Sildenafil to Treat HIV-Associated Pulmonary Hypertension

You may not be if

• For Healthy Volunteers:
• 1. Males or females, 18 years of age or older.
• 2. No history of HIV infection.
• 3. EKG and echocardiogram with no evidence of clinical relevant heart disease (including TRV less than 2.5 m/s)
• 4. No history of causes of pulmonary hypertension such as collagen vascular disease, chronic liver disease with ALT or AST greater than 2 times the upper limit of normal or cirrhosis of the liver, chronic thromboembolic disease, congenital heart defects, or pulmonary parenchymal disease with hypoxemia.
• 5. No history of diseases thought to be related to development of endothelial dysfunction including systemic hypertension or diabetes requiring drug therapy, hypercholesterolemia and obesity.
• 6. No history of anemia, thrombocytopenia or coagulopathy.
• 7. No history of renal insufficiency.
• 8. No medical conditions requiring chronic medication use with the exception of:
• 1. Heartburn, GERD
• 2. Environmental allegeries, post nasal drip or non-allergic rhinitis
• 3. Asthma with no history of oral steroid use, weekly inhaled steroids, or hospitalization for asthma exacerbation.
• 4. Dermatologic conditions that do not require the use of oral steroids or other immunosuppressants.
• 9. No more than 20 cigarettes per year for the previous 2 years and no cigarette use for 30 days prior to the screening evaluation until completion of the study.
• For HIV Positive Volunteers:
• 1. Males or females, 18 years of age or older.
• 2. Diagnosis of HIV infection.
• 3. Under the care of a primary care physician.
• 4. No history of other potential causes of pulmonary hypertension such as collagen vascular disease, chronic liver disease with ALT or AST greater than 2 times the upper limit of normal or cirrhosis of the liver, chronic thromboembolic disease, congenital heart defects, or pulmonary parenchymal disease with hypoxemia.
• 5. For stage 3 enrollment: symptomatic pulmonary hypertension with MPAP greater than or equal to 25 mmHg and six-minute walk distance between 150-450 m.
• For Healthy volunteers:
• 1. Current pregnancy, lactation or women not currently using medically acceptable birth control. (All women of childbearing age will be required to have a screening urine or blood pregnancy test)
• 2. Contraindication to MRI scanning including individuals with the following devices:
• A) Central nervous system aneurysm clips
• B) Implanted neural stimulator
• C) Implanted cardiac pacemaker or defibrillator prior to enrollment
• D) Cochlear implant
• E) Ocular foreign body (e.g. metal shavings)
• F) Insulin pump
• G) Metal shrapnel or bullet
• 3. Contraindications to MRI contrast agent administration:
• 4. Inability to provide informed written consent for participation in the study.
• 5. Chronic, medically refractory atrial tachyarrhythmias
• 6. Symptoms of heart failure
• 7. Mean PA greater than 25 mmHg or PVR greater than 1.5 wood units, or PCWP greater than 15 mmHg
• 8. History of recreational drug use with the exception of marijuana. No Marijuana use within 3 months of protocol screening through completion of the study.
• Volunteers may be excluded if in the opinion of the study investigators they have a condition that may adversely affect the outcome of the study or the safety of the volunteer.
• For HIV Positive Volunteers:
• 1. Current pregnancy, lactation or women not currently using medically acceptable birth control.
• 2. Active, untreated opportunistic infection with the exception of oral thrush or neoplasm with the exception of Kaposi's Sarcoma.
• 3. Any of the following medical conditions:
• A) Severe renal insufficiency (on hemodialysis or serum creatinine greater than 2.5 mg/dl) or (CrCl less than 20 ml/min).
• B) Severe coagulopathy (platelets less than 100,000, PT INR greater than 1.5, PTT greater than 40 s)
• 4. Chronic, medically refractory atrial tachyarrhythmias
• 5. Current recreational drug use or use within 4 weeks of protocol screening with the exception of marijuana
• 6. Contraindication to MRI scanning including individuals with the following devices:
• A) Central nervous system aneurysm clips
• B) Implanted neural stimulator
• C) Implanted cardiac pacemaker or defibrillator prior to enrollment
• D) Cochlear implant
• E) Ocular foreign body (e.g. metal shavings)
• F) Insulin pump
• G) Metal shrapnel or bullet
• 7. Contraindications to MRI contrast agent administration:
• A) Individuals with hemoglobinopathies
• Volunteers may be excluded if in the opinion of the study investigators they have a condition that may adversely affect the outcome of the study or the safety of the volunteer.