High Intensity Lipid Lowering Following Acute Coronary Syndromes for Persons Living With HIV

HILLCLIMBER is a randomized, controlled, open-label phase II trial of moderate dose statin
therapy versus high-dose statin therapy in HIV-infected persons taking antiretroviral therapy
(ART) who have coronary heart disease (CHD).

All subjects will have an initial 2-week run-in period with pravastatin 40mg daily (Week 0 to
2). Subjects not demonstrating significant toxicity at week 2 will then be randomized to
rosuvastatin 20mg (high intensity dose group) versus continuing pravastatin 40mg daily
(moderate intensity group) for 12 weeks (Weeks 2 to 14). At week 6, those in the rosuvastatin
arm who do not demonstrate significant toxicity and whose LDL-c is >60mg/dl and decreased by
less than 25% compared with week 2 will then have doses increased to rosuvastatin 40mg.

Inclusion Criteria:

- HIV-1 infection

- HIV RNA below the lower limit of assay detection within 12 months of study entry

- Documented coronary heart disease (CHD): nonfatal MI, unrecognized MI, unstable angina
pectoris, and/or stable angina pectoris, as defined by the American Heart Association
Case Definitions for Acute Coronary Heart Disease in Epidemiology and Clinical
Research Studies

- Negative serum or urine pregnancy test

- Men and women age 18 to 75 years of age

Exclusion Criteria:

- Serious illness or AIDS-related complication within 21 days of screening requiring
systemic treatment and/or hospitalization

- No coronary heart disease (CHD).

- Not currently receiving antiretroviral therapy or taking any of the following
antiretroviral agents: atazanavir/ritonavir, lopinavir/ritonavir.

- History of statin intolerance leading to discontinuation, dose decrease, or change to
less potent dose equivalent

- Statin absolute contraindication

- Current use of atorvastatin 20mg daily or greater or rosuvastatin 10mg daily or
greater

- Chronic kidney disease stage 4 or greater (including dialysis)

- Systolic heart failure with last documented LVEF <35%

- Pregnant or breastfeeding

- Laboratory values obtained within 45 days prior to study entry:

LDL-c <80 mg/dl while not on statin or LDL-c <60 mg/dl while on statin ALT > 3 x Upper
Limit of Normal (ULN) AST > 3 x ULN Creatinine kinase (CK) >3 x ULN (calculated creatinine
clearance (CrCl) <50 mL/min, as estimated by the Cockcroft-Gault equation)

- Life expectancy <12 months

- Prior organ transplant

- Active malignancy

- Inflammatory muscle disease