A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women

Background: Reducing the dose of efavirenz can improve safety, reduce costs, and increase access for patients with HIV infection. According to the World Health Organization, a similar dosing strategy for all patient populations is desirable for universal roll-out; however, it remains unknown whether the 400 mg daily dose is adequate during pregnancy. Methods: We developed a mechanistic population pharmacokinetic model using pooled data from women included in seven studies (1968 samples, 774 collected during pregnancy). Total and free efavirenz exposure (AUC₂₄ and C₁₂) were predicted for 400 (reduced) and 600 mg (standard) doses in both pregnant and non-pregnant women. Results: Using a 400 mg dose, the median efavirenz total AUC₂₄ and C₁₂ during the third trimester of pregnancy were 91 and 87% of values among non-pregnant women, respectively. Furthermore, the median free efavirenz C₁₂ and AUC₂₄ were predicted to increase during pregnancy by 11 and 15%, respectively. Conclusions: It was predicted that reduced-dose efavirenz provides adequate exposure during pregnancy. These findings warrant prospective confirmation.