Atorvastatin on Biomarkers of Inflammation, Coagulopathy, Angiogenesis & T-cells

Since people started taking HIV medications, illness from AIDS has decreased, but other
serious diseases like heart disease (heart attacks) and certain kinds of cancer have
increased. HIV causes inflammation (irritation) inside the body that cannot be felt but can
be measured by levels of certain inflammation blood tests. Inflammation may contribute to
diseases (such as heart attacks) that have become some of the leading causes of death in
people with HIV. HIV therapy can partially lower levels of inflammation measured in blood,
however, levels of inflammation in people who have HIV who are taking certain kinds of
anti-HIV drugs may remain high compared with those found in people not infected with HIV.

Inclusion Criteria:

- HIV-1 infected

- Combination ART that includes any boosted PI regimen for at least 6 months prior to
study entry

- No plans to change the antiretroviral regimen in the next year

- Must have been on the same HAART regimen for at least 12 weeks with no change prior
to study entry. More information on this criterion can be found in the study
protocol.

- If on vitamin D replacement therapy, must have been on stable regimen for ≥ 1 mo.
prior to study entry.

- CD4+ T-cell count obtained within 45 days prior to study entry at any laboratory that
has a Clinical Laboratory Improvement Amendments (CLIA) certification or its
equivalent.

- Screening HIV-1 RNA < 40 copies/mL by Abbott RealTime PCR at a laboratory certified
by the DAIDS Virology Quality Assurance (VQA) program within 45 days prior to study
entry.

- All known HIV-1 RNA levels obtained within 180 days prior to study entry are below
the limits of quantification on all tests, with documentation of at least 1 test by
any FDA-approved assay at a CLIA-certified laboratory obtained between 90 to 180 days
prior to study entry. A single RNA "blip" of < 500 copies/mL during this time period
was permissible if RNA levels immediately before and after were below the limits of
quantification for the assay.

- Laboratory values obtained within 45 days prior to study entry- Absolute neutrophil
count (ANC) 750/mm3, Hemoglobin ≥ 9.0 g/dL for female subjects,10.0 g/dL for male
subjects, Platelet count ≥ 100,000/mm3, Calculated creatinine clearance (CrCl) 30
mL/min, as estimated by the Cockcroft-Gault equation, Creatine kinase (CK) < 3 x ULN,
AST ≤ 2.0 x ULN, ALT ≤ 2.0 x ULN, Total bilirubin ≤ 2.5 x ULN. If the subject was
taking an indinavir- or atazanavir-containing regimen at the time of screening, a
total bilirubin of ≤ 5 x ULN is acceptable, Fasting LDL cholesterol ≥ 70 mg/dL and <
130 mg/dL, Fasting triglycerides < 400 mg/dL, Fasting glucose < 110 mg/dL

- Screening plasma D-dimer > 0.34 μg/mL from a sample obtained within 45 days prior to
study entry was the original D-dimer criterion. It was revised to ≥ 0.25 ug/mL four
months after the first enrollment, and subsequently the D-dimer eligibility criterion
was completely cut off a year later.

- For females of reproductive potential (women who had not been post-menopausal for at
least 24 consecutive months, i.e., who had menses within 24 months prior to study
entry), or women who had not undergone surgical sterilization, specifically
hysterectomy or bilateral oophorectomy or tubal ligation) required a negative serum
or urine pregnancy test within 48 hours prior to entry. More information on this
criterion can be found in the study protocol.

- Must agree not to participate in the conception process (e.g., active attempt to
become pregnant or to impregnate, sperm donation, in vitro fertilization), and if
participating in sexual activity that could lead to pregnancy, the subject/partner
must use at least 2 reliable methods of contraception, (condoms, without a
spermicidal agent; a diaphragm or cervical cap without spermicide; an IUD; or
hormone-based contraceptive), for 2 weeks before study treatment, while receiving
study treatment, and for 6 weeks after receiving study treatment. As hormone-based
contraceptives (oral, transdermal, or subdermal) can affect coagulopathy biomarkers,
subjects who plan on using such a contraceptive during the study must be taking the
same product for ≥ 4 weeks prior to screening and be encouraged to continue
throughout the duration of the study if medically feasible.

- Karnofsky performance score ≥ 70 on at least one occasion within 45 days prior to
study entry

- Confirmation of the availability of the stored pre-entry fasting plasma, serum, and
cell samples. The site had to confirm that these samples had entered into the
Laboratory Data Management System (LDMS).

Exclusion Criteria:

- Current or past malignancy (except non-melanoma cancer of the skin)

- Coronary artery disease (CAD) or CAD equivalent including diabetes mellitus or
National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)
calculated 10-year coronary heart disease (CHD) risk of > 20%.

- Known cirrhosis.

- Known chronic active hepatitis B or C.

- Thyroid-stimulating hormone (TSH) < 1.0 x lower limit of normal or > 1.0 x ULN.

- Known inflammatory conditions, such as, but not limited to, rheumatoid arthritis
(RA), systemic lupus erythematosus (SLE), sarcoidosis, inflammatory bowel disease
(IBD), chronic pancreatitis, autoimmune hepatitis, myositis, or myopathy.

- Pregnant or breast-feeding.

- Previous intolerance to any statin or any of its components.

- Use of any lipid-lowering therapies including all statin drugs, Omega 3 fatty
acids/fish oil, red yeast rice, and niacin products ≥ 1 g/day (e.g., niacin,
nicotinic acid, vitamin B3) taken within 45 days prior to study entry. More
information on this criterion can be found in the study protocol.

- Immunosuppressant use, such as, but not limited to, systemic or potentially systemic
glucocorticoids (including nasal or inhaled steroids), azathioprine, tacrolimus,
mycophenolate, sirolimus, rapamycin, or cyclosporine within 45 days prior to study
entry.

- Use of any systemic antineoplastic or immunomodulatory treatment, investigational
vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin
(IVIG) within 45 days prior to study entry. More information on this criterion can be
found in the study protocol.

- Concurrent use of prohibited medications. More information on this criterion can be
found in the study protocol.

- Heavy alcohol use as defined by the National Institute on Alcohol Abuse and
Alcoholism (NIAAA)
(http://pubs.niaaa.nih.gov/publications/Practitioner/pocketguide/pocket_guide3.htm)
and alcohol or drug use or dependence that, in the opinion of the site investigator,
would interfere with adherence to study requirements.

- Current use of anticoagulation therapy other than ≤ 325 mg of daily aspirin.

- Known coagulopathy, deep venous thrombosis, pulmonary embolism within 6 months prior
to study entry.

- Known active or recent (not fully resolved within 4 weeks prior to study entry)
bacterial, fungal, parasitic, or viral infections.

- Known history of recurrent rectal and/or genital herpes simplex virus (HSV) or
varicella zoster virus (VZV) infection within 12 weeks prior to study entry.

- Serious illness or trauma requiring systemic treatment and/or hospitalization within
4 weeks prior to study entry.

- History of stroke.