Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention

Anthony T Podany, Yajing Bao, Susan Swindells, Richard E. Chaisson, Janet W. Andersen, Thando Mwelase, Khuanchai Supparatpinyo, Lerato Mohapi, Amita Gupta, Constance A. Benson, Peter Kim, Courtney V Fletcher

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Abstract

Background. Concomitant use of rifamycins to treat or prevent tuberculosis can result in subtherapeutic concentrations of antiretroviral drugs. We studied the interaction of efavirenz with daily rifapentine and isoniazid in human immunodeficiency virus (HIV)-infected individuals receiving a 4-week regimen to prevent tuberculosis. Methods. Participants receiving daily rifapentine and isoniazid with efavirenz had pharmacokinetic evaluations at baseline and weeks 2 and 4 of concomitant therapy. Efavirenz apparent oral clearance was estimated and the geometric mean ratio (GMR) of values before and during rifapentine and isoniazid was calculated. HIV type 1 (HIV-1) RNA was measured at baseline and week 8. Results. Eighty-seven participants were evaluable: 54% were female, and the median age was 35 years (interquartile range [IQR], 29-44 years). Numbers of participants with efavirenz concentrations ?1 mg/L were 85 (98%) at week 0; 81 (93%) at week 2; 78 (90%) at week 4; and 75 (86%) at weeks 2 and 4. Median efavirenz apparent oral clearance was 9.3 L/hour (IQR, 6.42-13.22 L/hour) at baseline and 9.8 L/hour (IQR, 7.04-15.59 L/hour) during rifapentine/isoniazid treatment (GMR, 1.04 [90% confidence interval,. 97-1.13]). Seventy-nine of 85 (93%) participants had undetectable HIV-1 RNA (<40 copies/mL) at entry; 71 of 75 (95%) participants had undetectable HIV-1 RNA at week 8. Two participants with undetectable HIV-1 RNA at study entry were detectable (43 and 47 copies/mL) at week 8. Conclusions. The proportion of participants with midinterval efavirenz concentrations ?1 mg/L did not cross below the prespecified threshold of >80%, and virologic suppression was maintained. Four weeks of daily rifapentine plus isoniazid can be coadministered with efavirenz without clinically meaningful reductions in efavirenz mid-dosing concentrations or virologic suppression.

Original languageEnglish (US)
Pages (from-to)1322-1327
Number of pages6
JournalClinical Infectious Diseases
Volume61
Issue number8
DOIs
StatePublished - Oct 15 2015

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rifapentine
efavirenz
Isoniazid
Tuberculosis
Pharmacokinetics
HIV
HIV-1
Rifamycins
RNA

Keywords

  • HIV/AIDS
  • Pharmacodynamics
  • Pharmacokinetics
  • Rifapentine
  • Tuberculosis

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention. / Podany, Anthony T; Bao, Yajing; Swindells, Susan; Chaisson, Richard E.; Andersen, Janet W.; Mwelase, Thando; Supparatpinyo, Khuanchai; Mohapi, Lerato; Gupta, Amita; Benson, Constance A.; Kim, Peter; Fletcher, Courtney V.

In: Clinical Infectious Diseases, Vol. 61, No. 8, 15.10.2015, p. 1322-1327.

Research output: Contribution to journalArticle

Podany, Anthony T ; Bao, Yajing ; Swindells, Susan ; Chaisson, Richard E. ; Andersen, Janet W. ; Mwelase, Thando ; Supparatpinyo, Khuanchai ; Mohapi, Lerato ; Gupta, Amita ; Benson, Constance A. ; Kim, Peter ; Fletcher, Courtney V. / Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention. In: Clinical Infectious Diseases. 2015 ; Vol. 61, No. 8. pp. 1322-1327.
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title = "Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention",
abstract = "Background. Concomitant use of rifamycins to treat or prevent tuberculosis can result in subtherapeutic concentrations of antiretroviral drugs. We studied the interaction of efavirenz with daily rifapentine and isoniazid in human immunodeficiency virus (HIV)-infected individuals receiving a 4-week regimen to prevent tuberculosis. Methods. Participants receiving daily rifapentine and isoniazid with efavirenz had pharmacokinetic evaluations at baseline and weeks 2 and 4 of concomitant therapy. Efavirenz apparent oral clearance was estimated and the geometric mean ratio (GMR) of values before and during rifapentine and isoniazid was calculated. HIV type 1 (HIV-1) RNA was measured at baseline and week 8. Results. Eighty-seven participants were evaluable: 54{\%} were female, and the median age was 35 years (interquartile range [IQR], 29-44 years). Numbers of participants with efavirenz concentrations ?1 mg/L were 85 (98{\%}) at week 0; 81 (93{\%}) at week 2; 78 (90{\%}) at week 4; and 75 (86{\%}) at weeks 2 and 4. Median efavirenz apparent oral clearance was 9.3 L/hour (IQR, 6.42-13.22 L/hour) at baseline and 9.8 L/hour (IQR, 7.04-15.59 L/hour) during rifapentine/isoniazid treatment (GMR, 1.04 [90{\%} confidence interval,. 97-1.13]). Seventy-nine of 85 (93{\%}) participants had undetectable HIV-1 RNA (<40 copies/mL) at entry; 71 of 75 (95{\%}) participants had undetectable HIV-1 RNA at week 8. Two participants with undetectable HIV-1 RNA at study entry were detectable (43 and 47 copies/mL) at week 8. Conclusions. The proportion of participants with midinterval efavirenz concentrations ?1 mg/L did not cross below the prespecified threshold of >80{\%}, and virologic suppression was maintained. Four weeks of daily rifapentine plus isoniazid can be coadministered with efavirenz without clinically meaningful reductions in efavirenz mid-dosing concentrations or virologic suppression.",
keywords = "HIV/AIDS, Pharmacodynamics, Pharmacokinetics, Rifapentine, Tuberculosis",
author = "Podany, {Anthony T} and Yajing Bao and Susan Swindells and Chaisson, {Richard E.} and Andersen, {Janet W.} and Thando Mwelase and Khuanchai Supparatpinyo and Lerato Mohapi and Amita Gupta and Benson, {Constance A.} and Peter Kim and Fletcher, {Courtney V}",
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T1 - Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention

