Antiretroviral Drug Penetration in HIV Reservoir Sites using Tissue from Deceased Donors
Reduction of persistent HIV-infected cells in reservoir tissues is essential towards HIV cure. It is difficult to measure tissue penetration of therapeutics (antiretrovirals, ARVs, and curative agents) in many of these sites (e.g. brain, cardiac, lung tissue) due to the inability to sample these tissues in living people. Leveraging postmortem tissue banked at UCSF from deceased people with HIV (PWH), we will determine ARV penetration in these tissue reservoir sites, and determine if there is a link between ARV exposure to size the viral reservoir in each tissue. Specifically we will develop novel analytical assays to quantify tenofovir (Aim 1), emtricitabine (Aim 2), and their associated intracellular metabolites in postmortem brain, gastrointestinal, heart, lung, lymphoid tissue, and blood. Tissue penetration relative to blood levels will be assessed for each drug and tissue. We will test whether tissue ARV levels correlate with viral reservoirs present in the same tissue. This study will likely be the first of its kind to evaluate ARV levels in brain, cardiac, and lung tissue and their association with viral reservoir levels in those same tissues. Further, the developed assays will serve as a model for extraction of other small molecules including other therapeutics (including those for treatment of cardiovascular, metabolic, and psychological conditions) as well as biomarkers inflammation or disease related processes in the context of HIV.