Protease inhibitor levels in hair strongly predict virologic response to treatment.
OBJECTIVE
Antiretroviral (ARV) therapies fail when behavioral or biologic factors lead to inadequate medication exposure. The currently available methods to assess ARV exposure are limited. Levels of ARVs in hair reflect plasma concentrations over weeks to months, and may provide a novel method for predicting therapeutic responses.


METHODS
The Women's Interagency HIV Study, a prospective cohort of HIV-infected women, provided the basis for developing and assessing methods to measure commonly prescribed protease inhibitors (lopinavir/ritonavir and atazanavir) in small hair samples. We examined the association between hair protease inhibitor levels and initial virologic responses to therapy in multivariate logistic regression models.


RESULTS
ARV concentrations in hair were strongly and independently associated with treatment response for 224 women starting a new protease inhibitor-based regimen. For participants initiating lopinavir/ritonavir, the odds ratio (OR) for virologic suppression was 39.8 [95% confidence interval (CI) = 2.8-564] for those with lopinavir hair levels in the top tertile (>1.9 ng/mg) compared to the bottom (</=0.41 ng/mg) when controlling for self-reported adherence, age, race, starting viral load and CD4 cell count, and prior experience with protease inhibitors. For women starting atazanavir, the adjusted OR for virologic success was 7.7 (95% CI = 2.0-29.7) for those with hair concentrations in the top tertile (>3.4 ng/mg) compared to the lowest (</=1.2 ng/mg).


CONCLUSIONS
Protease inhibitor levels in small hair samples were the strongest independent predictor of virologic success in a diverse group of HIV-infected adults. This non-invasive method for determining ARV exposure may have particular relevance for the epidemic in resource-poor settings due to the ease of collecting and storing hair.
Gandhi
Monica
M
Department of Medicine, University of California, San Francisco, San Francisco, California, USA. monica.gandhi@ucsf.edu
Ameli
Niloufar
N
Bacchetti
Peter
P
Gange
Stephen J
SJ
Anastos
Kathryn
K
Levine
Alexandra
A
Hyman
Charles L
CL
Cohen
Mardge
M
Young
Mary
M
Huang
Yong
Y
Greenblatt
Ruth M
RM
D000328:Adult; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D016903:Drug Monitoring / Q000379:methods; D004812:Epidemiologic Methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006197:Hair / Q000378:metabolism*; D006801:Humans; D061466:Lopinavir; D008875:Middle Aged; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000627:therapeutic use; D010349:Patient Compliance; D011725:Pyridines / Q000493:pharmacokinetics / Q000627:therapeutic use; D011744:Pyrimidinones / Q000493:pharmacokinetics / Q000627:therapeutic use; D019438:Ritonavir / Q000493:pharmacokinetics / Q000627:therapeutic use; D013048:Specimen Handling / Q000379:methods; D016896:Treatment Outcome; D019562:Viral Load
D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D019438:Ritonavir