TY - JOUR
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.
N1 - Funding Information:
Potential conflicts of interest. R. M. G. has received payment previously for manuscript preparation from HRSA and all authors have received funding from the National Institutes of Health. All other authors: no conflicts.
Funding Information:
Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID RO1-AI-65233) with data collected in the Women’s Interagency HIV Study (WIHS). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The WIHS is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding for WIHS is also provided by the National Center for Research Resources (UCSF - CTSI Grant UL1 RR024131). M. G. was additionally supported by a Mentored Patient-Oriented Research Career Development Award (K23 A1067065) from NIAID.
PY - 2011/5/15
Y1 - 2011/5/15
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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U2 - 10.1093/cid/cir131
DO - 10.1093/cid/cir131
M3 - Article
C2 - 21507924
AN - SCOPUS:79955450039
SN - 1058-4838
VL - 52
SP - 1267
EP - 1275
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 10
ER -