Nevirapine pharmacokinetics in HIV-infected persons receiving rifapentine and isoniazid for TB prevention

A. T. Podany; J. Leon-Cruz; J. Hakim; K. Supparatpinyo; A. Omoz-Oarhe; D. Langat; N. Mwelase; C. Kanyama; A. Gupta; C. A. Benson; R. E. Chaisson; S. Swindells; C. V. Fletcher; Peter Kim; Daniel Johnson; Laura Moran; Janet Andersen; Yajing Bao; Shirley Wu; Christina Blanchard-Horan; Ann Walawander; Katherine Shin; Ruth Ebiasah; David Holland; Marc Antoine Jeanjuste; Eric Nuermberger; Sandy Pillay; Ian Sanne; Janet Nicotera; David Shugarts; Amina Shali; Jimi Tutko; Brigitte Demers; Marilyn Maroni; Jorge L. Sanchez; David Iglesias; Javier Lama; Mitch Matoga; Guilherme Do Amaral Calvet; Ronald Kibet Tonui; Taolo Modise; Margaret Kasaro; Kogieleum Naidoo; Deelip Kadam; William Burman

doi:10.1093/jac/dkaa470

Nevirapine pharmacokinetics in HIV-infected persons receiving rifapentine and isoniazid for TB prevention

A. T. Podany, J. Leon-Cruz, J. Hakim, K. Supparatpinyo, A. Omoz-Oarhe, D. Langat, N. Mwelase, C. Kanyama, A. Gupta, C. A. Benson, R. E. Chaisson, S. Swindells, C. V. Fletcher, Peter Kim, Daniel Johnson, Laura Moran, Janet Andersen, Yajing Bao, Shirley Wu, Christina Blanchard-HoranAnn Walawander, Katherine Shin, Ruth Ebiasah, David Holland, Marc Antoine Jeanjuste, Eric Nuermberger, Sandy Pillay, Ian Sanne, Janet Nicotera, David Shugarts, Amina Shali, Jimi Tutko, Brigitte Demers, Marilyn Maroni, Jorge L. Sanchez, David Iglesias, Javier Lama, Mitch Matoga, Guilherme Do Amaral Calvet, Ronald Kibet Tonui, Taolo Modise, Margaret Kasaro, Kogieleum Naidoo, Deelip Kadam, William Burman

School of Medicine

Research output: Contribution to journal › Review article › peer-review

Abstract

Background: The use of rifamycin antibiotics for TB prevention carries a risk of detrimental drug-drug interactions with concomitantly used ART. Objectives: To evaluate the interaction of the antiretroviral drug nevirapine in combination with 4 weeks of daily rifapentine and isoniazid for TB prevention in people living with HIV. Methods: Participants were individuals enrolled in the BRIEF-TB study receiving nevirapine and randomized to the rifapentine/isoniazid arm of the study. Participants provided sparse pharmacokinetic (PK) sampling at baseline and weeks 2 and 4 for trough nevirapine determination. Nevirapine apparent oral clearance (CL/F) was estimated and the geometric mean ratio (GMR) of CL/F prior to and during rifapentine/isoniazid was calculated. Results: Seventy-eight participants had evaluable PK data: 61 (78%) female, 51 (65%) black non-Hispanic and median (range) age of 40 (13-66) years. Median (IQR) nevirapine trough concentrations were: Week 0, 7322 (5266-9302) ng/mL; week 2, 5537 (3552-8462) ng/mL; and week 4, 5388 (3516-8243) ng/mL. Sixty out of 78 participants (77%) had nevirapine concentrations ≥3000 ng/mL at both week 2 and 4. Median (IQR) nevirapine CL/F values were: Week 0 pre-rifapentine/isoniazid, 2.03 (1.58-2.58) L/h; and during rifapentine/isoniazid, 2.62 (1.81-3.42) L/h. The GMR (90% CI) for nevirapine CL/F was 1.30 (1.26-1.33). Conclusions: The CL/F of nevirapine significantly increased with concomitant rifapentine/isoniazid. The decrease in nevirapine trough concentrations during rifapentine/isoniazid therapy suggests induction of nevirapine metabolism, consistent with known rifapentine effects. The magnitude of this drug-drug interaction suggests daily rifapentine/isoniazid for TB prevention should not be co-administered with nevirapine-containing ART.

