Abstract # 13204 Event # 138:

Scheduled for Friday, August 10, 2018 02:15 PM-02:30 PM: (Chula Vista ) Oral Presentation


TRAINING MONKEYS TO TAKE A BITTER PILL: USING POSITIVE REINFORCEMENT TO DELIVER ANTIRETROVIRAL THERAPY MEDICATIONS TO AWAKE RHESUS MONKEYS (MACACA MULATTA)

J. L. Weed1, M. B. Daly1,2,3, A. M. Clayton1, J. P. Jolly1, B. Skinner1 and J. G. Garcia-Lerma1,2,3
1Centers for Disease Control and Prevention, CMB/DSR, National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA 30329, USA, 2Laboratory Branch, Division of HIV/AIDS Prevention, 3National Center for HIV, Hepatitis, STD, and TB Prevention
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     Human immunodeficiency virus (HIV) is a significant global health issue. Although not curative, daily oral antiretroviral (ARV) therapy has significantly reduced HIV/AIDS-related morbidity and mortality. Non-human primates (NHPs) are valuable models to evaluate HIV persistence during ARV treatment. However, mimicking daily human ARV administration in NHPs is difficult due to the bitterness of medications. We developed a procedure to administer tenofovir alafenamide (TAF) and emtricitabine (FTC) using positive reinforcement training (PRT). Ten rhesus macaques were trained to take clinically relevant doses of FTC (20 mg/kg) and TAF (1.5 mg/kg) daily for a month. Of these animals, 40% took FTC/TAF with 100% adherence. We objectively measured adherence by quantifying intracellular TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) in peripheral blood mononuclear cells (PBMCs) and rectal and lymphoid tissues. Levels of TFV-DP (median=884 fmol/million cells; range, 771-913) and FTC-TP (median=381 fmol/million cells; range, 349-413) in PBMCs were stable over time (p=.922; p=.895, respectively) and within the range achieved with daily dosing in humans. Drug levels in rectal and lymphoid tissues were also high and within the expected range. By combining observational and biochemical analysis, we demonstrated that PRT is effective for delivering ARVs to macaques in a reliable manner. Our approach using clinically relevant drug doses administered orally refines animal models of HIV infection/ARV treatment and paves the way for studies aimed at evaluating HIV persistence during ARV therapy.