Response to “Antiretroviral Therapy With Efavirenz in HIV‐Infected Pregnant Women: Understanding the Possible Mechanisms for Drug–Drug Interaction”
We also agree with Dr. Srinivas that induction of CYP3A4 by efavirenz may also influence PQ clearance, thereby leading to a reduced PQ half‐life.5 This can most easily be explained by an induction of hepatic metabolism that has clearly been demonstrated for efavirenz.3
As stated by Dr. Srinivas and as we concluded in our article, we agree that these drug interactions may have critically important clinical consequences. We have recently performed population pharmacokinetic/pharmacodynamic (PK/PD) modeling from these trials, and have estimated that maintaining a protective PQ concentration of >10.3 ng/mL was associated with 95% protection from maternal malaria and parasitemia among HIV‐uninfected women given DHA‐PQ (Savic R, Jagannathan P, Kajubi R, Huang L, Zhang N, Were M, et al., unpublished data). In women receiving efavirenz‐based ART and standard monthly DHA‐PQ as IPTp, less than 1% achieved these protective PQ levels during pregnancy (Wallender E, Vucicevic K, Jagannathan P, Huang L, Natureeba P, Kakuru A, et al., unpublished data). Optimizing the dosing of DHA‐PQ for chemoprevention in the setting of a drug–drug interactions will be an essential advancement in malaria control.