Common clinical conditions-age, low BMI, ritonavir use, mild renal impairment-affect tenofovir pharmacokinetics in a large cohort of HIV-infected women

Sanjiv M. Baxi, Ruth M. Greenblatt, Peter Bacchetti, Rebecca Scherzer, Howard Minkoff, Yong Huang, Kathryn Anastos, Mardge Cohen, Stephen J. Gange, Mary Young, Michael G. Shlipak, Monica Gandhi

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Objective: Tenofovir is used commonly in HIV treatment and prevention settings, but factors that correlate with tenofovir exposure in real-world settings are unknown. Design: Intensive pharmacokinetic studies of tenofovir in a large, diverse cohort of HIVinfected women over 24 h at steady state were performed and factors that influenced exposure [assessed by areas under the concentration-time curves (AUCs)] identified. Methods: HIV-infected women (n1/4101) on tenofovir-based therapy underwent intensive 24-h pharmacokinetic sampling. Data on race/ethnicity, age, exogenous steroid use, menstrual cycle phase, concomitant medications, recreational drugs and/or tobacco, hepatic and renal function, weight, and BMI were collected. Multivariable models using forward stepwise selection identified factors associated with effects on AUC. Glomerular filtration rates (GFRs) prior to starting tenofovir were estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using both creatinine and cystatin-C measures. Results: The median (range) of tenofovir AUCs was 3350 (1031-13 911) ngxh/ml. Higher AUCs were associated with concomitant ritonavir use (1.33-fold increase, P=0.002), increasing age (1.21-fold increase per decade, P=0.0007), and decreasing BMI (1.04-fold increase per 10% decrease in BMI). When GFR was calculated using cystatin-C measures, mild renal insufficiency prior to tenofovir initiation was associated with higher subsequent exposure (1.35-fold increasewhen pre-tenofovirGFR 70ml/min, P=0.0075). Conclusion: Concomitant ritonavir use, increasing age, decreasing BMI, and lower GFR prior to tenofovir initiation as estimated by cystatin C were all associated with elevated tenofovir exposure in a diverse cohort of HIV-infected women. Clinicians treating HIV-infected women should be aware of common clinical conditions that affect tenofovir exposure when prescribing this medication.

Original languageEnglish (US)
Pages (from-to)59-66
Number of pages8
JournalAIDS
Volume28
Issue number1
DOIs
StatePublished - Jan 2 2014

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Tenofovir
Ritonavir
Pharmacokinetics
HIV
Kidney
Cystatin C
Glomerular Filtration Rate

Keywords

  • Areas under the concentration-time curve
  • Cystatin C
  • Diverse populations
  • Exposure
  • Glomerular filtration rate
  • HIV-infected women
  • Pharmacokinetics
  • Tenofovir

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases
  • Medicine(all)

Cite this

Common clinical conditions-age, low BMI, ritonavir use, mild renal impairment-affect tenofovir pharmacokinetics in a large cohort of HIV-infected women. / Baxi, Sanjiv M.; Greenblatt, Ruth M.; Bacchetti, Peter; Scherzer, Rebecca; Minkoff, Howard; Huang, Yong; Anastos, Kathryn; Cohen, Mardge; Gange, Stephen J.; Young, Mary; Shlipak, Michael G.; Gandhi, Monica.

In: AIDS, Vol. 28, No. 1, 02.01.2014, p. 59-66.

Research output: Contribution to journalArticle

Baxi, SM, Greenblatt, RM, Bacchetti, P, Scherzer, R, Minkoff, H, Huang, Y, Anastos, K, Cohen, M, Gange, SJ, Young, M, Shlipak, MG & Gandhi, M 2014, 'Common clinical conditions-age, low BMI, ritonavir use, mild renal impairment-affect tenofovir pharmacokinetics in a large cohort of HIV-infected women', AIDS, vol. 28, no. 1, pp. 59-66. https://doi.org/10.1097/QAD.0000000000000033
Baxi, Sanjiv M. ; Greenblatt, Ruth M. ; Bacchetti, Peter ; Scherzer, Rebecca ; Minkoff, Howard ; Huang, Yong ; Anastos, Kathryn ; Cohen, Mardge ; Gange, Stephen J. ; Young, Mary ; Shlipak, Michael G. ; Gandhi, Monica. / Common clinical conditions-age, low BMI, ritonavir use, mild renal impairment-affect tenofovir pharmacokinetics in a large cohort of HIV-infected women. In: AIDS. 2014 ; Vol. 28, No. 1. pp. 59-66.
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abstract = "Objective: Tenofovir is used commonly in HIV treatment and prevention settings, but factors that correlate with tenofovir exposure in real-world settings are unknown. Design: Intensive pharmacokinetic studies of tenofovir in a large, diverse cohort of HIVinfected women over 24 h at steady state were performed and factors that influenced exposure [assessed by areas under the concentration-time curves (AUCs)] identified. Methods: HIV-infected women (n1/4101) on tenofovir-based therapy underwent intensive 24-h pharmacokinetic sampling. Data on race/ethnicity, age, exogenous steroid use, menstrual cycle phase, concomitant medications, recreational drugs and/or tobacco, hepatic and renal function, weight, and BMI were collected. Multivariable models using forward stepwise selection identified factors associated with effects on AUC. Glomerular filtration rates (GFRs) prior to starting tenofovir were estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using both creatinine and cystatin-C measures. Results: The median (range) of tenofovir AUCs was 3350 (1031-13 911) ngxh/ml. Higher AUCs were associated with concomitant ritonavir use (1.33-fold increase, P=0.002), increasing age (1.21-fold increase per decade, P=0.0007), and decreasing BMI (1.04-fold increase per 10{\%} decrease in BMI). When GFR was calculated using cystatin-C measures, mild renal insufficiency prior to tenofovir initiation was associated with higher subsequent exposure (1.35-fold increasewhen pre-tenofovirGFR 70ml/min, P=0.0075). Conclusion: Concomitant ritonavir use, increasing age, decreasing BMI, and lower GFR prior to tenofovir initiation as estimated by cystatin C were all associated with elevated tenofovir exposure in a diverse cohort of HIV-infected women. Clinicians treating HIV-infected women should be aware of common clinical conditions that affect tenofovir exposure when prescribing this medication.",
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T1 - Common clinical conditions-age, low BMI, ritonavir use, mild renal impairment-affect tenofovir pharmacokinetics in a large cohort of HIV-infected women

