title: Pediatric response to second-line antiretroviral therapy in South Africa.
abstract: BACKGROUND
  With improved access to pediatric antiretroviral therapy (ART) in resource-limited settings, more children could experience first-line ART treatment failure.
  
  
  METHODS
  We performed a retrospective cohort analysis using electronic medical records from HIV-infected children who initiated ART at McCord Hospital's Sinikithemba Clinic in KwaZulu-Natal, South Africa, from August 2003 to December 2010. We analyzed all records from children who began second-line ART due to first-line treatment failure. We used logistic regression to compare viral outcomes in Protease Inhibitor (PI)-based versus Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-based second-line ART, controlling for time on first-line ART, sex, and whether HIV genotyping guided the regimen change.
  
  
  RESULTS
  Of the 880 children who initiated ART during this time period, 80 (9.1%) switched to second-line ART due to therapeutic failure of first-line ART after a median of 95 weeks (IQR 65-147 weeks). Eight (10%) of the failures received NNRTI-based second-line ART, all of whom failed a PI-based first-line regimen. Seventy (87.5%) received PI-based second-line ART, all of whom failed a NNRTI-based first-line regimen. Two children (2.5%) received non-standard dual therapy as second-line ART. Six months after switching ART regimens, the viral suppression rate was significantly higher in the PI group (82%) than in the NNRTI group (29%; p=0.003). Forty-one children (51%) were tested for genotypic resistance prior to switching to second-line ART. There was no significant difference in six month viral suppression (p=0.38) between children with and without genotype testing.
  
  
  CONCLUSIONS
  NNRTI-based second-line ART carries a high risk of virologic failure compared to PI-based second-line ART.
authors.affiliation: The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Charlestown, Massachusetts, United States of America.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Zanoni
authors.forename: Henry
authors.initials: H
authors.lastname: Sunpath
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Feeney
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D016347:Medical Records Systems, Computerized; D015233:Models, Statistical; D011480:Protease Inhibitors / Q000494:pharmacology; D012044:Regression Analysis; D012189:Retrospective Studies; D013019:South Africa; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D011480:Protease Inhibitors