Infants exposed to 3-drug antiretroviral therapy (ART) from conception have increased risk of adverse birth outcomes, but it is not known whether risk differs by ART regimen. We evaluated adverse birth outcomes by exposure to different ART regimens from conception.
We extracted obstetric records at 8 government hospitals in Botswana. Since 2012, Botswana guidelines have recommended TDF/FTC/EFV for adults with CD4<350 and all pregnant women; those stable on other regimens were not switched. Outcomes included stillbirth (SB), preterm delivery (PTD)(<37 weeks), small for gestational age (SGA)(<10th%), neonatal death (NND)(<28 days), and a combined endpoint of any adverse outcome. For singleton births, the adjusted risk ratio (aRR) of each outcome was determined using log binomial regression to evaluate the effect of HIV and ART exposures, adjusting for maternal age, parity and education.
From August 2014 to August 2016, 47180 infants were born at surveillance maternities, representing ~45% of all births in Botswana. Information was available for 47083 (99.8%): 34615 (74%) infants were HIV-unexposed, 11932 (25%) were HIV-exposed, and 479 (1%) unknown. Among HIV-exposed infants, 6178 (52%) were continuously ART-exposed from the time of conception, 4557 (38%) were ART-exposed starting in pregnancy, 1059 (9%) had no antiretroviral exposure, and 138 (1%) had unknown timing or exposure. Combined adverse birth outcomes were more common among all HIV-exposed infants than HIV-unexposed infants (34% vs. 24%, p<0.001). In adjusted models among singletons ART-exposed from conception, TDF/FTC/EFV was associated with the lowest risk for combined adverse birth outcomes (p<0.001). Compared with TDF/3TC/EFV, all other regimens were associated with higher risk of SGA; ZDV/3TC/NVP was associated with higher risk of SB, PTD and NND; and ZDV/3TC/LPV/r was associated with higher risk of PTD and NND (Table 1). Median CD4 (available for 25% exposed from conception) was 500 cells/mm3 (IQR 385, 683), and did not influence magnitude or direction of combined adverse outcomes when added to the model; nadir CD4 was not available. Time from ART start to conception, and neural tube defects by ART exposure, will be evaluated in future analyses.
Specific ART regimens used in pregnancy may impact adverse birth outcomes. Among infants exposed to ART from conception, TDF/FTC/EFV was associated with the fewest adverse birth outcomes.