title: High rate of antiretroviral drug resistance mutations in HIV type 1-infected Senegalese children in virological failure on first-line treatment according to the World Health Organization guidelines.
abstract: The rates of virological failure (VF) and HIV-1 drug resistance were evaluated in a cross-sectional study in HIV-1-infected children living in Dakar, and taking antiretroviral treatment (ART) according to WHO recommendations. The plasma HIV-1 RNA load was measured using the Abbott m2000 RealTime HIV-1 assay. The full-length protease gene and partial reverse transcriptase gene were sequenced, and resistance mutations were assessed by reference to the Stanford University HIV drug resistance database. Of 125 included children (median age, 7 years) taking first-line ART for a median duration of 20 months, 82 (66%) showed detectable HIV-1 RNA load, and 70 (56%) met the 2010 revised WHO criteria of VF (defined as plasma HIV-1 RNA load ≥3.7 log(10) copies/ml). Drug resistance results were available for 52 children with plasma HIV-1 RNA load ≥3.0 log(10) copies/ml, and viruses carrying resistance mutations were found in 48 (92%) children. Among these 48, mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs) or non-NRTIs (NNRTIs) were found in 42 (88%) and 47 (99%) children, respectively. The NRTI-resistant viruses harbored the M184V/I (95%), Q151M (2%), and thymidine-analogue mutations (40%), and the NNRTI-resistant viruses harbored the K103N (34%), Y181C (32%), G190A (23%), and K101E (21%) mutations. A high rate (56%) of VF was demonstrated in Senegalese children after 20 months of first-line ART and therapeutic failure was assessed by the presence of antiretroviral drug resistance mutations in 9 out of 10 children in VF. These findings point out the difficulties of optimizing ART in children living in sub-Saharan Africa, and the crucial need of laboratory monitoring reinforcement.
authors.affiliation: Laboratoire de Bactériologie-Virologie , CHU Aristide le Dantec, Dakar, Sénégal.
authors.forename: Khady
authors.initials: K
authors.lastname: Kebe
authors.forename: Moussa
authors.initials: M
authors.lastname: Thiam
authors.forename: Ndeye Rama
authors.initials: NR
authors.lastname: Diagne Gueye
authors.forename: Halimatou
authors.initials: H
authors.lastname: Diop
authors.forename: Aïchatou
authors.initials: A
authors.lastname: Dia
authors.forename: Haby
authors.initials: H
authors.lastname: Signate Sy
authors.forename: Charlotte
authors.initials: C
authors.lastname: Charpentier
authors.forename: Laurent
authors.initials: L
authors.lastname: Belec
authors.forename: Souleymane
authors.initials: S
authors.lastname: Mboup
authors.forename: Coumba
authors.initials: C
authors.lastname: Toure Kane
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D012675:Senegal / Q000453:epidemiology; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease