title: Virologic and immunologic outcomes of HIV-infected Ugandan children randomized to lopinavir/ritonavir or nonnucleoside reverse transcriptase inhibitor therapy.
abstract: BACKGROUND
  In the Prevention of Malaria and HIV disease in Tororo pediatrics trial, HIV-infected Ugandan children randomized to receive lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) experienced a lower incidence of malaria compared with children receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Here we present the results of the noninferiority analysis of virologic efficacy and comparison of immunologic outcomes.
  
  
  METHODS
  ART-naive or -experienced (HIV RNA <400 copies/mL) children aged 2 months to 6 years received either LPV/r or NNRTI-based ART. The proportion of children with virologic suppression (HIV RNA <400 copies/mL) at 48 weeks was compared using a prespecified noninferiority margin of -11% in per-protocol analysis. Time to virologic failure by 96 weeks, change in CD4 counts and percentages, and incidence of adverse event rates were also compared.
  
  
  RESULTS
  Of 185 children enrolled, 91 initiated LPV/r and 92 initiated NNRTI-based ART. At baseline, the median age was 3.1 years (range, 0.4-5.9), and 131 (71%) children were ART-naive. The proportion of children with virologic suppression at 48 weeks was 80% (67/84) in the LPV/r arm vs. 76% (59/78) in the NNRTI arm, a difference of 4% (95% confidence interval: -9% to +17%). Time to virologic failure, CD4 changes, and the incidence of Division of AIDS grade III/IV adverse events were similar between arms.
  
  
  CONCLUSIONS
  LPV/r-based ART was not associated with worse virologic efficacy, immunologic efficacy, or adverse event rates compared with NNRTI-based ART. Considering these results and the reduction in malaria incidence associated with LPV/r previously reported for this trial, wider use of LPV/r to treat HIV-infected African children in similar malaria-endemic settings could be considered.
authors: *Department of Pediatrics, University of California, San Francisco, CA; †Infectious Diseases Research Collaboration, Kampala, Uganda; ‡Department of Medicine, University of California, San Francisco, San Francisco, CA; and Departments of §Medicine; ‖Pediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda.
authors: Theodore D
authors: TD
authors: Ruel
authors: Abel
authors: A
authors: Kakuru
authors: Gloria
authors: G
authors: Ikilezi
authors: Florence
authors: F
authors: Mwangwa
authors: Grant
authors: G
authors: Dorsey
authors: Philip J
authors: PJ
authors: Rosenthal
authors: Edwin
authors: E
authors: Charlebois
authors: Diane
authors: D
authors: Havlir
authors: Moses
authors: M
authors: Kamya
authors: Jane
authors: J
authors: Achan
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007223:Infant; D061466:Lopinavir / Q000009:adverse effects / Q000627:therapeutic use*; D008288:Malaria / Q000517:prevention & control; D008297:Male; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014454:Uganda; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019438:Ritonavir