TY - JOUR
T1 - Pharmacokinetics of Efavirenz 600 mg Once Daily During Pregnancy and Post Partum in Ghanaian Women Living With HIV
AU - Lartey, Margaret
AU - Kenu, Ernest
AU - Lassey, Anyetei
AU - Ntumy, Michael
AU - Ganu, Vincent
AU - Sam, Miriam
AU - Boamah, Isaac
AU - Gilani, Fizza S.
AU - Yang, Hongmei
AU - Burch, Gena M.
AU - Norman, Jennifer
AU - Peloquin, Charles A.
AU - Kwara, Awewura
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/9
Y1 - 2020/9
N2 - Purpose: The updated World Health Organization guidelines recommend efavirenz (EFV) 400 mg as the preferred alternate first-line antiretroviral therapy to dolutegravir, with EFV 600 mg recommended only in special situations. We examined the pharmacokinetic (PK) properties of EFV 600 mg/d during pregnancy and post partum to inform EFV dosing decisions in pregnant women. Methods: Ghanaian pregnant women with HIV infection initiating tenofovir disoproxil fumarate 300 mg/lamivudine 300 mg/EFV 600 mg fixed-dose combination tablet once daily were enrolled. Efavirenz concentrations were measured at 4 weeks of antiretroviral therapy initiation during pregnancy and 6 weeks post partum using validated LC-MS/MS assays. Efavirenz PK parameters were calculated using noncompartmental analysis, and within-group parameters between the 2 periods were compared. Findings: Of 25 enrolled women, 19 completed PK sampling during pregnancy and post partum. The Cmax, Cmin, AUC0–24h, and CL/F for EFV during pregnancy were similar to values at 6 weeks post partum. The pregnancy/postpartum geometric mean ratios for EFV Cmax, Cmin, AUC0–24, and CL/F were 1.10 (95% CI, 0.93–1.31), 0.88 (95% CI, 0.67–1.17), 0.84 (95% CI, 0.71–0.98), and 1.20 (95% CI, 1.02–1.40), respectively. Viral load suppression (HIV RNA <200 copies/mL) was achieved in 16 of 17 participants (94%) by the time of delivery. There was 1 maternal-to-child transmission. Implications: We found that the PK parameters of EFV 600 mg once daily during pregnancy were similar to those in the postpartum period. Our findings suggest that EFV dose adjustment during pregnancy is not necessary in our study population.
AB - Purpose: The updated World Health Organization guidelines recommend efavirenz (EFV) 400 mg as the preferred alternate first-line antiretroviral therapy to dolutegravir, with EFV 600 mg recommended only in special situations. We examined the pharmacokinetic (PK) properties of EFV 600 mg/d during pregnancy and post partum to inform EFV dosing decisions in pregnant women. Methods: Ghanaian pregnant women with HIV infection initiating tenofovir disoproxil fumarate 300 mg/lamivudine 300 mg/EFV 600 mg fixed-dose combination tablet once daily were enrolled. Efavirenz concentrations were measured at 4 weeks of antiretroviral therapy initiation during pregnancy and 6 weeks post partum using validated LC-MS/MS assays. Efavirenz PK parameters were calculated using noncompartmental analysis, and within-group parameters between the 2 periods were compared. Findings: Of 25 enrolled women, 19 completed PK sampling during pregnancy and post partum. The Cmax, Cmin, AUC0–24h, and CL/F for EFV during pregnancy were similar to values at 6 weeks post partum. The pregnancy/postpartum geometric mean ratios for EFV Cmax, Cmin, AUC0–24, and CL/F were 1.10 (95% CI, 0.93–1.31), 0.88 (95% CI, 0.67–1.17), 0.84 (95% CI, 0.71–0.98), and 1.20 (95% CI, 1.02–1.40), respectively. Viral load suppression (HIV RNA <200 copies/mL) was achieved in 16 of 17 participants (94%) by the time of delivery. There was 1 maternal-to-child transmission. Implications: We found that the PK parameters of EFV 600 mg once daily during pregnancy were similar to those in the postpartum period. Our findings suggest that EFV dose adjustment during pregnancy is not necessary in our study population.
KW - maternal-to-child transmission
KW - pharmacokinetics
KW - post partum
KW - pregnancy
KW - standard-dose efavirenz
UR - http://www.scopus.com/inward/record.url?scp=85089460268&partnerID=8YFLogxK
U2 - 10.1016/j.clinthera.2020.07.008
DO - 10.1016/j.clinthera.2020.07.008
M3 - Article
C2 - 32811669
AN - SCOPUS:85089460268
SN - 0149-2918
VL - 42
SP - 1818
EP - 1825
JO - Clinical Therapeutics
JF - Clinical Therapeutics
IS - 9
ER -