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

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.