Atazanavir concentration in hair is the strongest predictor of outcomes on antiretroviral therapy

Monica Gandhi, Niloufar Ameli, Peter Bacchetti, Kathryn Anastos, Stephen J. Gange, Howard Minkoff, Mary Young, Joel Milam, Mardge H. Cohen, Gerald B. Sharp, Yong Huang, Ruth M. Greenblatt

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Background. Adequate exposure to antiretrovirals is important to maintain durable responses, but methods to assess exposure (eg, querying adherence and single plasma drug level measurements) are limited. Hair concentrations of antiretrovirals can integrate adherence and pharmacokinetics into a single assay. Methods. Small hair samples were collected from participants in the Women's Interagency HIV Study (WIHS), a large cohort of human immunodeficiency virus (HIV)-infected (and at-risk noninfected) women. From 2003 through 2008, we analyzed atazanavir hair concentrations longitudinally for women reporting receipt of atazanavir-based therapy. Multivariate random effects logistic regression models for repeated measures were used to estimate the association of hair drug levels with the primary outcome of virologic suppression (HIV RNA level, <80 copies/mL). Results. 424 WIHS participants (51% African-American, 31% Hispanic) contributed 1443 person-visits to the analysis. After adjusting for age, race, treatment experience, pretreatment viral load, CD4 count and AIDS status, and self-reported adherence, hair levels were the strongest predictor of suppression. Categorized hair antiretroviral levels revealed a monotonic relationship to suppression; women with atazanavir levels in the highest quintile had odds ratios (ORs) of 59.8 (95% confidence ratio, 29.0-123.2) for virologic suppression. Hair atazanavir concentrations were even more strongly associated with resuppression of viral loads in subgroups in which there had been previous lapses in adherence (OR, 210.2 [95% CI, 46.0-961.1]), low hair levels (OR, 132.8 [95% CI, 26.5-666.0]), or detectable viremia (OR, 400.7 [95% CI, 52.3-3069.7]). Conclusions. Antiretroviral hair levels surpassed any other predictor of virologic outcomes to HIV treatment in a large cohort. Low antiretroviral exposure in hair may trigger interventions prior to failure or herald virologic failure in settings where measurement of viral loads is unavailable. Monitoring hair antiretroviral concentrations may be useful for prolonging regimen durability.

Original languageEnglish (US)
Pages (from-to)1267-1275
Number of pages9
JournalClinical Infectious Diseases
Volume52
Issue number10
DOIs
StatePublished - May 15 2011

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Hair
HIV
Viral Load
Odds Ratio
Therapeutics
Atazanavir Sulfate
Logistic Models
Viremia
CD4 Lymphocyte Count
Hispanic Americans
Pharmaceutical Preparations
African Americans
Acquired Immunodeficiency Syndrome
Pharmacokinetics
RNA

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)

Cite this

Gandhi, M., Ameli, N., Bacchetti, P., Anastos, K., Gange, S. J., Minkoff, H., ... Greenblatt, R. M. (2011). Atazanavir concentration in hair is the strongest predictor of outcomes on antiretroviral therapy. Clinical Infectious Diseases, 52(10), 1267-1275. https://doi.org/10.1093/cid/cir131

Atazanavir concentration in hair is the strongest predictor of outcomes on antiretroviral therapy. / Gandhi, Monica; Ameli, Niloufar; Bacchetti, Peter; Anastos, Kathryn; Gange, Stephen J.; Minkoff, Howard; Young, Mary; Milam, Joel; Cohen, Mardge H.; Sharp, Gerald B.; Huang, Yong; Greenblatt, Ruth M.

In: Clinical Infectious Diseases, Vol. 52, No. 10, 15.05.2011, p. 1267-1275.

Research output: Contribution to journalArticle

Gandhi, M, Ameli, N, Bacchetti, P, Anastos, K, Gange, SJ, Minkoff, H, Young, M, Milam, J, Cohen, MH, Sharp, GB, Huang, Y & Greenblatt, RM 2011, 'Atazanavir concentration in hair is the strongest predictor of outcomes on antiretroviral therapy', Clinical Infectious Diseases, vol. 52, no. 10, pp. 1267-1275. https://doi.org/10.1093/cid/cir131
Gandhi, Monica ; Ameli, Niloufar ; Bacchetti, Peter ; Anastos, Kathryn ; Gange, Stephen J. ; Minkoff, Howard ; Young, Mary ; Milam, Joel ; Cohen, Mardge H. ; Sharp, Gerald B. ; Huang, Yong ; Greenblatt, Ruth M. / Atazanavir concentration in hair is the strongest predictor of outcomes on antiretroviral therapy. In: Clinical Infectious Diseases. 2011 ; Vol. 52, No. 10. pp. 1267-1275.
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abstract = "Background. Adequate exposure to antiretrovirals is important to maintain durable responses, but methods to assess exposure (eg, querying adherence and single plasma drug level measurements) are limited. Hair concentrations of antiretrovirals can integrate adherence and pharmacokinetics into a single assay. Methods. Small hair samples were collected from participants in the Women's Interagency HIV Study (WIHS), a large cohort of human immunodeficiency virus (HIV)-infected (and at-risk noninfected) women. From 2003 through 2008, we analyzed atazanavir hair concentrations longitudinally for women reporting receipt of atazanavir-based therapy. Multivariate random effects logistic regression models for repeated measures were used to estimate the association of hair drug levels with the primary outcome of virologic suppression (HIV RNA level, <80 copies/mL). Results. 424 WIHS participants (51{\%} African-American, 31{\%} Hispanic) contributed 1443 person-visits to the analysis. After adjusting for age, race, treatment experience, pretreatment viral load, CD4 count and AIDS status, and self-reported adherence, hair levels were the strongest predictor of suppression. Categorized hair antiretroviral levels revealed a monotonic relationship to suppression; women with atazanavir levels in the highest quintile had odds ratios (ORs) of 59.8 (95{\%} confidence ratio, 29.0-123.2) for virologic suppression. Hair atazanavir concentrations were even more strongly associated with resuppression of viral loads in subgroups in which there had been previous lapses in adherence (OR, 210.2 [95{\%} CI, 46.0-961.1]), low hair levels (OR, 132.8 [95{\%} CI, 26.5-666.0]), or detectable viremia (OR, 400.7 [95{\%} CI, 52.3-3069.7]). Conclusions. Antiretroviral hair levels surpassed any other predictor of virologic outcomes to HIV treatment in a large cohort. Low antiretroviral exposure in hair may trigger interventions prior to failure or herald virologic failure in settings where measurement of viral loads is unavailable. Monitoring hair antiretroviral concentrations may be useful for prolonging regimen durability.",
author = "Monica Gandhi and Niloufar Ameli and Peter Bacchetti and Kathryn Anastos and Gange, {Stephen J.} and Howard Minkoff and Mary Young and Joel Milam and Cohen, {Mardge H.} and Sharp, {Gerald B.} and Yong Huang and Greenblatt, {Ruth M.}",
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T1 - Atazanavir concentration in hair is the strongest predictor of outcomes on antiretroviral therapy

