Background: A premarket primate study associated 1st trimester efavirenz (EFV) exposure to anomalies of the CNS and NT. In humans, a meta-analysis failed to identify any increased risk despite a reported increased risk of neurological defects associated with EFV exposure. We describe CNS/NT defects in the APR, a voluntary, international, prospective exposure-registration cohort study with independent Advisory Committee oversight.
Methods: Prospective enrollments with birth outcome through July 2014 are included. Defects are coded according to MACDP criteria. Relative risk (RR) of 1st vs 2nd/3rd trimester antiretroviral (ARV) exposure and 95% confidence intervals (CI) are calculated using the normal asymptotic method. P-values use Fishers Exact test. First trimester EFV exposed infants were compared internally to three groups; 1) pregnancies exposed to EFV beginning in the 2nd/3rd trimester, 2) pregnancies never exposed to EFV but received other ARVs at any time, 3) pregnancies exposed to other non-EFV ARVs during the 1st trimester.
Results: A total of 17,043 pregnancies resulted in 17,335 outcomes (16,150 livebirths). There were 460 defect cases including 40 CNS (7 NT) of which 15 CNS (2 NT) had ARV exposure during the 1st trimester (see table). RR of CNS defects with earliest known ARV exposure in 1st vs 2nd/3rd trimester was 0.71 (95% CI: 0.37, 1.35; p-value: 0.34). RR of NT defects with earliest known ARV exposure in 1st vs 2nd/3rd trimester was 0.47 (95% CI: 0.09, 2.45, p-value: 0.46). There were 2 CNS defect cases (1 NT) with EFV exposure in the 1st trimester. There were no statistically significant differences between the 1st trimester EFV exposed cohort and the three internal comparison groups (p-value 1.0, 1.0, and 0.68, respectively).
Conclusion: This analysis of 17,335 prospective birth outcomes found no evidence of increased risk of CNS/NT defects when comparing earliest ARV exposure in the 1st vs 2nd/3rd trimester. APR data do not support other reports of increased risk of CNS/NT defects in outcomes with 1st trimester EFV exposure. The APR concludes, The Antiretroviral Pregnancy Registry finds no apparent increases in frequency of specific defects with first trimester exposures and no pattern to suggest a common cause; however, potential limitations of registries should be recognized.
L. Mofenson, None
A. Pikis, None
A. Scheuerle, None
W. Short, None
D. Seekins, BMS: Employee , Salary
V. Vannappagari, ViiV Healthcare: Employee , GSK stock as part of compensation and Salary
H. Tilson, None
H. Watts, None
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