AU - Baxi, Sanjiv M.

AU - Greenblatt, Ruth M.

AU - Bacchetti, Peter

AU - Scherzer, Rebecca

AU - Minkoff, Howard

AU - Huang, Yong

AU - Anastos, Kathryn

AU - Cohen, Mardge

AU - Gange, Stephen J.

AU - Young, Mary

AU - Shlipak, Michael G.

AU - Gandhi, Monica

PY - 2014/1/2

Y1 - 2014/1/2

N2 - Objective: Tenofovir is used commonly in HIV treatment and prevention settings, but factors that correlate with tenofovir exposure in real-world settings are unknown. Design: Intensive pharmacokinetic studies of tenofovir in a large, diverse cohort of HIVinfected women over 24 h at steady state were performed and factors that influenced exposure [assessed by areas under the concentration-time curves (AUCs)] identified. Methods: HIV-infected women (n1/4101) on tenofovir-based therapy underwent intensive 24-h pharmacokinetic sampling. Data on race/ethnicity, age, exogenous steroid use, menstrual cycle phase, concomitant medications, recreational drugs and/or tobacco, hepatic and renal function, weight, and BMI were collected. Multivariable models using forward stepwise selection identified factors associated with effects on AUC. Glomerular filtration rates (GFRs) prior to starting tenofovir were estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using both creatinine and cystatin-C measures. Results: The median (range) of tenofovir AUCs was 3350 (1031-13 911) ngxh/ml. Higher AUCs were associated with concomitant ritonavir use (1.33-fold increase, P=0.002), increasing age (1.21-fold increase per decade, P=0.0007), and decreasing BMI (1.04-fold increase per 10% decrease in BMI). When GFR was calculated using cystatin-C measures, mild renal insufficiency prior to tenofovir initiation was associated with higher subsequent exposure (1.35-fold increasewhen pre-tenofovirGFR 70ml/min, P=0.0075). Conclusion: Concomitant ritonavir use, increasing age, decreasing BMI, and lower GFR prior to tenofovir initiation as estimated by cystatin C were all associated with elevated tenofovir exposure in a diverse cohort of HIV-infected women. Clinicians treating HIV-infected women should be aware of common clinical conditions that affect tenofovir exposure when prescribing this medication.

AB - Objective: Tenofovir is used commonly in HIV treatment and prevention settings, but factors that correlate with tenofovir exposure in real-world settings are unknown. Design: Intensive pharmacokinetic studies of tenofovir in a large, diverse cohort of HIVinfected women over 24 h at steady state were performed and factors that influenced exposure [assessed by areas under the concentration-time curves (AUCs)] identified. Methods: HIV-infected women (n1/4101) on tenofovir-based therapy underwent intensive 24-h pharmacokinetic sampling. Data on race/ethnicity, age, exogenous steroid use, menstrual cycle phase, concomitant medications, recreational drugs and/or tobacco, hepatic and renal function, weight, and BMI were collected. Multivariable models using forward stepwise selection identified factors associated with effects on AUC. Glomerular filtration rates (GFRs) prior to starting tenofovir were estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using both creatinine and cystatin-C measures. Results: The median (range) of tenofovir AUCs was 3350 (1031-13 911) ngxh/ml. Higher AUCs were associated with concomitant ritonavir use (1.33-fold increase, P=0.002), increasing age (1.21-fold increase per decade, P=0.0007), and decreasing BMI (1.04-fold increase per 10% decrease in BMI). When GFR was calculated using cystatin-C measures, mild renal insufficiency prior to tenofovir initiation was associated with higher subsequent exposure (1.35-fold increasewhen pre-tenofovirGFR 70ml/min, P=0.0075). Conclusion: Concomitant ritonavir use, increasing age, decreasing BMI, and lower GFR prior to tenofovir initiation as estimated by cystatin C were all associated with elevated tenofovir exposure in a diverse cohort of HIV-infected women. Clinicians treating HIV-infected women should be aware of common clinical conditions that affect tenofovir exposure when prescribing this medication.

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KW - Cystatin C

KW - Diverse populations

KW - Exposure

KW - Glomerular filtration rate

KW - HIV-infected women

KW - Pharmacokinetics

KW - Tenofovir

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