title: Lopinavir/ritonavir monotherapy as a nucleoside analogue-sparing strategy to prevent HIV-1 mother-to-child transmission: the ANRS 135 PRIMEVA phase 2/3 randomized trial.
abstract: BACKGROUND
  Prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) is usually based on zidovudine-containing regimens, despite potential toxicities. This multicenter trial evaluated whether lopinavir/ritonavir (LPV/r) monotherapy in HIV type 1-infected women not requiring antiretrovirals for themselves could control maternal viral load (VL).
  
  
  METHODS
  Overall, 105 pregnant women with baseline VL <30 000 copies/mL and CD4 ≥350 cells/µL were randomized to start open-label LPV/r 400/100 mg twice daily alone (monotherapy group, n = 69) or combined with zidovudine/lamivudine 300/150 mg twice daily (triple therapy group, n = 36) from 26 gestational weeks to delivery. According to a Fleming 2-stage phase 2 design, monotherapy was considered to be efficacious if at least 59 patients achieved VL <200 copies/mL at 8 weeks of treatment (primary endpoint). Secondary endpoints were VL at delivery and tolerance.
  
  
  RESULTS
  Monotherapy was efficacious as defined: 62 women in the monotherapy group achieved VL <200 copies/mL at 34 weeks' gestation (ie, 8 weeks of treatment; 89.9%; 95% confidence interval [CI], 80.2%-95.8%). At delivery, proportions with VL <200 copies/mL were similar in the monotherapy and triple therapy groups (92.8% vs 97.2%; P = .66); however, fewer had VL <50 copies/mL in the monotherapy group (78.3% vs 97.2%; P = .01). Changes for intolerance were less frequent in the monotherapy than in the triple therapy group (1.4% vs 11.1%, respectively; P = .046). Cesarean delivery and preterm delivery rates did not differ. All children were liveborn; 1 case of HIV-1 transmission occurred in the triple therapy group, none in the monotherapy group (95% CI upper limit = 5.2%).
  
  
  CONCLUSIONS
  LPV/r monotherapy achieved satisfactory virologic efficacy in women treated solely for PMTCT, providing proof of concept for future nucleoside-sparing strategies.
authors.affiliation: Service de maladies infectieuses, AP-HP, Hôpital Pitié Salpêtrière, Paris, France. roland.tubiana@psl.aphp.fr
authors.forename: Roland
authors.initials: R
authors.lastname: Tubiana
authors.forename: Laurent
authors.initials: L
authors.lastname: Mandelbrot
authors.forename: Jérome
authors.initials: J
authors.lastname: Le Chenadec
authors.forename: Sandrine
authors.initials: S
authors.lastname: Delmas
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Deborah
authors.initials: D
authors.lastname: Hirt
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Treluyer
authors.forename: Dieudonné
authors.initials: D
authors.lastname: Ekoukou
authors.forename: Eda
authors.initials: E
authors.lastname: Bui
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Josiane
authors.initials: J
authors.lastname: Warszawski
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology*; D019438:Ritonavir / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D061466:Lopinavir; D019438:Ritonavir
keywords: HIV; PMTCT; lopinavir/ritonavir; monotherapy; zidovudine