title: High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic: A cross-sectional study.
abstract: A large cohort of 220 HIV-1-infected children (median [range] age: 12 [4-17] years) was cared and followed up in the Central African Republic, including 198 in 1st-line and 22 in 2nd-line antiretroviral regimens. Patients were monitored clinically and biologically for HIV-1 RNA load and drug resistance mutations (DRMs) genotyping. A total of 87 (40%) study children were virological responders and 133 (60%) nonresponders. In children with detectable viral load, the majority (129; 97%) represented a virological failure. In children receiving 1st-line regimens in virological failure for whom genotypic resistance test was available, 45% displayed viruses harboring at least 1 DRM to NNRTI or NRTI, and 26% showed at least 1 major DRM to NNRTI or NRTI; more than half of children in 1st-line regimens were resistant to 1st-generation NNRTI and 24% of the children in 1st-line regimens had a major DRMs to PI. Virological failure and selection of DRMs were both associated with poor adherence. These observations demonstrate high rate of virological failure after 3 to 5 years of 1st-line or 2nd-line antiretroviral treatment, which is generally associated with DRMs and therapeutic failure. Overall, more than half (55%) of children receiving 1st-line antiretroviral treatment for a median of 3.4 years showed virological failure and antiretroviral-resistance and thus eligible to 2nd-line treatment. Furthermore, two-third (64%) of children under 2nd-line therapy were eligible to 3rd-line regimen. Taken together, these observations point the necessity to monitor antiretroviral-treated children by plasma HIV-1 RNA load to diagnose as early as possible the therapeutic failure and operate switch to a new therapeutic line.
authors.affiliation: Laboratoire National de Biologie Clinique et de Santé Publique Faculté des Sciences de la Santé, Université de Bangui Complexe Pédiatrique, Bangui, Central African Republic Laboratoire de virologie, Hôpital Européen Georges Pompidou and Université Paris Descartes, Paris Sorbonne Cité, Paris, France Département des Sciences Biologiques et Centre de Recherche BioMed, Université du Québec à Montréal (UQAM), Montreal, QC, Canada Saint Georges Hospital University Medical Center, Université de Balamand, Beirut, Lebanon Unité de Recherches et d'Intervention sur les Maladies Sexuellement Transmissibles et le SIDA, Département de Santé Publique, Faculté des Sciences de la Santé de Bangui, Central African Republic Chronic Viral Illnesses Service, Division of Infectious Diseases and Research Institute of the McGill University Health Centre, Montréal Laboratoire de Bactériologie Virologie, Hôpital Aristide Le Dantec, Dakar and Université Cheikh Anta Diop de Dakar, Sénégal.
authors.forename: Christian Diamant
authors.initials: CD
authors.lastname: Mossoro-Kpinde
authors.forename: Jean-Chrysostome
authors.initials: JC
authors.lastname: Gody
authors.forename: Ralph-Sydney
authors.initials: RS
authors.lastname: Mboumba Bouassa
authors.forename: Olivia
authors.initials: O
authors.lastname: Mbitikon
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Jenabian
authors.forename: Leman
authors.initials: L
authors.lastname: Robin
authors.forename: Mathieu
authors.initials: M
authors.lastname: Matta
authors.forename: Kamal
authors.initials: K
authors.lastname: Zeitouni
authors.forename: Jean De Dieu
authors.initials: JD
authors.lastname: Longo
authors.forename: Cecilia
authors.initials: C
authors.lastname: Costiniuk
authors.forename: Gérard
authors.initials: G
authors.lastname: Grésenguet
authors.forename: Ndèye Coumba
authors.initials: NC
authors.lastname: Touré Kane
authors.forename: Laurent
authors.initials: L
authors.lastname: Bélec
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002488:Central African Republic; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015751:Genes, pol; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000151:congenital / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D055118:Medication Adherence; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral