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

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.

Figures

Figure 1.

Hair collection procedure for antiretroviral levels: Picture demonstrates the isolation of the 20-strand hair thatch from the occipital region of the head (left panel) and the cutting of the hair thatch right at the scalp (right panel).

Figure 2.

Percent of person-visits in each hair quintile where viral load suppressed (entire study sample) and odds ratio of virologic response per hair quintile (univariate relationship): ATV, atazanavir.

Figure 3.

Percent of person-visits in each hair quintile in which viral load was suppressed for 3 subgroups in which “failure” was previously revealed (Figure 3A: subgroup 1; Figure 3B: subgroup 2; Figure 3C: subgroup 3). ATV, atazanavir.

Figure 4.

Possible algorithm for use of atazanavir hair levels in the clinical setting. ATV, atazanavir.