title: Short communication: high rates of thymidine analogue mutations and dual-class resistance among HIV-infected Ugandan children failing first-line antiretroviral therapy.
abstract: HIV-infected children are at high risk of acquiring drug-resistant viruses, which is of particular concern in settings where antiretroviral drug options are limited. We aimed to assess resistance patterns and predict viral drug susceptibility among children with first-line antiretroviral therapy (ART) failure in Uganda. A cross-sectional analysis of children switching ART regimens due to first-line failure was performed at three clinical sites in Uganda. HIV-RNA determination and genotypic resistance testing on all specimens with HIV-RNA >1,000 copies/ml were performed. Major drug resistance mutations were scored using the 2011 International Antiviral Society-USA list. The Stanford algorithm was used to predict drug susceptibility. At the time of switch, 44 genotypic resistance tests were available for 50 children. All children harbored virus with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance [95% confidence interval (CI) 92-100%] and NRTI resistance was present in 98% (95% CI 88-100%). Forty-six percent (95% CI 30-61%) of children harbored ≥2 thymidine analog mutations. M184V was identified as the only NRTI mutation in 27% (95% CI 15-43%). HIV susceptibility to NRTIs, with the exception of tenofovir, was reduced in ≥60% of children. Ugandan children experiencing first-line ART failure in our study harbored high rates of dual-class and accumulated HIV drug resistance. Methods to prevent treatment failure, including adequate pediatric formulations and alternative second-line treatment options, are urgently needed.
authors.affiliation: PharmAccess Foundation, Amsterdam, The Netherlands. k.sigaloff@aighd.org
authors.forename: Kim C E
authors.initials: KC
authors.lastname: Sigaloff
authors.forename: Joshua
authors.initials: J
authors.lastname: Kayiwa
authors.forename: Victor
authors.initials: V
authors.lastname: Musiime
authors.forename: Job C J
authors.initials: JC
authors.lastname: Calis
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kaudha
authors.forename: Andrew
authors.initials: A
authors.lastname: Mukuye
authors.forename: Christine
authors.initials: C
authors.lastname: Matama
authors.forename: Immaculate
authors.initials: I
authors.lastname: Nankya
authors.forename: Lillian
authors.initials: L
authors.lastname: Nakatudde
authors.forename: John T
authors.initials: JT
authors.lastname: Dekker
authors.forename: Raph L
authors.initials: RL
authors.lastname: Hamers
authors.forename: Peter
authors.initials: P
authors.lastname: Mugyenyi
authors.forename: Tobias F
authors.initials: TF
authors.lastname: Rinke De Wit
authors.forename: Cissy
authors.initials: C
authors.lastname: Kityo
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D013936:Thymidine; D017211:Treatment Failure; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load / Q000187:drug effects / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D013936:Thymidine