title: Consequences of prior use of full-dose ritonavir as single protease inhibitor as part of combination antiretroviral regimens on the future therapy choices in HIV-1-infected children.
abstract: BACKGROUND
  South African HIV-infected infants below age 6 months and children younger than 3 years on concomitant antimycobacterial treatment received full-dose ritonavir single protease inhibitor (RTV-sPI), together with 2 nucleoside reverse transcriptase inhibitors, from 2004 until 2008. Use of RTV-sPI has been described as a risk factor for PI drug resistance, but the extent of this resistance is unknown.
  
  
  OBJECTIVE
  This research assesses clinical and virological outcome of a pediatric RTV-sPI cohort at a large South African antiretroviral therapy (ART) site in a high-burden tuberculosis setting, including resistance mutations in those failing ART.
  
  
  METHODS
  All children initiated at Kalafong hospital before December 2008, who ever received RTV-sPI-based regimens, were assessed for patient outcome, virological failure and drug resistance. HIV viral loads were done 6-monthly and HIV genotyping since 2009.
  
  
  RESULTS
  There were 178 children who ever received RTV-sPI, with a mean age at ART initiation of 1.4 years. Of the 135 children (76%) with >6 months follow-up, 17 children (13%) never had viral suppression, whereas another 25 (18%) developed virological failure later. Nineteen of 26 children (73%) with genotypic resistance results had major PI mutations.
  
  
  CONCLUSIONS
  Treatment failure is not a universal feature in children with prior exposure to RTV-sPI regimens, but the significant proportion (31%) with virological failure is of concern due to high prevalence of major PI- and multiclass mutations. These children currently have no treatment options in the South African public sector, highlighting the urgent need for access to alternative ART regimens to ensure improved outcomes.
authors: From the *Department of Paediatrics, Kalafong Hospital; †Department of Family Medicine; ‡Department of Immunology, University of Pretoria, Pretoria, South Africa; §Department of Pediatrics, Yale University, New Haven, CT; and ¶Department of Paediatrics and Child Health, University of Stellenbosch, Tygerberg, South Africa.
authors: Ute D
authors: UD
authors: Feucht
authors: Theresa
authors: T
authors: Rossouw
authors: Gisela
authors: G
authors: Van Dyk
authors: Brian
authors: B
authors: Forsyth
authors: Mariana
authors: M
authors: Kruger
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000382:microbiology / Q000821:virology*; D015497:HIV-1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011480:Protease Inhibitors / Q000008:administration & dosage*; D019438:Ritonavir / Q000008:administration & dosage*; D017211:Treatment Failure; D014376:Tuberculosis / Q000188:drug therapy / Q000821:virology
chemical_list: D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D019438:Ritonavir