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

Abstract

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 C_max, C_min, AUC_0-24h, and CL/F for EFV during pregnancy were similar to values at 6 weeks post partum. The pregnancy/postpartum geometric mean ratios for EFV C_max, C_min, AUC_0-24, 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.

Keywords: maternal-to-child transmission; pharmacokinetics; post partum; pregnancy; standard-dose efavirenz.

Fig. 1.

Median efavirenz plasma concentrations during pregnancy (median 23 weeks gestation) and median 6 weeks postpartum plotted by sampling time after dosing among Ghanaian women.

Fig. 2.

Change in efavirenz CL/F (A), AUC_0-24h (B), C_min (C) and C_12h during pregnancy and postpartum in 19 Ghanaian women with paired samples. Signed-rank test P value for median change in pharmacokinetic parameters between the two periods (dotted line) is reported.