Original language	English (US)
Pages (from-to)	718-721
Number of pages	4
Journal	Journal of Antimicrobial Chemotherapy
Volume	76
Issue number	3
DOIs	https://doi.org/10.1093/jac/dkaa470
State	Published - Mar 1 2021

ASJC Scopus subject areas

Microbiology (medical)
Pharmacology (medical)
Infectious Diseases
Pharmacology

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10.1093/jac/dkaa470

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Podany, A. T., Leon-Cruz, J., Hakim, J., Supparatpinyo, K., Omoz-Oarhe, A., Langat, D., Mwelase, N., Kanyama, C., Gupta, A., Benson, C. A., Chaisson, R. E., Swindells, S., Fletcher, C. V., Kim, P., Johnson, D., Moran, L., Andersen, J., Bao, Y., Wu, S., ... Burman, W. (2021). Nevirapine pharmacokinetics in HIV-infected persons receiving rifapentine and isoniazid for TB prevention. Journal of Antimicrobial Chemotherapy, 76(3), 718-721. https://doi.org/10.1093/jac/dkaa470

Podany, AT, Leon-Cruz, J, Hakim, J, Supparatpinyo, K, Omoz-Oarhe, A, Langat, D, Mwelase, N, Kanyama, C, Gupta, A, Benson, CA, Chaisson, RE, Swindells, S, Fletcher, CV, Kim, P, Johnson, D, Moran, L, Andersen, J, Bao, Y, Wu, S, Blanchard-Horan, C, Walawander, A, Shin, K, Ebiasah, R, Holland, D, Jeanjuste, MA, Nuermberger, E, Pillay, S, Sanne, I, Nicotera, J, Shugarts, D, Shali, A, Tutko, J, Demers, B, Maroni, M, Sanchez, JL, Iglesias, D, Lama, J, Matoga, M, Do Amaral Calvet, G, Tonui, RK, Modise, T, Kasaro, M, Naidoo, K, Kadam, D & Burman, W 2021, 'Nevirapine pharmacokinetics in HIV-infected persons receiving rifapentine and isoniazid for TB prevention', Journal of Antimicrobial Chemotherapy, vol. 76, no. 3, pp. 718-721. https://doi.org/10.1093/jac/dkaa470

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title = "Nevirapine pharmacokinetics in HIV-infected persons receiving rifapentine and isoniazid for TB prevention",

abstract = "Background: The use of rifamycin antibiotics for TB prevention carries a risk of detrimental drug-drug interactions with concomitantly used ART. Objectives: To evaluate the interaction of the antiretroviral drug nevirapine in combination with 4 weeks of daily rifapentine and isoniazid for TB prevention in people living with HIV. Methods: Participants were individuals enrolled in the BRIEF-TB study receiving nevirapine and randomized to the rifapentine/isoniazid arm of the study. Participants provided sparse pharmacokinetic (PK) sampling at baseline and weeks 2 and 4 for trough nevirapine determination. Nevirapine apparent oral clearance (CL/F) was estimated and the geometric mean ratio (GMR) of CL/F prior to and during rifapentine/isoniazid was calculated. Results: Seventy-eight participants had evaluable PK data: 61 (78%) female, 51 (65%) black non-Hispanic and median (range) age of 40 (13-66) years. Median (IQR) nevirapine trough concentrations were: Week 0, 7322 (5266-9302) ng/mL; week 2, 5537 (3552-8462) ng/mL; and week 4, 5388 (3516-8243) ng/mL. Sixty out of 78 participants (77%) had nevirapine concentrations ≥3000 ng/mL at both week 2 and 4. Median (IQR) nevirapine CL/F values were: Week 0 pre-rifapentine/isoniazid, 2.03 (1.58-2.58) L/h; and during rifapentine/isoniazid, 2.62 (1.81-3.42) L/h. The GMR (90% CI) for nevirapine CL/F was 1.30 (1.26-1.33). Conclusions: The CL/F of nevirapine significantly increased with concomitant rifapentine/isoniazid. The decrease in nevirapine trough concentrations during rifapentine/isoniazid therapy suggests induction of nevirapine metabolism, consistent with known rifapentine effects. The magnitude of this drug-drug interaction suggests daily rifapentine/isoniazid for TB prevention should not be co-administered with nevirapine-containing ART.",

author = "Podany, {A. T.} and J. Leon-Cruz and J. Hakim and K. Supparatpinyo and A. Omoz-Oarhe and D. Langat and N. Mwelase and C. Kanyama and A. Gupta and Benson, {C. A.} and Chaisson, {R. E.} and S. Swindells and Fletcher, {C. V.} and Peter Kim and Daniel Johnson and Laura Moran and Janet Andersen and Yajing Bao and Shirley Wu and Christina Blanchard-Horan and Ann Walawander and Katherine Shin and Ruth Ebiasah and David Holland and Jeanjuste, {Marc Antoine} and Eric Nuermberger and Sandy Pillay and Ian Sanne and Janet Nicotera and David Shugarts and Amina Shali and Jimi Tutko and Brigitte Demers and Marilyn Maroni and Sanchez, {Jorge L.} and David Iglesias and Javier Lama and Mitch Matoga and {Do Amaral Calvet}, Guilherme and Tonui, {Ronald Kibet} and Taolo Modise and Margaret Kasaro and Kogieleum Naidoo and Deelip Kadam and William Burman",

year = "2021",

month = mar,

day = "1",

doi = "10.1093/jac/dkaa470",

language = "English (US)",

volume = "76",

pages = "718--721",

journal = "Journal of Antimicrobial Chemotherapy",

issn = "0305-7453",

publisher = "Oxford University Press",

number = "3",

}

TY - JOUR

T1 - Nevirapine pharmacokinetics in HIV-infected persons receiving rifapentine and isoniazid for TB prevention

AU - Podany, A. T.

AU - Leon-Cruz, J.

AU - Hakim, J.

AU - Supparatpinyo, K.

AU - Omoz-Oarhe, A.

AU - Langat, D.

AU - Mwelase, N.

AU - Kanyama, C.

AU - Gupta, A.

AU - Benson, C. A.

AU - Chaisson, R. E.

AU - Swindells, S.

AU - Fletcher, C. V.

AU - Kim, Peter

AU - Johnson, Daniel

AU - Moran, Laura

AU - Andersen, Janet

AU - Bao, Yajing

AU - Wu, Shirley

AU - Blanchard-Horan, Christina

AU - Walawander, Ann

AU - Shin, Katherine

AU - Ebiasah, Ruth

AU - Holland, David

AU - Jeanjuste, Marc Antoine

AU - Nuermberger, Eric

AU - Pillay, Sandy

AU - Sanne, Ian

AU - Nicotera, Janet

AU - Shugarts, David

AU - Shali, Amina

AU - Tutko, Jimi

AU - Demers, Brigitte

AU - Maroni, Marilyn

AU - Sanchez, Jorge L.

