Abstract 20195: Longitudinal Assessment of Hemodynamic Changes in a NonHuman Primate Model of Human Immunodeficiency Virus Associated Pulmonary Arterial Hypertension

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Introduction: Pulmonary arterial hypertension (PAH) is a life-threatening disease with higher incidence in HIV-infected versus non-infected individuals. Non-human primates (NHP) infected with simian immunodeficiency virus (SIV) develop clinical manifestations of HIV infection, including pulmonary hypertension.

Objective: To characterize the development and progression of PAH and determine the relationship of hemodynamic changes to clinical characteristics associated with SIV-PAH.

Methods and Results: Serial right heart catheterizations and echocardiographic imaging were performed pre- and post-SIV infection on rhesus macaques (n=22). At 6 months post infection (mpi), 9 animals (41%) had mean pulmonary arterial pressures (mPAP) of at least 25mmHg and elevated right heart pressures. Of the NHP with increased pulmonary pressures at 6 mpi, 55% (n=6) exhibited continued increase at 12 mpi (progressive PAH) while 45% (n=5) had reduced pressures at 12 mpi (transient PAH). Echocardiographic analyses indicated evidence of diastolic right ventricular (RV) dysfunction. RV involvement in early disease progression was also evident by increases in RV glucose uptake in PAH+ macaques, as measured by positron emission coupled computed tomography (PET-CT). RV and pulmonary vascular collagen deposition was significantly elevated in PAH+ animals compared with non-PAH animals. Viral load and CD4 T cell levels were not predictive of PAH development or progression.

Conclusion: Hemodynamic derangement occurs in a subset of SIV-infected macaques as early as 6 mpi. RV systolic function matches afterload in this model, indicating adaptive RV function in the context of early stage disease. Diastolic RV dysfunction is present, suggesting this as an early sign of disease. Development of SIV-PAH is not directly associated with either plasma viral load or CD4 T cell levels, suggesting indirect mechanisms of pathogenesis.

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