Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-2 (of 2 Records) |
Query Trace: Clayton AM [original query] |
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Training rhesus macaques to take daily oral antiretroviral therapy for preclinical evaluation of HIV prevention and treatment strategies
Daly MB , Clayton AM , Ruone S , Mitchell J , Dinh C , Holder A , Jolly J , Garcia-Lerma JG , Weed JL . PLoS One 2019 14 (11) e0225146 BACKGROUND: Macaque models of simian or simian/human immunodeficiency virus (SIV or SHIV) infection are critical for the evaluation of antiretroviral (ARV)-based HIV treatment and prevention strategies. However, modelling human oral ARV administration is logistically challenging and fraught by limited adherence. Here, we developed a protocol for administering daily oral doses of ARVs to macaques with a high rate of compliance. METHODS: Parameters of positive reinforcement training (PRT), behavioral responses and optimal drug delivery foods were defined in 7 male rhesus macaques (Macaca mulatta). Animals were trained to sit in a specified cage location prior to receiving ARVs, emtricitabine (FTC) and tenofovir alafenamide (TAF), in a blended food mixture, which was followed immediately with a juice chaser. Consistency of daily oral adherence was evaluated in 4 trained macaques receiving clinically equivalent doses of FTC and TAF (20 and 1.5 mg/kg, respectively) in a short-term (1 month) and an extended (6 month) trial. Adherence was monitored using medication diaries and by quantifying intracellular FTC-triphosphate (FTC-TP) and tenofovir-diphosphate (TFV-DP) concentrations in peripheral mononuclear blood cells (PBMCs). RESULTS: Trained macaques quickly and consistently took daily oral ARVs for 1 month with an average 99.8% observed adherence. Intracellular concentrations of TFV-DP (median = 845.8 fmol/million cells [range, 620.8-1031.3]) and FTC-TP (median = 367.0 fmol/million cells [range, 289.5-413.5) in PBMCs were consistent with high adherence. Extended treatment with select subjects yielded similar observations for three months (99.5% adherence, 352/356 complete doses taken), although a sudden drop in adherence was observed after splenic biopsy surgery. CONCLUSIONS: We demonstrate that trained macaques reliably adhere to a daily oral ARV regimen, although unexpected adherence issues are possible. Our approach, using clinical doses of oral FTC and TAF daily, further refines macaque models of HIV treatment and prevention by mimicking the human route and timing of ARV administration. |
Development of an occupational risk assessment tool for laboratory animal facilities
Clayton AM , Hayes J , Lathrop GW , Powell N . Appl Biosaf 2019 24 (2) 72-82 Introduction: Laboratory animal facilities aim to provide excellence in animal care and welfare and support scientific research. Critical to these goals is to ensure a safe work environment for personnel comprising veterinary and animal care, laboratory research, and maintenance staff. Objective: Thus, performing occupational risk assessments allows for evaluation of risks from identified hazards associated with a variety of tasks ongoing in laboratory animal facilities. Methods: Herein, we present the development of an occupational risk assessment tool purposed to capture the dynamics of work performed in laboratory animal facilities, calculate and prioritize identified risks associated with procedures and processes, and inform and evaluate risk mitigations. Results: We also discuss a risk assessment for refining sharps use in nonhuman primate husbandry and care to demonstrate the utility of this tool to improve occupational safety in our animal facility. Conclusion: This tool and framework evolve into a holistic occupational risk management system that identifies, evaluates, and mitigates occupational risks; determines risk acceptability; consistently ensures communication and consultation with frontline personnel, stakeholders, senior leadership, and subject matter experts in biosafety, science, and animal care and welfare; and continuously strives to improve and enhance the operations of laboratory animal facilities. |
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