AU - Iglesias, David

AU - Lama, Javier

AU - Matoga, Mitch

AU - Do Amaral Calvet, Guilherme

AU - Tonui, Ronald Kibet

AU - Modise, Taolo

AU - Kasaro, Margaret

AU - Naidoo, Kogieleum

AU - Kadam, Deelip

AU - Burman, William

PY - 2021/3/1

Y1 - 2021/3/1

N2 - Background: The use of rifamycin antibiotics for TB prevention carries a risk of detrimental drug-drug interactions with concomitantly used ART. Objectives: To evaluate the interaction of the antiretroviral drug nevirapine in combination with 4 weeks of daily rifapentine and isoniazid for TB prevention in people living with HIV. Methods: Participants were individuals enrolled in the BRIEF-TB study receiving nevirapine and randomized to the rifapentine/isoniazid arm of the study. Participants provided sparse pharmacokinetic (PK) sampling at baseline and weeks 2 and 4 for trough nevirapine determination. Nevirapine apparent oral clearance (CL/F) was estimated and the geometric mean ratio (GMR) of CL/F prior to and during rifapentine/isoniazid was calculated. Results: Seventy-eight participants had evaluable PK data: 61 (78%) female, 51 (65%) black non-Hispanic and median (range) age of 40 (13-66) years. Median (IQR) nevirapine trough concentrations were: Week 0, 7322 (5266-9302) ng/mL; week 2, 5537 (3552-8462) ng/mL; and week 4, 5388 (3516-8243) ng/mL. Sixty out of 78 participants (77%) had nevirapine concentrations ≥3000 ng/mL at both week 2 and 4. Median (IQR) nevirapine CL/F values were: Week 0 pre-rifapentine/isoniazid, 2.03 (1.58-2.58) L/h; and during rifapentine/isoniazid, 2.62 (1.81-3.42) L/h. The GMR (90% CI) for nevirapine CL/F was 1.30 (1.26-1.33). Conclusions: The CL/F of nevirapine significantly increased with concomitant rifapentine/isoniazid. The decrease in nevirapine trough concentrations during rifapentine/isoniazid therapy suggests induction of nevirapine metabolism, consistent with known rifapentine effects. The magnitude of this drug-drug interaction suggests daily rifapentine/isoniazid for TB prevention should not be co-administered with nevirapine-containing ART.

AB - Background: The use of rifamycin antibiotics for TB prevention carries a risk of detrimental drug-drug interactions with concomitantly used ART. Objectives: To evaluate the interaction of the antiretroviral drug nevirapine in combination with 4 weeks of daily rifapentine and isoniazid for TB prevention in people living with HIV. Methods: Participants were individuals enrolled in the BRIEF-TB study receiving nevirapine and randomized to the rifapentine/isoniazid arm of the study. Participants provided sparse pharmacokinetic (PK) sampling at baseline and weeks 2 and 4 for trough nevirapine determination. Nevirapine apparent oral clearance (CL/F) was estimated and the geometric mean ratio (GMR) of CL/F prior to and during rifapentine/isoniazid was calculated. Results: Seventy-eight participants had evaluable PK data: 61 (78%) female, 51 (65%) black non-Hispanic and median (range) age of 40 (13-66) years. Median (IQR) nevirapine trough concentrations were: Week 0, 7322 (5266-9302) ng/mL; week 2, 5537 (3552-8462) ng/mL; and week 4, 5388 (3516-8243) ng/mL. Sixty out of 78 participants (77%) had nevirapine concentrations ≥3000 ng/mL at both week 2 and 4. Median (IQR) nevirapine CL/F values were: Week 0 pre-rifapentine/isoniazid, 2.03 (1.58-2.58) L/h; and during rifapentine/isoniazid, 2.62 (1.81-3.42) L/h. The GMR (90% CI) for nevirapine CL/F was 1.30 (1.26-1.33). Conclusions: The CL/F of nevirapine significantly increased with concomitant rifapentine/isoniazid. The decrease in nevirapine trough concentrations during rifapentine/isoniazid therapy suggests induction of nevirapine metabolism, consistent with known rifapentine effects. The magnitude of this drug-drug interaction suggests daily rifapentine/isoniazid for TB prevention should not be co-administered with nevirapine-containing ART.

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JF - Journal of Antimicrobial Chemotherapy

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Nevirapine pharmacokinetics in HIV-infected persons receiving rifapentine and isoniazid for TB prevention

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