AU - Gandhi, Monica

AU - Ameli, Niloufar

AU - Bacchetti, Peter

AU - Anastos, Kathryn

AU - Gange, Stephen J.

AU - Minkoff, Howard

AU - Young, Mary

AU - Milam, Joel

AU - Cohen, Mardge H.

AU - Sharp, Gerald B.

AU - Huang, Yong

AU - Greenblatt, Ruth M.

PY - 2011/5/15

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N2 - Background. Adequate exposure to antiretrovirals is important to maintain durable responses, but methods to assess exposure (eg, querying adherence and single plasma drug level measurements) are limited. Hair concentrations of antiretrovirals can integrate adherence and pharmacokinetics into a single assay. Methods. Small hair samples were collected from participants in the Women's Interagency HIV Study (WIHS), a large cohort of human immunodeficiency virus (HIV)-infected (and at-risk noninfected) women. From 2003 through 2008, we analyzed atazanavir hair concentrations longitudinally for women reporting receipt of atazanavir-based therapy. Multivariate random effects logistic regression models for repeated measures were used to estimate the association of hair drug levels with the primary outcome of virologic suppression (HIV RNA level, <80 copies/mL). Results. 424 WIHS participants (51% African-American, 31% Hispanic) contributed 1443 person-visits to the analysis. After adjusting for age, race, treatment experience, pretreatment viral load, CD4 count and AIDS status, and self-reported adherence, hair levels were the strongest predictor of suppression. Categorized hair antiretroviral levels revealed a monotonic relationship to suppression; women with atazanavir levels in the highest quintile had odds ratios (ORs) of 59.8 (95% confidence ratio, 29.0-123.2) for virologic suppression. Hair atazanavir concentrations were even more strongly associated with resuppression of viral loads in subgroups in which there had been previous lapses in adherence (OR, 210.2 [95% CI, 46.0-961.1]), low hair levels (OR, 132.8 [95% CI, 26.5-666.0]), or detectable viremia (OR, 400.7 [95% CI, 52.3-3069.7]). Conclusions. Antiretroviral hair levels surpassed any other predictor of virologic outcomes to HIV treatment in a large cohort. Low antiretroviral exposure in hair may trigger interventions prior to failure or herald virologic failure in settings where measurement of viral loads is unavailable. Monitoring hair antiretroviral concentrations may be useful for prolonging regimen durability.

AB - Background. Adequate exposure to antiretrovirals is important to maintain durable responses, but methods to assess exposure (eg, querying adherence and single plasma drug level measurements) are limited. Hair concentrations of antiretrovirals can integrate adherence and pharmacokinetics into a single assay. Methods. Small hair samples were collected from participants in the Women's Interagency HIV Study (WIHS), a large cohort of human immunodeficiency virus (HIV)-infected (and at-risk noninfected) women. From 2003 through 2008, we analyzed atazanavir hair concentrations longitudinally for women reporting receipt of atazanavir-based therapy. Multivariate random effects logistic regression models for repeated measures were used to estimate the association of hair drug levels with the primary outcome of virologic suppression (HIV RNA level, <80 copies/mL). Results. 424 WIHS participants (51% African-American, 31% Hispanic) contributed 1443 person-visits to the analysis. After adjusting for age, race, treatment experience, pretreatment viral load, CD4 count and AIDS status, and self-reported adherence, hair levels were the strongest predictor of suppression. Categorized hair antiretroviral levels revealed a monotonic relationship to suppression; women with atazanavir levels in the highest quintile had odds ratios (ORs) of 59.8 (95% confidence ratio, 29.0-123.2) for virologic suppression. Hair atazanavir concentrations were even more strongly associated with resuppression of viral loads in subgroups in which there had been previous lapses in adherence (OR, 210.2 [95% CI, 46.0-961.1]), low hair levels (OR, 132.8 [95% CI, 26.5-666.0]), or detectable viremia (OR, 400.7 [95% CI, 52.3-3069.7]). Conclusions. Antiretroviral hair levels surpassed any other predictor of virologic outcomes to HIV treatment in a large cohort. Low antiretroviral exposure in hair may trigger interventions prior to failure or herald virologic failure in settings where measurement of viral loads is unavailable. Monitoring hair antiretroviral concentrations may be useful for prolonging regimen durability.

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