Prevention of TB using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants
Year: 2017
Type: article
Study design: Observational Study
Abstract: Background: Newborns of HIV-infected mothers are given daily doses of nevirapine to prevent HIV-1 acquisition. Infants born to mothers with TB should also receive TB preventive therapy. TB preventive regimens include isoniazid for 6 months or rifampicin plus isoniazid for 3 months (RH preventive therapy). The effect of concomitant RH preventive therapy on nevirapine concentrations in infants is unknown. Patients and methods: Tshepiso was a prospective case-control cohort study of pregnant HIV-infected women with and without TB whose newborn infants received standard doses of nevirapine for HIV prophylaxis. Infants born to mothers with TB also received RH preventive therapy. Infant plasma nevirapine concentrations were measured at 1 and 6 weeks. The effects of RH preventive therapy on nevirapine disposition were investigated in a population pharmacokinetic model. Results: Of 164 infants undergoing pharmacokinetic sampling, 46 received RH preventive therapy. After adjusting for weight using allometric scaling, the model estimated a 33% reduction in nevirapine trough concentrations with RH preventive therapy compared with TB-unexposed infants not receiving concomitant rifampicin and a 30% decline in trough concentrations in a typical infant between day 7 and 35 post-partum. Conclusions: Rifampicin-based TB preventative treatment reduces nevirapine concentrations significantly in HIV-exposed infants. Although the nevirapine exposures required to prevent HIV acquisition in breastfeeding infants are undefined, given the potential risks associated with underdosing nevirapine in this setting, it is prudent to avoid rifampicin-based preventive therapy in HIV-exposed children receiving prophylactic nevirapine.
DOI: 10.1093/jac/dkx112
Authors: Helen McIlleron, Paolo Denti, Silvia Cohn, Fildah Mashabela, Jennifer D. Hoffmann, Saba Shembe, Regina Msandiwa, Lubbe Wiesner, Sithembiso Velaphi, Sanjay G. Lala, Richard E. Chaisson, Neil Martinson, Kelly E. Dooley, on behalf of the Tshepiso Study Team
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Johns Hopkins University, National Research Foundation, University of Cape Town, National Institutes of Health, Center for AIDS Research, University of Washington, Center for AIDS Research, Johns Hopkins University, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1571747198, G1597187361, G1819583291, G2483435703, G2560876791, G285461174, PK/PD Issues in the Use of New Therapies for the Treatment of Tuberculosis, G308165101, G3261282631, G3463285819, G3810609436, G4273213264, G5632036211, Impact of TB on Outcome of HIV in Pregnant Women, International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group, G622809771, G653582874, G7178514535, G7742187551, G8199594878, G8217102994, G8653183194, G9000014638, G9000039438, G9000292181, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, The Johns Hopkins Center for AIDS Research (JHU CFAR), AIDS Clinical Trial Group Laboratory Center, Statistical and Data Management Center (SDMC), Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG), IMPAACT Leadership Group, G97774765
OpenAlex ID: W2605981448