title: Antiretroviral treatment outcome following genotyping in Thai children who failed dual nucleoside reverse transcriptase inhibitors.
abstract: OBJECTIVE
  To evaluate outcomes in dual nucleoside reverse transcriptase inhibitor (NRTI) pretreated children after genotyping (GT).
  
  
  METHODS
  We assessed CD4 and viral load (VL) in children three years after baseline GT at the time of dual NRTI failure. Baseline high grade resistance (HR) was defined as >or=4 nucleoside analogue mutations (NAMs)+/-Q151M or 69 insertion complex, and low grade resistance (LR) was defined as <4 NAMs. Genotypic susceptibility scores (GSS) were determined. The current selection of antiretrovirals (ARV) was based on physician judgment and ARV availability.
  
  
  RESULTS
  Seventy-two children were enrolled, with a mean age of 9.3 years; 61% were female. Baseline median CD4 was 18%, VL was 1.7 log(10) with HR 37.5%, LR 56.9% and no mutation (NR, no resistance) 5.6%. Sixty-five (90.3%) switched ARV: 46.2% non-nucleoside reverse transcriptase inhibitor (NNRTI), 30.8% protease inhibitor (PI), and 23.1% PI+NNRTI based highly active antiretroviral therapy (HAART). The choice of regimen did not differ based on baseline HR, LR, and NR. The median duration from dual NRTI therapy to HAART was 5.4 years (interquartile range (IQR) 4.0-6.9 years) and the mean (SD) duration of current HAART regimen was 1.51 (1.78) years; both were similar between ARV groups. Five children continued dual NRTI, two interrupted therapy. The GSS score was significantly higher in the PI group (3.1) vs. PI+NNRTI (2.5) vs. NNRTI (2.6) groups. Sixty-three percent of the HR group used PI or PI+NNRTI-based HAART compared to 41% of the LR group, p=not significant. At follow-up, median CD4 changes from baseline were +5% and VL -2.2 log(10) (p<0.001). VL <1.7 log(10) was seen in 59.3% of HR, 58.5% of LR, and 50.0% of NR groups (no significant difference). More children on PI (75%) and PI+NNRTI (80%) based HAART had VL <50 compared to NNRTI-based HAART (50%), p=0.003.
  
  
  CONCLUSIONS
  PI-based regimens showed a higher rate of undetectable VL compared with NNRTI-based regimens. Having GT may not affect second-line treatment choices in developing countries, most likely due to late VL failure and limited availability of PIs.
authors.affiliation: The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Center, Bangkok, Thailand. torsak.b@hivnat.org
authors.forename: Torsak
authors.initials: T
authors.lastname: Bunupuradah
authors.forename: Piyarat
authors.initials: P
authors.lastname: Suntarattiwong
authors.forename: Andrea
authors.initials: A
authors.lastname: Li
authors.forename: Sunee
authors.initials: S
authors.lastname: Sirivichayakul
authors.forename: Chitsanu
authors.initials: C
authors.lastname: Pancharoen
authors.forename: Pitch
authors.initials: P
authors.lastname: Boonrak
authors.forename: Thanyawee
authors.initials: T
authors.lastname: Puthanakit
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kerr
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: Tawee
authors.initials: T
authors.lastname: Chotpitayasunondh
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D002648:Child; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006678:HIV / Q000254:growth & development*; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology; D006801:Humans; D008297:Male; D010349:Patient Compliance; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013785:Thailand
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors