title: Reuse of nevirapine in exposed HIV-infected children after protease inhibitor-based viral suppression: a randomized controlled trial.
abstract: BACKGROUND
  Protease inhibitor (PI)-based therapy is recommended for infants infected with human immunodeficiency virus (HIV) who were exposed to nevirapine for prevention of mother-to-child HIV transmission. However, there are limitations of continuing PI-based therapy indefinitely and reuse of nevirapine has many advantages.
  
  
  OBJECTIVE
  To test whether nevirapine-exposed infants who initially achieve viral suppression with PI-based therapy can maintain viral suppression when switched to nevirapine-based therapy.
  
  
  METHODS
  Randomized trial conducted between April 2005 and May 2009 at a hospital in Johannesburg, South Africa, among 195 children who achieved viral suppression less than 400 copies/mL for 3 or more months from a cohort of 323 nevirapine-exposed children who initiated PI-based therapy before 24 months of age.
  
  
  METHODS
  Control group children continued to receive ritonavir-boosted lopinavir, stavudine, and lamivudine (n = 99). Switch group children substituted nevirapine for ritonavir-boosted lopinavir (n = 96).
  
  
  METHODS
  Children were followed up for 52 weeks after randomization. Plasma HIV-1 RNA of greater than 50 copies/mL was the primary end point. Confirmed viremia greater than 1000 copies/mL was used as a criterion to consider regimen changes for children in either group (safety end point).
  
  
  RESULTS
  Plasma viremia greater than 50 copies/mL occurred less frequently in the switch group (Kaplan-Meier probability, 0.438; 95% CI, 0.334-0.537) than in the control group (0.576; 95% CI, 0.470-0.668) (P = .02). Confirmed viremia greater than 1000 copies/mL occurred more frequently in the switch group (0.201; 95% CI, 0.125-0.289) than in the control group (0.022; 95% CI, 0.004-0.069) (P < .001). CD4 cell response was better in the switch group (median CD4 percentage at 52 weeks, 34.7) vs the control group (CD4 percentage, 31.3) (P = .004). Older age (relative hazard [RH], 1.71; 95% CI, 1.08-2.72) was associated with viremia greater than 50 copies/mL in the control group. Inadequate adherence (RH, 4.14; 95% CI, 1.18-14.57) and drug resistance (RH, 4.04; 95% CI, 1.40-11.65) before treatment were associated with confirmed viremia greater than 1000 copies/mL in the switch group.
  
  
  CONCLUSIONS
  Among HIV-infected children previously exposed to nevirapine, switching to nevirapine-based therapy after achieving viral suppression with a ritonavir-boosted lopinavir regimen resulted in lower rates of viremia greater than 50 copies/mL than maintaining the primary ritonavir-boosted lopinavir regimen.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00117728.
authors.affiliation: Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Coovadia
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Abrams
authors.forename: Renate
authors.initials: R
authors.lastname: Stehlau
authors.forename: Tammy
authors.initials: T
authors.lastname: Meyers
authors.forename: Leigh
authors.initials: L
authors.lastname: Martens
authors.forename: Gayle
authors.initials: G
authors.lastname: Sherman
authors.forename: Gillian
authors.initials: G
authors.lastname: Hunt
authors.forename: Chih-Chi
authors.initials: CC
authors.lastname: Hu
authors.forename: Wei-Yann
authors.initials: WY
authors.lastname: Tsai
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Louise
authors.initials: L
authors.lastname: Kuhn
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D019259:Lamivudine / Q000627:therapeutic use; D061466:Lopinavir; D008297:Male; D018811:Maternal Exposure; D019829:Nevirapine / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D018119:Stavudine / Q000627:therapeutic use; D016896:Treatment Outcome; D014766:Viremia
chemical_list: D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine
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