The prevention of HIV acquisition has been transformed over the last decade with the introduction of pre-exposure prophylaxis (PrEP), in which at-risk HIV uninfected individuals take antiretroviral medications daily to prevent infection.
UB Principal Investigator: Sarahmona Przybyla, PhD, MPH
Co-Principal Investigators: Charles Venuto, PhD (University of Rochester)
Funding Agency: University of Rochester Center for AIDS Research
Period: 4/2017 – 3/2018
Abstract: The prevention of HIV acquisition has been transformed over the last decade with the introduction of pre-exposure prophylaxis (PrEP), in which at-risk HIV uninfected individuals take antiretroviral medications daily to prevent infection. The efficacy of PrEP with oral tenofovir disproxil fumarate/emtricitabine (TDF/FTC) to prevent HIV acquisition has been demonstrated in multiple trials, and PrEP with TDF/FTC is now broadly recommended by the Center for Disease Control and Prevention and the World Health Organization. The adherence to PrEP is a key determinant of the exposure and efficacy of TDF/FTC. Therapeutic drug monitoring using single plasma concentrations of antiretrovirals for management of HIV-infected individuals may be considered in select clinical scenarios but is limited by a small window of exposure and is subject to significant day-to-day variation making it unsuitable to understand long-term adherence behaviors in PrEP users. In contrast, drug concentrations in hair reflect the uptake from the systemic circulation over weeks to months, thus making it possible to assess long-term adherence and average drug exposure over extended periods. The measurement of intracellular tenofovir diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs) has been used as a long-term measure of exposure in previous studies, however, hair levels offer several advantages in terms of utility. Therefore, we propose to develop methods to extract and analyze concentrations of tenofovir from hair in the context of PrEP. We believe this research intersects with the HIV/AIDS High Research Priority Topic on reducing incidence of HIV/AIDS by focusing on improving the tools to monitor adherence to PrEP. Furthermore, this could improve adherence by having the ability to design individualized and potentially less burdensome PrEP regimens based quantitatively on cumulative drug exposure estimates. The specific aim of this proposal is to develop a liquid chromatography tandem mass spectrometry-based assay that quantifies tenofovir concentrations in hair samples. In collaboration with the University at Buffalo CFAR Shared Pharmacology Resource Laboratory, we will develop and validate a UPLC-MS/MS method to measure tenofovir in hair.