Effect of Rosuvastatin on Cardiovascular Risk in HIV-Infected Individuals With Low High Density Lipoprotein (HDL) Cholesterol

Condition(s) targeted: HIV Infections; Cardiovascular Disease

Intervention: rosuvastatin (Drug)

Phase: Phase 2/Phase 3

Status: Not yet recruiting

Sponsored by: University of Hawaii

Official(s) and/or principal investigator(s):
Cecilia Shikuma, MD, Principal Investigator, Affiliation: Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii

Overall contact:
Debra Ogata-Arakaki, RN, Phone: 808 737-2751, Ext: 503, Email: ogataara@hawaii.edu

Rosuvastatin belongs to a class of medications commonly called "statins" which are medications given for high low density lipoprotein (LDL) 'bad' cholesterol to prevent atherosclerosis (hardening of blood vessels) and lower risk of heart attacks and other circulation problems. Recent studies in the general non-HIV infected population have shown that the beneficial effect of statins in preventing circulation problems is larger than would be expected from lowering of LDL-cholesterol alone. It has been suggested that the additional beneficial effect of statins may be due to the anti-inflammatory effect of statins.

The risk of heart attacks and other circulation problems may be high in HIV infected individuals. This may be due to the inflammatory stress effects of HIV. The main purpose of the study is to see if rosuvastatin will have a beneficial effect on the circulatory system in HIV infected individuals even in those who do not have high LDL cholesterol levels. Therefore, in HIV-infected individuals with normal or low LDL cholesterol levels but with evidence of low HDL cholesterol levels which may be a sign of low grade inflammation, the study will look at whether 6 months of rosuvastatin will lead to improvement in brachial artery flow-mediated dilatation (FMD), a marker of early atherosclerosis (hardening of the blood vessels).

Official title: Randomized Pilot Study of the Effect of Low-Dose Rosuvastatin on Endothelial Function, Oxidative Stress and Inflammatory Parameters in HIV-Infected Individuals With Low HDL Cholesterol Levels and Low to Normal LDL Cholesterol Levels

Study design: Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study

Primary outcome: Change in flow mediated dilatation (FMD) of the brachial artery

Secondary outcome:

Change in HIV biomarkers of immune activation to include CD38 and CD69 expression on T cells and CD16 and CD69 expression on monocytes

Change in mitochondrial-specific oxidative stress (mt-specific 8-oxo-dG) and oxidative phosphorylation (OXPHOS) protein/enzyme activity [Complex I and Complex IV] levels

Change in glucose homeostasis and insulin resistance as assessed by oral glucose tolerance testing

Change in total, trunk, and peripheral fat by dual energy absorptiometry (DXA)

Change in total, HDL and LDL cholesterol and triglyceride levels

Change in coronary calcium scores by CT

Occurrence of adverse side effects [as assessed by NIH Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (Dec. 2004)]

Change in hsCRP

Minimum age: 40 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- HIV infection

- Age > 40 years old

- On stable antiretroviral therapy for > 6 months with no plans to change therapy

during the randomized treatment phase of the study

- Plasma HIV RNA < 50 copies/mL

- Karnofsky performance score > 70 within 30 days prior to study entry

- Ability to understand and sign informed consent

- Following laboratory values obtained within 30 days prior to randomization:

- Absolute neutrophil count (ANC) > 750/mm3

- Hemoglobin > 8. 0 g/dL

- Platelets > 50,000/mm3

- ALT (SGPT) and AST (SGOT) < 2. 5 x ULN

- Fasting glucose < 126 mg/dL

- TSH < 3. 0 mIU/L

- HDL-C < 40 mg/dL in men, < 50 mg/dL in women

- Direct LDL-C < 130 mg/dL

- Calculated creatinine clearance > 50 mL/min

- Willing to be treated with rosuvastatin or be on an observational arm for a minimum

of 6 months

- Female subject must not participate in a conception process (active attempt to become

pregnant) or be post-menopausal. If participating in sexual activity that could lead to pregnancy, the subject must use contraception while receiving study medication and 30 days after stopping the medication

Exclusion criteria

- History of past cardiovascular event

- Acute illnesses or active AIDS-defining opportunistic infection (OI) within 30 days

prior to entry

- Other chronic illness including diabetes, autoimmune diseases, and endocrinopathies

- Serology positive for hepatitis B surface antigen or hepatitis C antibody

- Signs and symptoms of liver failure

- Receipt of supraphysiologic glucocorticoid therapy within 3 months prior to study

entry

- Use of lipid lowering agents within 30 days prior to study entry

- Receipt of an HIV vaccine or investigational agents

- Pregnancy or breast-feeding

- Presence of any active malignancy within the last 5 years

- Severe Hypertension (Systolic >/= 180 or Diastolic >/= 110 mm Hg)

- Use of oral postmenopausal hormone replacement therapy

- Known hypersensitivity to rosuvastatin

- Active drug or alcohol dependence

- Any acute illness within 30 days prior to study entry that, in the opinion of the

site investigator, would interfere with participation in the study.

- Use of lopinavir/ritonavir (Kaletra) as part of current HIV antiretroviral regimen

Debra Ogata-Arakaki, RN, Phone: 808 737-2751, Ext: 503, Email: ogataara@hawaii.edu

Hawaii Center for AIDS, Honolulu, Hawaii 96816, United States

Starting date: September 2009
Ending date: December 2011
Last updated: September 29, 2009