Prevention of TB using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants

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, Matebogu Letutu, Susan Raedani, Ziyaad Waja, Chris Hoffmann, Jenny Hull, Yudesh Baliram, on behalf of the Tshepiso Study Team

Research output: Research - peer-reviewArticle

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 6months or rifampicin plus isoniazid for 3months (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.

LanguageEnglish (US)
Article numberdkx112
Pages2028-2034
Number of pages7
JournalJournal of Antimicrobial Chemotherapy
Volume72
Issue number7
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

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Nevirapine
Isoniazid
Rifampin
HIV
Therapeutics
Mothers
Pharmacokinetics
Newborn Infant
Breast Feeding
HIV-1
Case-Control Studies
Cohort Studies
Weights and Measures
Population

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

McIlleron, H., Denti, P., Cohn, S., Mashabela, F., Hoffmann, J. D., Shembe, S., ... on behalf of the Tshepiso Study Team (2017). Prevention of TB using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants. Journal of Antimicrobial Chemotherapy, 72(7), 2028-2034. [dkx112]. DOI: 10.1093/jac/dkx112

Prevention of TB using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants. / McIlleron, Helen; Denti, Paolo; Cohn, Silvia; Mashabela, Fildah; Hoffmann, Jennifer D.; Shembe, Saba; Msandiwa, Regina; Wiesner, Lubbe; Velaphi, Sithembiso; Lala, Sanjay G.; Chaisson, Richard E.; Martinson, Neil; Dooley, Kelly E.; Letutu, Matebogu; Raedani, Susan; Waja, Ziyaad; Hoffmann, Chris; Hull, Jenny; Baliram, Yudesh; on behalf of the Tshepiso Study Team.

In: Journal of Antimicrobial Chemotherapy, Vol. 72, No. 7, dkx112, 01.07.2017, p. 2028-2034.

Research output: Research - peer-reviewArticle

McIlleron, H, Denti, P, Cohn, S, Mashabela, F, Hoffmann, JD, Shembe, S, Msandiwa, R, Wiesner, L, Velaphi, S, Lala, SG, Chaisson, RE, Martinson, N, Dooley, KE, Letutu, M, Raedani, S, Waja, Z, Hoffmann, C, Hull, J, Baliram, Y & on behalf of the Tshepiso Study Team 2017, 'Prevention of TB using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants' Journal of Antimicrobial Chemotherapy, vol 72, no. 7, dkx112, pp. 2028-2034. DOI: 10.1093/jac/dkx112
McIlleron H, Denti P, Cohn S, Mashabela F, Hoffmann JD, Shembe S et al. Prevention of TB using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants. Journal of Antimicrobial Chemotherapy. 2017 Jul 1;72(7):2028-2034. dkx112. Available from, DOI: 10.1093/jac/dkx112
McIlleron, Helen ; Denti, Paolo ; Cohn, Silvia ; Mashabela, Fildah ; Hoffmann, Jennifer D. ; Shembe, Saba ; Msandiwa, Regina ; Wiesner, Lubbe ; Velaphi, Sithembiso ; Lala, Sanjay G. ; Chaisson, Richard E. ; Martinson, Neil ; Dooley, Kelly E. ; Letutu, Matebogu ; Raedani, Susan ; Waja, Ziyaad ; Hoffmann, Chris ; Hull, Jenny ; Baliram, Yudesh ; on behalf of the Tshepiso Study Team. / Prevention of TB using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants. In: Journal of Antimicrobial Chemotherapy. 2017 ; Vol. 72, No. 7. pp. 2028-2034
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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 6months or rifampicin plus isoniazid for 3months (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.",
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T1 - Prevention of TB using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants

AU - McIlleron,Helen

AU - Denti,Paolo

AU - Cohn,Silvia

AU - Mashabela,Fildah

AU - Hoffmann,Jennifer D.

AU - Shembe,Saba

AU - Msandiwa,Regina

AU - Wiesner,Lubbe

AU - Velaphi,Sithembiso

AU - Lala,Sanjay G.

AU - Chaisson,Richard E.

AU - Martinson,Neil

AU - Dooley,Kelly E.

AU - Letutu,Matebogu

AU - Raedani,Susan

AU - Waja,Ziyaad

AU - Hoffmann,Chris

AU - Hull,Jenny

AU - Baliram,Yudesh

AU - on behalf of the Tshepiso Study Team

PY - 2017/7/1

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N2 - 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 6months or rifampicin plus isoniazid for 3months (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.

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