1. Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV: an international cohort collaboration
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Charlotte Duff, Marcel Yotebieng, Kennedy Malisita, Mwita Lumumba, Diana M. Gibb, Kunjal Patel, Venessa Timmerman, Paige L. Williams, Patrick Oyaro, Shaffiq Essajee, Jorge Pinto, Harriet Nuwagaba-Biribonwoha, Alla Volokha, Miriam Chernoff, Makhosazana Hlatshwayo, Kulkanya Chokephaibulkit, Pablo Rojo Conejo, Patricia Lelo, Filipa Prata, Irene Marete, Colette Smith, Ruth L. Goodall, Jihane Ben-Farhat, Russell B. Van Dyke, Vanessa Rouzier, Christoph Rudin, Valériane Leroy, Lynne M. Mofenson, Claire Thorne, Rachel C. Vreeman, Luminita Ene, Liubov Okhonskaia, Sebastian Wanless, Tessa Goetghebuer, Andreas D Haas, Chloe A. Teasdale, Myron J. Levin, Geoffrey Fatti, Mary-Ann Davies, Edith Q. Mohapi, Azar Kariminia, Murli Purswani, Laura Marques, Sybil Geelen, Ellen G. Chadwick, Mary E. Paul, Nicky Maxwell, Mark J. Abzug, Rita Lyamuya, Lars Navér, Adeodata Kekitiinwa-Rukyalekere, Andrew Boulle, Peter N. Kazembe, Intira Jeannie Collins, Magdalena Marczyńska, Antoni Noguera-Julian, Andrew Edmonds, James M. Oleske, Gonzague Jourdain, Regina Célia de Menezes Succi, Marissa Vicari, Fatoumata Dicko, Suna Balkan, Linda-Gail Bekker, Elaine J. Abrams, Kara Wools-Kaloustian, Ali Judd, Carlo Giaquinto, Shirley Traite, Annette H. Sohn, Josiane Warszawski, George R. Seage, Mogomotsi Matshaba, Luisa Galli, and Sophie Desmonde
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0301 basic medicine ,Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Epidemiology ,Immunology ,Infectious Diseases ,Virology ,International Cooperation ,610 Medicine & health ,HIV Infections ,Global Health ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,360 Social problems & social services ,medicine ,Humans ,Cumulative incidence ,030212 general & internal medicine ,Child ,Proportional hazards model ,business.industry ,Drug Substitution ,Incidence (epidemiology) ,Incidence ,Infant, Newborn ,Infant ,Viral Load ,medicine.disease ,030112 virology ,CD4 Lymphocyte Count ,Regimen ,Observational Studies as Topic ,Anti-Retroviral Agents ,Child, Preschool ,Cohort ,Female ,business ,Viral load - Abstract
BACKGROUND Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. METHODS In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. FINDINGS At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6-6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0-3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5-7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6-1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p
- Published
- 2019
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