title: Risk factors for pre-term birth in a Canadian cohort of HIV-positive women: role of ritonavir boosting?
abstract: BACKGROUND
  The risk of pre-term birth (PTB) associated with the use of protease inhibitors (PIs) during pregnancy remains a subject of debate. Recent data suggest that ritonavir boosting of PIs may play a specific role in the initiation of PTB, through an effect on the maternal-fetal adrenal axis. The primary objective of this study is to compare the risk of PTB among women treated with boosted PI versus non-boosted PIs during pregnancy.
  
  
  METHODS
  Between 1988 and 2011, 705 HIV-positive women were enrolled into the Centre Maternel et Infantile sur le SIDA mother-infant cohort at Centre Hospitalier Universitaire Sainte-Justine in Montreal, Canada. Inclusion criteria for the study were: 1) attendance at a minimum of two antenatal obstetric visits and 2) singleton live birth, at 24 weeks gestational or older. The association between PTB (defined as delivery at <37 weeks gestational age), antiretroviral drug exposure and maternal risk factors was assessed retrospectively using logistic regression.
  
  
  RESULTS
  A total of 525 mother-infant pairs were included in the analysis. Among them, PI-based combination anti-retroviral therapy was used in 37.4%, boosted PI based in 24.4%, non-nucleoside reverse transcriptase inhibitor (NNRTI) or nucleoside reverse transcriptase inhibitor based in 28.1%, and no treatment was given in 10.0% of cases. Overall, 13.5% of women experienced PTB. Among women treated with antiretroviral therapy, the risk of PTB was significantly higher among women who received boosted versus non-boosted PI (OR 2.01, 95% CI 1.02-3.97). This remained significant after adjusting for maternal age, delivery CD4 count, hepatitis C co-infection, history of previous PTB, and parity (aOR 2.17, 95% CI 1.05-4.51). There was no increased risk of PTB with the use of unboosted PIs as compared to NNRTI- or NRTI-based regimens.
  
  
  CONCLUSIONS
  While previous studies on the association between PTB and PI use have generally considered all PIs the same, our results would indicate a possible role of ritonavir boosting as a risk factor for PTB. Further work is needed to understand the pathophysiologic mechanisms involved, and to identify the safest ARV regimens to be used in pregnancy.
authors.affiliation: Division of Infectious Diseases, CHU Sainte-Justine, Montréal, Canada;|Department of Pediatrics, Faculty of Medicine, Université de Montréal, Montreal, Canada.|Centre maternel et infantile sur le SIDA, CHU Sainte-Justine, Montreal, Canada; fatima.kakkar@umontreal.ca.
authors.forename: Fatima
authors.initials: F
authors.lastname: Kakkar
authors.affiliation: Centre maternel et infantile sur le SIDA, CHU Sainte-Justine, Montreal, Canada.|Department of Obstetrics and Gynecology, Université de Montréal, CHU Sainte-Justine, Montreal, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boucoiran
authors.affiliation: Division of Infectious Diseases, CHU Sainte-Justine, Montréal, Canada;|Department of Pediatrics, Faculty of Medicine, Université de Montréal, Montreal, Canada.|Centre maternel et infantile sur le SIDA, CHU Sainte-Justine, Montreal, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Lamarre
authors.affiliation: Unité de recherche clinique appliquée, CHU Sainte-Justine, Montréal, Canada.
authors.forename: Thierry
authors.initials: T
authors.lastname: Ducruet
authors.affiliation: Centre de recherche du CHU Sainte-Justine, Montréal, Canada.
authors.forename: Devendra
authors.initials: D
authors.lastname: Amre
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Université de Montréal, Montreal, Canada.|Centre de recherche du CHU Sainte-Justine, Montréal, Canada.|Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, Université de Montréal, Montréal, Canada.
authors.forename: Hugo
authors.initials: H
authors.lastname: Soudeyns
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Université de Montréal, Montreal, Canada.|Centre maternel et infantile sur le SIDA, CHU Sainte-Justine, Montreal, Canada.
authors.forename: Normand
authors.initials: N
authors.lastname: Lapointe
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Université de Montréal, Montreal, Canada.|Centre maternel et infantile sur le SIDA, CHU Sainte-Justine, Montreal, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Boucher
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D005260:Female; D006679:HIV Seropositivity / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007223:Infant; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology*; D012189:Retrospective Studies; D012307:Risk Factors; D019438:Ritonavir / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D019438:Ritonavir
keywords: HIV transmission; antiretroviral drugs; mother-to-child prevention; pre-term birth; protease inhibitors