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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Plasma drug concentrations and virologic evaluations after stopping treatment with nonnucleoside reverse-transcriptase inhibitors in HIV type 1-infected children
Clinical Infectious Diseases, Volume 46, No. 10, Year 2008
Notification
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Description
Background. The optimum strategy for stopping treatment with drugs that have different half-lives in a combination regimen to minimize the risk of selecting drug-resistant viruses remains unknown. We evaluated drug concentrations in plasma, human immunodeficiency virus (HIV) load, and development of drug resistance after a planned treatment interruption of a nonnucleoside reverse-transcriptase inhibitor (NNRTI)-containing regimen in HIV type 1-infected children. Methods. Children with viral loads <50 copies/mL and CD4 cell percentages ≥30% (for children aged 2-6 years) or CD4 cell percentages ≥25% and CD4 cell counts ≥500 cells/μL (for children aged 7-15 years) were randomized to either a planned treatment interruption or to continuous therapy. In the planned treatment interruption arm, either (1) treatment with nevirapine or efavirenz was stopped, and treatment with the remaining drugs was continued for 7-14 days, or (2) nevirapine or efavirenz were replaced by a protease inhibitor, and all drugs were stopped after 7-14 days. Sampling for determination of plasma drug concentrations, measurement of viral load, and drug resistance testing was scheduled at day 0, day 7 (drug concentrations only), day 14, and day 28 after interruption of treatment with an NNRTI. Results. Treatment with an NNRTI was interrupted for 35 children (20 were receiving nevirapine, and 15 were receiving efavirenz). Median time from NNRTI cessation to stopping all drugs was 9 days (range, 6-15 days) for nevirapine and 14 days (range, 6-18 days) for efavirenz. At 7 days, 1 (5%) of 19 and 4 (50%) of 8 children had detectable nevirapine and efavirenz concentrations, respectively; efavirenz remained detectable in 3 (25%) of 12 children at 14 days. At 14 days, viral load was ≥50 copies/mL in 6 of 16 children interrupting treatment with nevirapine (range, 52-7000 copies/mL) and in 2 of 12 children interrupting treatment with efavirenz (range, 120-1600 copies/mL). No new NNRTI mutations were observed. Conclusions. In children with virological suppression who experienced interruption of treatment with an NNRTI, staggered or replacement stopping strategies for a median of 9 days for nevirapine and 14 days for efavirenz were not associated with the selection of NNRTI resistance mutations. © 2008 by the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Cressey, Tim R.
Thailand, Bangkok
Institute of Research for Development, Thailand
United States, Cambridge
Harvard University
Thailand, Chaing Mai
Chiang Mai University
Khoo, Saye Hock
United Kingdom, Liverpool
University of Liverpool
Tréluyer, Jean Marc
France, Paris
Hopital Saint-vincent-de-paul
Compagnucci, Alexandra
France, Paris
Inserm
Saïdi, Yacine
France, Paris
Inserm
Lallemant, Marc J.
Thailand, Bangkok
Institute of Research for Development, Thailand
United States, Cambridge
Harvard University
Gibb, Diana M.
United Kingdom, London
Mrc Clinical Trials Unit
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Burger, David M.
Netherlands, Nijmegen
Radboud University Medical Center
Aboulker, Jean Pierre
France, Paris
Inserm
Babiker, Abdel G.A.G.
United Kingdom, London
Mrc Clinical Trials Unit
Blanche, Stéphane
Unknown Affiliation
Bohlin, Ann Britt
Unknown Affiliation
Butler, Karina M.
Unknown Affiliation
Castelli-Gattinara, Guido
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Clayden, Polly
Unknown Affiliation
Darbyshire, Janet H.
United Kingdom, London
Mrc Clinical Trials Unit
Debré, Marianne A.
Unknown Affiliation
de Groot, Ronald C.A.
Unknown Affiliation
Della-Negra, Marinella
Unknown Affiliation
Giaquinto, Carlo
Italy, Padua
Università Degli Studi Di Padova
Grosch-Wörner, Ilse
Unknown Affiliation
Kind, Christian H.
Unknown Affiliation
Lévy, Jack A.
Unknown Affiliation
Lyall, Hermione
United Kingdom, London
St Mary's Hospital
United Kingdom, London
Chelsea and Westminster Hospital
Marczyńska, Magdalena
Poland, Warsaw
Medical University of Warsaw
Mellado-Peña, María José
Unknown Affiliation
Nadal, David
Unknown Affiliation
Niehues, Tim
Unknown Affiliation
Peckham, Catherine S.
Unknown Affiliation
Ramos, José Tomás
Spain, Getafe
Hospital Universitario de Getafe
Rosado, L.
Unknown Affiliation
Rudin, Christoph
Unknown Affiliation
Scherpbier, Henriëtte J.
Unknown Affiliation
Sharland, Mike R.
Unknown Affiliation
Tovo, P.
Unknown Affiliation
Tudor-Williams, Gareth
United Kingdom, London
St Mary's Hospital
Walker, Anne Sarah
United Kingdom, London
Mrc Clinical Trials Unit
Wintergerst, Uwe
Unknown Affiliation
Harper, Lynda M.
