Pharmacokinetics of Efavirenz 600 mg Once Daily During Pregnancy and Post Partum in Ghanaian Women Living With HIV

• Published in: Clinical therapeutics 2020-09, Vol.42 (9), p.1818-1825
• Main Authors: Lartey, Margaret, Kenu, Ernest, Lassey, Anyetei, Ntumy, Michael, Ganu, Vincent, Sam, Miriam, Boamah, Isaac, Gilani, Fizza S., Yang, Hongmei, Burch, Gena M., Norman, Jennifer, Peloquin, Charles A., Kwara, Awewura
• Format: Article
• Language: English
• Subjects: Adult; Alkynes - administration & dosage; Alkynes - pharmacokinetics; Anti-HIV Agents - pharmacokinetics; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Benzoxazines - administration & dosage; Benzoxazines - pharmacokinetics; Blood; Chromatography, Liquid; Cyclopropanes - administration & dosage; Cyclopropanes - pharmacokinetics; Dosage; Drug dosages; Efavirenz; Enzymes; Female; Gestational age; Ghana; HIV; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical - statistics & numerical data; Lamivudine; Lamivudine - therapeutic use; maternal-to-child transmission; Pharmacokinetics; Pharmacology; Plasma; Population studies; post partum; Postpartum; Postpartum Period; Pregnancy; Prevention; Ribonucleic acid; RNA; Software; standard-dose efavirenz; Tandem Mass Spectrometry; Tenofovir; Tenofovir - therapeutic use; Viral Load; Womens health; Young Adult
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2020.07.008

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. 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. 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