MOAB0303 - Oral Abstract
Efavirenz (EFV) concentrations in pregnant women taking EFV-based antiretroviral therapy (ART) with and without rifampin-containing tuberculosis (TB) treatment: the TSHEPISO Study Team
Presented by Kelly E Dooley (United States).
H. McIlleron1, N. Martinson2,3, P. Denti1, F. Mashabela2, J. Hunt3, S. Shembe2, J. Hull4, D.W. Haas5, R. Msandiwa2, S. Cohn3, R. Chaisson3, K.E. Dooley3, TSHEPISO Study Team
1University of Cape Town, Cape Town, South Africa, 2Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Soweto, South Africa, 3Johns Hopkins University School of Medicine, Baltimore, United States, 4Chris Hani Baragwanath Hospital and University of the Witwatersrand, Department of Obstetrics, Soweto, South Africa, 5Vanderbilt University, Nashville, United States
Background: HIV and TB are threats to pregnant women and infants. Treatment with rifampin can reduce ART concentrations and increase risk of treatment failure and vertical transmission. We describe the pharmacokinetics (PK) and pharmacodynamics of EFV among pregnant HIV-infected women.
Methods: Prospective cohort of HIV-infected pregnant women with and without TB in Soweto. Women taking ART with EFV 600mg had PK sampling at 37 weeks' gestation or at delivery and then six weeks post-partum. EFV concentrations were measured in cord blood at delivery and in infants at 7 days. Post-hoc Bayesian estimates of PK parameters from nonlinear mixed-effects modeling with allometric scaling are reported.
Results: Among 41 HIV-infected pregnant women taking EFV ART, 19 received rifampin (TB/HIV) and 22 ART alone. Median age and weight were 29 years and 70 kg. For 35 women with pre-/peripartum EFV PK, median (IQR) estimated EFV trough (Cmin) was 1.31 (0.84, 1.86)mg/L, apparent oral clearance (CL/F) 13.62 (10.67, 18.44)L/h, and volume of distribution (Vd/F) 516 (440, 591)L. 31% had Cmin< 1 mg/L. Predicted median Cmin by CYP2B6 516/983 metabolizer genotype was: 1.04 (extensive), 1.34 (intermediate), and 4.36 mg/L (slow). TB treatment did not significantly affect EFV Cmin (1.28 v 1.42mg/L). 5/26 women tested at delivery had viral load >20 copies/mL (one had TB/HIV). Median cord blood EFV concentration was 1.09 (0.46, 2.38)mg/L. EFV concentrations were BLQ in 6/24 cord blood and 25/30 infant 7-day samples; both correlated with maternal concentrations. 0/35 infants were HIV-infected at 6 weeks. In mothers 6 weeks postpartum, median EFV Cmin was 1.75mg/L, CL/F 10.79L/h, and Vd/F 433L; 30% had Cmin< 1mg/L.
Conclusions: TB treatment did not significantly reduce EFV Cmin, but pregnancy may lower EFV concentrations. Although ~30% of pregnant women had EFV Cmin< 1mg/L at standard doses, EFV-containing ART suppressed viral load in most and there were no vertical transmissions.
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