AU - Podany, Anthony T

AU - Bao, Yajing

AU - Swindells, Susan

AU - Chaisson, Richard E.

AU - Andersen, Janet W.

AU - Mwelase, Thando

AU - Supparatpinyo, Khuanchai

AU - Mohapi, Lerato

AU - Gupta, Amita

AU - Benson, Constance A.

AU - Kim, Peter

AU - Fletcher, Courtney V

PY - 2015/10/15

Y1 - 2015/10/15

N2 - Background. Concomitant use of rifamycins to treat or prevent tuberculosis can result in subtherapeutic concentrations of antiretroviral drugs. We studied the interaction of efavirenz with daily rifapentine and isoniazid in human immunodeficiency virus (HIV)-infected individuals receiving a 4-week regimen to prevent tuberculosis. Methods. Participants receiving daily rifapentine and isoniazid with efavirenz had pharmacokinetic evaluations at baseline and weeks 2 and 4 of concomitant therapy. Efavirenz apparent oral clearance was estimated and the geometric mean ratio (GMR) of values before and during rifapentine and isoniazid was calculated. HIV type 1 (HIV-1) RNA was measured at baseline and week 8. Results. Eighty-seven participants were evaluable: 54% were female, and the median age was 35 years (interquartile range [IQR], 29-44 years). Numbers of participants with efavirenz concentrations ?1 mg/L were 85 (98%) at week 0; 81 (93%) at week 2; 78 (90%) at week 4; and 75 (86%) at weeks 2 and 4. Median efavirenz apparent oral clearance was 9.3 L/hour (IQR, 6.42-13.22 L/hour) at baseline and 9.8 L/hour (IQR, 7.04-15.59 L/hour) during rifapentine/isoniazid treatment (GMR, 1.04 [90% confidence interval,. 97-1.13]). Seventy-nine of 85 (93%) participants had undetectable HIV-1 RNA (<40 copies/mL) at entry; 71 of 75 (95%) participants had undetectable HIV-1 RNA at week 8. Two participants with undetectable HIV-1 RNA at study entry were detectable (43 and 47 copies/mL) at week 8. Conclusions. The proportion of participants with midinterval efavirenz concentrations ?1 mg/L did not cross below the prespecified threshold of >80%, and virologic suppression was maintained. Four weeks of daily rifapentine plus isoniazid can be coadministered with efavirenz without clinically meaningful reductions in efavirenz mid-dosing concentrations or virologic suppression.

AB - Background. Concomitant use of rifamycins to treat or prevent tuberculosis can result in subtherapeutic concentrations of antiretroviral drugs. We studied the interaction of efavirenz with daily rifapentine and isoniazid in human immunodeficiency virus (HIV)-infected individuals receiving a 4-week regimen to prevent tuberculosis. Methods. Participants receiving daily rifapentine and isoniazid with efavirenz had pharmacokinetic evaluations at baseline and weeks 2 and 4 of concomitant therapy. Efavirenz apparent oral clearance was estimated and the geometric mean ratio (GMR) of values before and during rifapentine and isoniazid was calculated. HIV type 1 (HIV-1) RNA was measured at baseline and week 8. Results. Eighty-seven participants were evaluable: 54% were female, and the median age was 35 years (interquartile range [IQR], 29-44 years). Numbers of participants with efavirenz concentrations ?1 mg/L were 85 (98%) at week 0; 81 (93%) at week 2; 78 (90%) at week 4; and 75 (86%) at weeks 2 and 4. Median efavirenz apparent oral clearance was 9.3 L/hour (IQR, 6.42-13.22 L/hour) at baseline and 9.8 L/hour (IQR, 7.04-15.59 L/hour) during rifapentine/isoniazid treatment (GMR, 1.04 [90% confidence interval,. 97-1.13]). Seventy-nine of 85 (93%) participants had undetectable HIV-1 RNA (<40 copies/mL) at entry; 71 of 75 (95%) participants had undetectable HIV-1 RNA at week 8. Two participants with undetectable HIV-1 RNA at study entry were detectable (43 and 47 copies/mL) at week 8. Conclusions. The proportion of participants with midinterval efavirenz concentrations ?1 mg/L did not cross below the prespecified threshold of >80%, and virologic suppression was maintained. Four weeks of daily rifapentine plus isoniazid can be coadministered with efavirenz without clinically meaningful reductions in efavirenz mid-dosing concentrations or virologic suppression.

KW - HIV/AIDS

KW - Pharmacodynamics

KW - Pharmacokinetics

KW - Rifapentine

KW - Tuberculosis

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