NRTI backbones and pregnancy outcomes: results from a European cohort collaboration.

OBJECTIVES: to investigate whether specific nucleoside reverse transcriptase inhibitor (NRTI) backbones are associated with risk of adverse pregnancy outcomes among pregnant women starting antiretroviral therapy (ART) DESIGN:: Seven observational studies across eight European countries of pregnancies in HIV-positive women METHODS:: Individual-level data were pooled on singleton pregnancies conceived off-ART in which a single combination ART regimen was initiated ≥2 weeks before delivery, and ending in a live birth in 2008-2014. Preterm delivery (PTD) was defined as <37 gestational weeks and small-for-gestational-age (SGA) as <10 percentile according to INTERGROWTH standards. Poisson regression models were fitted to investigate associations between NRTI backbones and PTD/SGA.

RESULTS: Of 7193 pregnancies, 45% (3207) were in UK/Ireland, 44% (3134) in Ukraine. 10% (722/7193) of deliveries were preterm and 11.1% (785/7089) of newborns SGA. The most common NRTI backbones were ZDV-3TC (71%), TDF-XTC (16%) and ABC-3TC (10%) with TDF-containing backbone use increasing over time. Overall, 77% of regimens contained LPV/r. There was no association between NRTI backbone and PTD in main adjusted analyses (adjusted prevalence ratios (aPR) 0.97 [95%CI 0.73-1.28] for ABC-3TC and aPR 1.06 [0.83-1.35] for TDF-XTC, both vs ZDV-3TC) or in 4720 pregnancies on LPV/r (aPR 1.03 [0.74-1.43] for ABC-3TC and aPR 1.16 [0.85-1.57] for TDF-XTC, both vs ZDV-3TC). Infants exposed to ABC-3TC or TDF-XTC in-utero were less likely to be SGA than those exposed to ZDV-3TC (aPR 0.72 [0.53-0.97] and aPR 0.70 [0.53-0.93] respectively).

CONCLUSIONS: Results support the safety of TDF-XTC backbones initiated in pregnancy with respect to gestation length and birthweight.