Premature delivery in HIV-infected women starting protease inhibitor therapy during pregnancy: role of the ritonavir boost?

Clin Infect Dis. 2012 May;54(9):1348-60. doi: 10.1093/cid/cis198. Epub 2012 Mar 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • France / epidemiology
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / adverse effects*
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects*
  • Humans
  • Incidence
  • Infant, Newborn
  • Infant, Premature
  • Infectious Disease Transmission, Vertical / prevention & control
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy*
  • Pregnancy Complications, Infectious / virology
  • Premature Birth / chemically induced*
  • Premature Birth / epidemiology
  • Premature Birth / etiology
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Risk Factors
  • Ritonavir / adverse effects*
  • Ritonavir / therapeutic use
  • Zidovudine / adverse effects
  • Zidovudine / therapeutic use

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • Zidovudine
  • Ritonavir