kankasa","sequence":"additional","affiliation":[{"name":"University of Zambia, School of Medicine, Department of Pediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Meda","sequence":"additional","affiliation":[{"name":"Centre of International Research for Health, Faculty of Health Sciences, University of Ouagadougou, Ouagadougou, Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James K.","family":"Tumwine","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandisa","family":"Singata-Madliki","sequence":"additional","affiliation":[{"name":"Effective Care Research Unit, University of Fort Hare, East London, South Africa"},{"name":"School of Public Health, University of the Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Harper","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Frere Hospital and Walter Sisulu University, East London, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia M.","family":"Illamola","sequence":"additional","affiliation":[{"name":"EA7323, Pharmacology and Drugs Evaluation in Children and Pregnant Women, Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Service de Pharmacologie Clinique, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Cochin, Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na\u00efm","family":"Bouazza","sequence":"additional","affiliation":[{"name":"EA7323, Pharmacology and Drugs Evaluation in Children and Pregnant Women, Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Unit\u00e9 de Recherche Clinique, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Tarnier, Paris, France"},{"name":"CIC-0901 INSERM, Cochin-Necker, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Nagot","sequence":"additional","affiliation":[{"name":"CHU Montpellier and INSERM U1058, Montpellier, France"},{"name":"Universit\u00e9 Montpellier, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Van de Perre","sequence":"additional","affiliation":[{"name":"CHU Montpellier and INSERM U1058, Montpellier, France"},{"name":"Universit\u00e9 Montpellier, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Blanche","sequence":"additional","affiliation":[{"name":"EA7323, Pharmacology and Drugs Evaluation in Children and Pregnant Women, Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Unit\u00e9 d'Immunologie-H\u00e9matologie P\u00e9diatrique, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Necker, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9borah","family":"Hirt","sequence":"additional","affiliation":[{"name":"EA7323, Pharmacology and Drugs Evaluation in Children and Pregnant Women, Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Unit\u00e9 de Recherche Clinique, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Tarnier, Paris, France"},{"name":"CIC-0901 INSERM, Cochin-Necker, Paris, France"},{"name":"Service de Pharmacologie Clinique, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Cochin, Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"UNAIDS report on the global AIDS epidemic 2013","author":"Joint United Nations Programme on HIV\/","year":"2013","unstructured":"Joint United Nations Programme on HIV\/ AIDS. 2013. UNAIDS report on the global AIDS epidemic 2013. Joint United Nations Programme on HIV\/AIDS, Geneva, Switzerland."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD011323"},{"key":"e_1_3_3_4_2","volume-title":"Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection","author":"WHO","year":"2016","unstructured":"WHO. 2016. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. WHO, Geneva, Switzerland."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-12-246"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00984-8"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.218"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3851\/IMP3016"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32835caad1"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000000298"},{"key":"e_1_3_3_11_2","first-page":"4","article-title":"Updated guideline to perform therapeutic drug monitoring for antiretroviral agents","volume":"3","author":"Porte CJ","year":"2006","unstructured":"Porte CJ BackD BlaschkeT BoucherCAB FletcherCV FlexnerC GerberJ KashubaADM SchapiroJM BurgerDM. 2006. Updated guideline to perform therapeutic drug monitoring for antiretroviral agents. Rev Antivir Ther3:4\u201312.","journal-title":"Rev Antivir Ther"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11096-013-9861-1"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2013.812072"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0355-4"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-015-0340-9"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00126334-200312150-00006"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000135"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/515641"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200342060-00009"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3182908c00"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2008.02.005"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.915"},{"key":"e_1_3_3_23_2","unstructured":"Food and Drug Administration. 2011. FDA drug safety communication: serious health problems seen in premature babies given Kaletra (lopinavir\/ritonavir) oral solution. Food and Drug Administration Rockville MD. http:\/\/www.fda.gov\/Drugs\/DrugSafety\/ucm246002.htm#data_summary."},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2014.06.034"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01869-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01869-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:41:27Z","timestamp":1645476087000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01869-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2]]},"references-count":23,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,2]]}},"alternative-id":["10.1128\/AAC.01869-16"],"URL":"https:\/\/doi.org\/10.1128\/aac.01869-16","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2]]},"assertion":[{"value":"2016-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-11-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-01-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01869-16"}}