Within the context of chronic HIV infection, pulmonary arterial hypertension (PAH) is a life-threatening complication characterized by pulmonary vascular remodeling, elevated pulmonary arterial pressure and right heart failure. Lack of understanding of the pathogenesis of HIV-PAH, along with deficiencies of available animal models, greatly impede identification and testing of new therapies. In this proposal, the overall objectives will focus on 1) determination of the role of chronic immune activation and inflammation on the development of PAH in a non-human primate model of HIV-PAH and 2) the evaluation of the effectiveness of anti-retroviral therapy, conventional PAH therapy and anti-inflammatory therapy in the primate model. These studies will not only address the mechanisms associated with the development of HIV-PAH, but they will provide critical information regarding the timing and targets that may be amenable to therapies aimed at both prevention and resolution of vascular damage, hemodynamic alterations and right heart dysfunction.

Public Health Relevance

Within the context of chronic HIV infection, pulmonary arterial hypertension (PAH) is a life-threatening complication characterized by pulmonary vascular remodeling, elevated pulmonary arterial pressure and right heart failure. Lack of understanding of the pathogenesis of HIV-PAH, along with deficiencies of available animal models, greatly impede identification and testing of new therapies. In this proposal, the overall objectives will focus on 1) determination of the role of chronic immune activation and inflammation on the development of PAH in a non-human primate model of HIV-PAH and 2) the evaluation of the effectiveness of anti-retroviral therapy, conventional PAH therapy and anti-inflammatory therapy in the primate model. These studies will not only address the mechanisms associated with the development of HIV-PAH, but they will provide critical information regarding the timing and targets that may be amenable to therapies aimed at both prevention and resolution of vascular damage, hemodynamic alterations and right heart dysfunction.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
High Priority, Short Term Project Award (R56)
Project #
1R56HL126525-01
Application #
8915900
Study Section
Special Emphasis Panel (ZHL1-CSR-B (S2))
Program Officer
Caler, Elisabet V
Project Start
2014-09-03
Project End
2015-08-31
Budget Start
2014-09-03
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$761,352
Indirect Cost
$261,357
Name
University of Pittsburgh
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213