Type and timing of antiretroviral therapy during pregnancy: Impact on risk of preterm delivery and small‐for‐gestational age births in Canada, a retrospective cohort study

Abstract

Objective To evaluate the impact of type and timing of antiretroviral therapy (ART) on the risk of preterm delivery (PTD) and small‐for‐gestational age (SGA) birth among pregnant women and people living with HIV in Canada. Methods Data for this retrospective cohort study were analyzed from the Canadian Perinatal HIV Surveillance Program from 1990 to 2020. The association between ART and risk of PTD (<37 weeks) and SGA birth (<10th percentile) was explored using mixed effects logistic regression and time‐dependent Cox proportional hazards models. Results Overall, there were 14.9% (654 of 4379) PTD and 18.5% (732 of 3947) SGA cases. A higher risk of PTD was observed with nonnucleoside reverse transcriptase inhibitor–(adjusted hazard ratio [aHR], 1.73; P = 0.019) and boosted protease inhibitor– (aHR, 186; P = 0.007) based regimens compared with integrase strand transfer inhibitor (INSTI)–based regimens. ART initiation prior to conception was associated with a lower risk of SGA birth compared with ART initiation after conception at 1 to 14 weeks (adjusted odds ratio [aOR], 0.69; P = 0.024) and > 14 weeks (aOR, 0.70; P = 0.005). Conclusion INSTI‐based ART regimens were associated with lower risk of PTD compared with other regimens, and ART initiation before conception was associated with a lower risk of SGA birth. These findings, with overall safety data, should be considered when providing pregnancy counseling to people living with HIV.

Circulating levels of inflammatory mediators in pregnant people living with HIV according to antiretroviral therapy regimen

“…A meta-analysis as well as cohort studies have found that exposure to PI-based regimens compared to other regimens is significantly associated with preterm delivery ( Mesfin et al, 2016 ; Schneidman et al, 2023 ). Additionally, induction of pro-inflammatory cytokine release has been linked to preterm delivery, although the timing of this release seems to be an important factor ( Curry et al, 2007 ).…”

“…Despite a decreasing rate of vertical transmission of Human Immunodeficiency Virus (HIV) due to the use of Antiretroviral therapy (ART) during pregnancy, recent studies have shown that adverse pregnancy outcomes are still prevalent among people living with HIV (PLWH), especially preterm delivery ( Tukei et al, 2021 ). In particular, in some reports, these outcomes have been associated with protease inhibitor (PI)-based regimens, although this outcome is largely variable in the literature ( Favarato et al, 2018 ; Albert et al, 2020 ; Schneidman et al, 2022 ).…”