Repeat Pregnancies Among US Women Living With HIV in the SMARTT Study: Temporal Changes in HIV Disease Status and Predictors of Preterm Birth

Abstract

BACKGROUND-Birth rates among women living with HIV (WLHIV) have increased recently, with many experiencing multiple pregnancies. Yet, viral suppression is often not sustained between pregnancies. Additionally, protease inhibitors (PIs) have been associated with preterm birth, but associations between integrase strand transfer inhibitors (INSTIs) and preterm birth are less well characterized.METHODS-We studied WLHIV with ≥2 liveborn infants enrolled into the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring for ART Toxicities (SMARTT) study between 2007-2018, comparing CD4 counts and viral loads (VLs) between two consecutive SMARTT pregnancies. We evaluated associations of covariates with CD4 and viral suppression, and the association of PI/INSTI use during pregnancy with odds of preterm birth.RESULTS-There were 736 women who had ≥2 liveborn children enrolled in SMARTT (1695 pregnancies). Median CD4 counts remained stable over repeat pregnancies. While > 80% of women achieved VL suppression during pregnancy, more than half had detectable VL early in their subsequent pregnancy. In adjusted models including all singleton pregnancies, an increased odds of preterm birth was observed for women with 1 st trimester PI initiation (adjusted odds ratio [OR] 1.97; 95% CI 1.27, 3.07) compared to those not receiving PIs during pregnancy, and for 1 st trimester INSTI initiation (adjusted OR 2.39; 95% CI 1.04, 5.46) compared to those never using INSTIs during pregnancy. CONCLUSIONS-MostWLHIV achieved VL suppression by late pregnancy but many were viremic early in subsequent pregnancies. First trimester initiation of PIs or INSTIs was associated with higher risk of preterm birth.

Congenital Malformations and Preeclampsia Associated with Integrase Inhibitor Use in Pregnancy

“…Other studies have identified an association between INSTI exposure during pregnancy and preterm birth. [18] Of note, our comparison group included women who received PIs, which are associated with increased rates of preterm birth [35,36]; this may have limited our ability to detect an association between INSTI exposure and preterm birth, should one exist. We noted that women on INSTI had fewer grade ≥3 chemistry and hematology laboratory abnormalities compared to women on non-INSTI regimens, although this could not be compared in a formal statistical analysis.…”

“…Other studies have identified an association between INSTI exposure during pregnancy and preterm birth. [18] Of note, our comparison group included women who received PIs, which are associated with increased rates of preterm birth [35, 36]; this may have limited our ability to detect an association between INSTI exposure and preterm birth, should one exist.…”

“…Pregnancies were categorized as having DTG or any INSTI exposure if a mother received these drugs at any time between conception and delivery. ART was categorized by timing of receipt, in the first (gestational age ≤13 weeks), second (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), or third (28-delivery) trimesters. Laboratory abnormalities were graded according to the 2017 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events with pregnancy-specific modifications.…”

“…[4,5,[15][16][17] In contrast, the SMARTT study identified a 2-fold higher rate of preterm birth among infants with first-trimester INSTI exposure compared to no INSTI exposure. [18] Few studies have compared maternal outcomes such as preeclampsia, gestational diabetes, and laboratory abnormalities between pregnancies exposed to INSTIs versus other ART. [19,20] The objective of this study was to compare rates of congenital anomalies and adverse maternal and pregnancy outcomes between INSTI-exposed mother-infant dyads and those exposed to PI-or non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens.…”

“…[4, 5, 15-17] In contrast, the SMARTT study identified a 2-fold higher rate of preterm birth among infants with first-trimester INSTI exposure compared to no INSTI exposure. [18] Few studies have compared maternal outcomes such as preeclampsia, gestational diabetes, and laboratory abnormalities between pregnancies exposed to INSTIs versus other ART. [19, 20]…”