Atazanavir Concentration in Hair Is the Strongest Predictor of Outcomes on Antiretroviral Therapy

Departments of Medicine, University of California, San Francisco, 94122, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 05/2011; 52(10):1267-75. DOI: 10.1093/cid/cir131
Source: PubMed


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.
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).
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]).
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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Available from: Yong Huang, Apr 02, 2014
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    • "Measuring ARV drug levels in hair is a promising approach for evaluating ART adherence in developing settings (Beumer, Bosman, & Maes, 2001; Gandhi, Yang, Bacchetti, & Huang, 2014; Hickey et al., 2014; Huang et al., 2008; Huang et al., 2011). Hair samples are simple to collect, can be stored at room temperature, and are processed without biohazardous precautions. "
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    ABSTRACT: Current tools for measuring medication adherence have significant limitations, especially among pediatric populations. We conducted a prospective observational study to assess the use of antiretroviral (ARV) drug levels in hair for evaluating antiretroviral therapy (ART) adherence among HIV-infected children in rural Uganda. Three-day caregiver recall, 30-day visual analog scale (VAS), Medication Event Monitoring System (MEMS), and unannounced pill counts and liquid formulation weights (UPC) were collected monthly over a one-year period. Hair samples were collected quarterly and analyzed for nevirapine (NVP) levels, and plasma HIV RNA levels were collected every six months. Among children with at least one hair sample collected, we used univariable random intercept linear regression models to compare log transformed NVP concentrations with each adherence measure, and the child's age, sex, and CD4 count percentage (CD4%). One hundred and twenty-one children aged 2-10 years were enrolled in the study; 74 (61%) provided at least one hair sample, and the mean number of hair samples collected per child was 1.9 (standard deviation [SD] 1.0). Three-day caregiver recall, VAS, and MEMS were found to be positively associated with increasing NVP concentration in hair, although associations were not statistically significant. UPC was found to have a nonsignificant negative association with increasing hair NVP concentration. In conclusion, NVP drug concentrations in hair were found to have nonsignificant, although generally positive, associations with other adherence measures in a cohort of HIV-infected children in Uganda. Hair collection in this population proved challenging, suggesting the need for community education and buy-in with the introduction of novel methodologies.
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    • "Several small thatches of hair (∼150–200 strands) were cut as close as possible to the scalp in the occipital region and/or pubic region, and the distal portion labeled [22]. The proximal section of the scalp or pubic hair sample (about 1.5 cm) was cut down and chopped to 1–2 mm length segments with scissors and 5 mg were weighed, processed and analyzed using liquid chromatography/tandem mass spectrometry (LC/MS-MS). "
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    • "An alternative, and less invasive procedure for obtaining at least some of these follicle cells, is plucking [58] [59]. Plucked hairs have been previously used as a surrogate tissue in the clinic for diagnostics [60] [61] [62] and a recent phase 1 clinical trial included the use of γ-H2AX detection in plucked eyebrow hair bulbs to confirm the effects of a PARP (Poly (ADP-ribose) polymerase) inhibitor in vivo [49]. Like plucked hairs, the use of exfoliative oral cells has been previously promoted as a non-invasive technique for cancer diagnosis [63] and for γ-H2AX detection [64] "
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