title: Premature delivery in HIV-infected women starting protease inhibitor therapy during pregnancy: role of the ritonavir boost?
abstract: BACKGROUND
  The association between combination antiretroviral (cARV) therapy use by human immunodeficiency virus (HIV)-infected women during pregnancy and risk of prematurity is still controversial. We explored this question, focusing on the initiation of ritonavir-boosted protease inhibitors (PIs) during pregnancy, which is now standard care.
  
  
  METHODS
  Trends in prematurity (<37 gestational weeks) were studied among all singleton pregnancies in the Agence Nationale de Recherche sur le SIDA (ANRS) French Perinatal Cohort from 1990 through 2009 (n = 13 271). In-depth analysis was conducted in a more detailed substudy of the cohort, among women starting PI-based ARV therapy during pregnancy (n = 1253). Multivariable analysis adjusted for immunovirological status and known risk factors for prematurity.
  
  
  RESULTS
  Prematurity increased from 9.2% during 1990-1993 (no therapy) and 9.6% during 1994-1996 (mostly zidovudine monotherapy) to 12.4% during 1997-1999 (dual-nucleoside analog therapy) and 14.3% during 2005-2009 (routine cARV therapy; P < .01). Prematurity was associated with cARV therapy, compared with zidovudine monotherapy, with an adjusted odds ratio of 1.69 (95% confidence interval [CI], 1.38-2.07; P < .01) when accounting for maternal age, intravenous drug use, geographic origin, and CD4 cell count. During 2005-2009, the prematurity rate was higher with boosted than with nonboosted PI therapy started during pregnancy (14.4% vs 9.1% [P = .05]; adjusted hazard ratio, 2.03 [95% CI, 1.06-3.89; P = .03] in multivariate analysis). The difference concerned mainly induced preterm delivery for maternal or fetal indications (5.6% vs 1.6%; P = .02),
  
  
  CONCLUSIONS
  The prematurity rate among HIV-infected pregnant women was twice that in the general population in France; this was not entirely explained by sociodemographic characteristics. Prematurity was independently associated with cARV therapy and, particularly, with the initiation of ritonavir-boosted PI therapy during pregnancy.
authors.affiliation: CESP INSERM U1018, Le Kremlin-Bicêtre, Colombes, France. jeannesibiude@yahoo.fr
authors.forename: Jeanne
authors.initials: J
authors.lastname: Sibiude
authors.forename: Josiane
authors.initials: J
authors.lastname: Warszawski
authors.forename: Roland
authors.initials: R
authors.lastname: Tubiana
authors.forename: Catherine
authors.initials: C
authors.lastname: Dollfus
authors.forename: Albert
authors.initials: A
authors.lastname: Faye
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Teglas
authors.forename: Dieudonné
authors.initials: D
authors.lastname: Ekoukou
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Laurent
authors.initials: L
authors.lastname: Mandelbrot
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005602:France / Q000453:epidemiology; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007234:Infant, Premature; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D047928:Premature Birth / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D019438:Ritonavir / Q000009:adverse effects* / Q000627:therapeutic use; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019438:Ritonavir