United Kingdom, London
Mrc Clinical Trials Unit
Klein, Nigel J.
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Mofenson, Lynne M.
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Moye, John
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Jacqz-Aigrain, Évelyne M.
Unknown Affiliation
Clerici, Mario S.
Unknown Affiliation
De Rossi, Anita
Unknown Affiliation
Ngo-Giang-Huong, Nicole
Unknown Affiliation
Morris, Lynn G.
United Kingdom, London
Ucl Medical School
Hill, Catherine Mary
Unknown Affiliation
Lepage, Philippe
Unknown Affiliation
Pozniak, Anton Louis
Unknown Affiliation
Vella, Stefano
Unknown Affiliation
Eliette, Véronique
France, Paris
Inserm
Léonardo, S.
France, Paris
Inserm
Riault, Yoann
France, Paris
Inserm
Farrelly, Laura
United Kingdom, London
Mrc Clinical Trials Unit
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Johnson, Debra L.
United Kingdom, London
Mrc Clinical Trials Unit
Taylor, Christopher B.
United Kingdom, London
Mrc Clinical Trials Unit
Chalermpantmetagul, Suwalai
Unknown Affiliation
Peongjakta, Rukchanok
Unknown Affiliation
Chailert, Sanuphong
Unknown Affiliation
Fregonese, Federica
Unknown Affiliation
Jourdain, Gonzague
Unknown Affiliation
Flóret, Daniel
France, Lyon
Hopital Edouard Herriot
Cottalorda, Jacqueline
France, Nice
Centre Hospitalier Universitaire de Nice, Hôpital L'archet
Lefèbvre, Jean Claude
France, Nice
Centre Hospitalier Universitaire de Nice, Hôpital L'archet
Mellul, Sandra
France, Nice
Centre Hospitalier Universitaire de Nice, Hôpital L'archet
Faye, Albert
France, Paris
Hôpital Robert-debré Ap-hp
Damond, Florence
France, Paris
Hôpital Robert-debré Ap-hp
Krivine, Anne
France, Paris
Hopital Saint-vincent-de-paul
Chaix, Marie Laure
France, Paris
Hôpital Necker Enfants Malades
Notheis, Gundula
Unknown Affiliation
Strotmann, G.
Unknown Affiliation
Schlieben, S.
Unknown Affiliation
Zanchetta, Marisa
Italy, Padua
Università Degli Studi Di Padova
Martino, Alessandra Maria
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Bernardi, Stefania
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Mazza, Antonio
Italy, Trento
Ospedale S. Chiara
Popielska, Jolanta
Poland, Warsaw
Medical University of Warsaw
Alimenti, Ariane M.
Spain, Madrid
Hospital Universitario la Paz
Navarro-Gõmez, Marisa Luisa
Spain, Madrid
Hospital General Universitario Gregorio Marañón
Munoz-Fernandez, M. A.
Spain, Madrid
Hospital General Universitario Gregorio Marañón
García Rodriguez, Marie Cruz
Spain, Madrid
Hospital Materno-infantil
Núñez Cuadros, Esmeralda
Spain, Malaga
Hospital Materno-infantil de Malaga
Asensi-Botet, Francesc
Spain, Valencia
Hospital Infantil la fe
Schüpbach, Jörg Rg
Unknown Affiliation
Bunupuradah, Torsak
Thailand, Bangkok
Hiv
Ananworanich, Jintanat
Thailand, Bangkok
Hiv
Phanuphak, Praphan
Thailand, Bangkok
Hiv
Intasan, Jintana
Thailand, Bangkok
Hiv
Kanjanavanit, Suparat
Thailand, Chaing Mai
Nakornping Hospital
Foster, Caroline J.
United Kingdom, London
St Mary's Hospital
Kaye, Steve
United Kingdom, London
St Mary's Hospital
Novelli, Vas M.
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Shingadia, Delane V.
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
United Kingdom, London
Newham University Hospital
Flynn, Jacquie
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Clapson, Margaret
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
McMaster, Paddy
United Kingdom, Stoke-on-trent
Royal Stoke University Hospital
Liebeschuetz, Susan
United Kingdom, London
Newham University Hospital
Rana, Sohail R.
United States, Washington, D.c.
Howard University Hospital
Roa, Jhoanna C.
United States, Washington, D.c.
Howard University Hospital
Puga, Ana M.
United States, Fort Lauderdale
Children's Diagnostic and Treatment Center
Regazzi, Mario B.
Italy, Pavia
Fondazione Irccs Policlinico San Matteo
Gibbons, Sara E.
United Kingdom, Liverpool
University of Liverpool
Jullien, Vincent
France, Paris
Hopital Saint-vincent-de-paul
Rey, Elisabeth
France, Paris
Hopital Saint-vincent-de-paul
Statistics
Citations: 17
Authors: 105
Affiliations: 40
Identifiers
Doi:
10.1086/587657
ISSN:
10584838
Research Areas
Infectious Diseases
Maternal And Child Health