Statins for Pulmonary and Cardiac Complications of Chronic HIV - Coordinating Center

Growing evidence indicates that chronic obstructive pulmonary disease (COPD) is an important cause of respiratory impairment in HIV+ persons and will likely increase as the HIV+ population continues to age. In the HIV-uninfected population, COPD frequently co-exists with cardiac disease including atherosclerosis and pulmonary hypertension (PH). The investigators work has demonstrated that a syndrome of "cardiopulmonary dysfunction" exists even in non-smoking or antiretroviral-treated HIV+ individuals. The investigators have found that HIV+ individuals have a high prevalence of respiratory symptoms, airflow obstruction, and diffusing capacity (DLco) abnormalities that occur concurrently with cardiac co-morbidities, including radiographic measures of atherosclerosis and elevated echocardiographic pulmonary artery pressures. This syndrome is marked by inflammation with elevated levels of cytokines and hsCRP, peripheral T-cell activation, and increased sputum neutrophils as well as elevation of NT-proBNP, a marker of heart strain. Importantly, the investigators have shown that DLco impairment and elevated NT-proBNP are significant independent predictors of mortality in HIV, indicating that cardiopulmonary dysfunction is likely highly clinically relevant and identifies a vulnerable population in whom the investigators lack effective interventions.

Statins have anti-inflammatory effects in the lung and vasculature that might benefit cardiopulmonary dysfunction in HIV. These agents have a long history of clinical use in cardiovascular disease and are currently being investigated as disease-modifying drugs for HIV, COPD, and PH. In preliminary analyses, the investigators have found that HIV+ individuals who received statin therapy within the past year were significantly less likely to have impaired DLco and had lower pulmonary artery pressures, lower NT-proBNP, lower peripheral cytokines, and fewer sputum neutrophils despite being older and having a greater smoking history than those not using statins.

Inclusion criteria

• HIV-1 infection, documented in medical record at any time prior to study entry.
• Men and women age18 years to 80 years.
• Presence of COPD (FEV1/FVC<0.70 or DLco≤80% predicted)
• No lipid-lowering medication (prescription or non-prescription) within 60 days prior to study entry. This includes all statin drugs, omega-3-fatty acids/fish oil (if dose > 1 g/day), red yeast rice (any dose), and niacin products (e.g., niacin, nicotinic acid, vitamin B3; if dose of >100 mg/day)
• Normal liver and kidney function test at screening visit:
• Liver function: ALT 7 to 55 U/L; AST 8 to 48 U/L; ALP 45 to 115 U/L; Bilirubin 0.1 to 1.0 mg/dL; GGT 9 to 48 U/L; LDH 122 to 222 umol/L; PT 8.3 to 10.8 seconds
• Kidney function: BUN 8-20 mg/dl. Creatinine 0.8-1.2 mg/dl for males and 0.6-0.9 mg/dl for females. GFR normal results range from 90 - 120 mL/min/1.73 m2.) Participants will be on a stable ART regimen (i.e. no change in agents) with either suppressed HIV viral level or <50 viral level for at least 3 months.
• If smoker, not planning on quitting smoking during the study period. If non-smoker, not planning on starting smoking during the study period.
• Able to provide informed consent.
• Able to participate in study procedures based on the investigator's assessment.
• For women of reproductive potential, negative urine pregnancy test and willingness to use birth control during study period (see Contraception requirements).
• Ability and willingness to complete all tests.
• Participant in MACS, Women's Interagency Health Study, or Attendee of UPMC HIV / AIDS Program.

Exclusion criteria

• Pregnancy or breast-feeding.
• Known allergy/sensitivity or any hypersensitivity to HMG CoA reductase inhibitors, prior history of myopathy, rhabdomyolysis, or intolerance of statin therapy.
• Currently receiving a statin or should be taking a statin based on clinical criteria.
• Concurrent use of Coumadin.
• History of liver disease.
• Contraindication to pulmonary function testing (i.e. abdominal or cataract surgery within 3 months, recent myocardial infarction, etc.).
• Diagnosis of asthma with normal diffusing capacity.
• History of diabetes mellitus requiring medication of hemoglobin A1C>6.5% on screening laboratories.
• Increasing respiratory symptoms or febrile (temperature >100.40F [380C]) within 4 weeks of study entry.
• Hospitalization within 4 weeks prior to study entry.
• Use of antibiotics within 4 weeks of study entry.
• Uncontrolled hypertension at screening visit (systolic > 160 mm Hg or diastolic > 100 mm Hg) from an average of two or more readings. Subject may return for screening after blood pressure is controlled.
• Active cancer requiring systemic chemotherapy or radiation.
• Active infection of lungs, brain, or abdomen.
• Use of anti-inflammatory agents (such as aspirin), immunomodulators (e.g., interleukins, interferons, cyclosporine) or immunosuppressive medications within 60 days prior to study entry. Routine vaccinations are allowed if administered at least 7 days prior to study entry.
• Use of azole antifungals, erythromycin, or amiodarone.
• More than weekly use of magnesium hydroxide.
• The intention to quit smoking during the study period.
• Alcoholism defined as >35 drinks per week or that will impair ability to complete study investigations in the opinion of the investigator.
• Active (within the past 6 months) intravenous drug use or that will impair ability to complete study investigations in the opinion of the investigator.
• Use of other investigational agents within 90 days of study entry or planning on entering another therapy trial during study period.
• No use of inhaled corticosteroids (beta-agonists are allowed).
• Viral load above 50 in past 3 months.