Pharmacokinetics and drug-drug interactions of isoniazid and efavirenz in pregnant women living with HIV in high TB incidence settings: importance of genotyping

Citation: Gausi K, Wiesner L, Norman J, Wallis CL, Onyango-Makumbi C, Chipato T, Haas DW, Browning R, Chakhtoura N, Montepiedra G, Aaron L, McCarthy K, Bradford S, Vhembo T, Stranix-Chibanda L, Masheto GR, Violari A, Mmbaga BT, Aurpibul L, Bhosale R, Nevrekhar N, Rouzier V, Kabugho E, Mutambanengwe M, Chanaiwa V, Nyati M, Mhembere T, Tongprasert F, Hesseling A, Shin K, Zimmer B, Costello D, Jean-Philippe P, Sterling TR, Theron G, Weinberg A, Gupta A, Denti P; IMPAACT P1078 (TB APPRISE) Study Group Team. Pharmacokinetics and drug-drug interactions of isoniazid and efavirenz in pregnant women living with HIV in high TB incidence settings: importance of genotyping. Clin Pharmacol Ther. 2020 Sep 9. doi: 10.1002/cpt.2044. Epub ahead of print. PMID: 32909316.

Access full article:

https://pubmed.ncbi.nlm.nih.gov/32909316/

World Health Organization guidelines recommend that individuals living with HIV receive ≥6 months of isoniazid preventive therapy, including pregnant women. Yet, plasma isoniazid exposure during pregnancy, in the antiretroviral therapy era, has not been well described. We investigated pregnancy-induced and pharmacogenetic-associated pharmacokinetic changes and drug-drug-interactions between isoniazid and efavirenz in pregnant women. 847 women received isoniazid for 28 weeks, either during pregnancy or at 12 weeks postpartum, and 786 women received efavirenz. After adjusting for NAT2 and CYP2B6 genotype and weight, pregnancy increased isoniazid and efavirenz clearance by 26% and 15%, respectively. Isoniazid decreased efavirenz clearance by 7% in CYP2B6 normal metabolizers and 13% in slow and intermediate metabolizers. Overall, both isoniazid and efavirenz exposures were reduced during pregnancy, but the main determinants of drug concentration were NAT2 and CYP2B6 genotypes, which resulted in a 5-fold difference for both drugs between rapid and slow metabolizers.

Categories

CRS
Topics

Clinical Trials

Identification of Biomarkers That Can Predict Progression...

Purpose: The C-TRIUMPH study has identified 20 household contacts (HHC), who have progressed to active TB from its HHCs cohort...

Read More

P1078: A Phase IV Randomized Double-Blind Placebo-Controlled...

P1078 is a Phase IV, randomized, double-blind, placebo-controlled study of HIV-infected pregnant women and the infants born to...

Read More

A5342: Evaluating the Safety, Tolerability, and Effect of a...

The purpose of this study is to evaluate the safety, tolerability, and effect of an experimental human monoclonal antibody...

Read More

A5207, Maintaining Options for Mothers Study (MOMS): A Phase...

A major disadvantage of giving SD NVP is the potential for maternal development of NVP resistance and additional resistance to...

Read More

A5300/P2003: PHOENIx Feasibility Study

Study of MDR TB Cases and Their Household Contacts: Operational Feasibility to Inform PHOENIx Trial Design

Read More