Risk factors for pre-term birth in a Canadian cohort of HIV-positive women: Role of ritonavir boosting?

Fatima Kakkar, Isabelle Boucoiran, Valerie Lamarre, Thierry Ducruet, Devendra Amre, Hugo Soudeyns, Normand Lapointe, Marc Boucher

Research output: Contribution to journalArticle

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. Conclusion: 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.

Original languageEnglish (US)
Article number19933
JournalJournal of the International AIDS Society
Volume18
Issue number1
DOIs
StatePublished - Jun 5 2015
Externally publishedYes

Fingerprint

Term Birth
Ritonavir
Protease Inhibitors
HIV
Reverse Transcriptase Inhibitors
Mothers
Pregnancy
Maternal Exposure
Maternal Age
Live Birth
CD4 Lymphocyte Count
Hepatitis C
Parity
Coinfection
Nucleosides
Gestational Age
Obstetrics
Canada
Therapeutics
Logistic Models

Keywords

  • Antiretroviral drugs
  • HIV transmission
  • Mother-to-child prevention
  • Pre-term birth
  • Protease inhibitors

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Risk factors for pre-term birth in a Canadian cohort of HIV-positive women : Role of ritonavir boosting? / Kakkar, Fatima; Boucoiran, Isabelle; Lamarre, Valerie; Ducruet, Thierry; Amre, Devendra; Soudeyns, Hugo; Lapointe, Normand; Boucher, Marc.

In: Journal of the International AIDS Society, Vol. 18, No. 1, 19933, 05.06.2015.

Research output: Contribution to journalArticle

Kakkar, F, Boucoiran, I, Lamarre, V, Ducruet, T, Amre, D, Soudeyns, H, Lapointe, N & Boucher, M 2015, 'Risk factors for pre-term birth in a Canadian cohort of HIV-positive women: Role of ritonavir boosting?', Journal of the International AIDS Society, vol. 18, no. 1, 19933. https://doi.org/10.7448/IAS.18.1.19933
Kakkar, Fatima ; Boucoiran, Isabelle ; Lamarre, Valerie ; Ducruet, Thierry ; Amre, Devendra ; Soudeyns, Hugo ; Lapointe, Normand ; Boucher, Marc. / Risk factors for pre-term birth in a Canadian cohort of HIV-positive women : Role of ritonavir boosting?. In: Journal of the International AIDS Society. 2015 ; Vol. 18, No. 1.
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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. Conclusion: 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.",
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AU - Lamarre, Valerie

AU - Ducruet, Thierry

AU - Amre, Devendra

AU - Soudeyns, Hugo

AU - Lapointe, Normand

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N2 - 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. Conclusion: 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.

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KW - Antiretroviral drugs

KW - HIV transmission

KW - Mother-to-child prevention

KW - Pre-term birth

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