A Randomized Controlled Trial to Compare the Effects of Highly Active Antiretroviral Therapy (HAART) Versus Statin Therapy on Endothelial Function and Markers of Inflammation/Coagulation In HIV-Infected Individuals With High CD4 Cell Counts
- HIV-1 infection
- Willingness to defer initiation of ART for up to 24 weeks or statin therapy for up to
12 weeks after study entry.
- CD4+ cell count >500/mm3 within 60 days prior to study entry obtained at any
laboratory that has a CLIA certification or its equivalent.
- No prior ART of more than 10 cumulative days with the following exceptions:
- Use of ART drugs as part of post-exposure prophylaxis (PEP) provided the
participant did not acquire HIV-1 infection from the event that required PEP.
- ART use during pregnancy that resulted in virologic suppression based on the
assay available at the time and was not complicated while on therapy either by
detectable HIV-1 RNA following suppression or the development of resistance.
Women who received ZDV monotherapy prior to the availability of viral load
testing will still be considered eligible as long as ZDV was not taken for more
than 12 weeks. ART must have been stopped within 4 weeks of delivery and cannot
have been received within 6 months of the A5292 screening visit.
- Receipt of ARV drugs while HIV-uninfected, with documentation of negative HIV-1
serology at least 90 days after completion of ARV drugs.
- 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), in addition to those listed on the A5292
- No ART within the past 30 days.
- Ability and willingness of participant or legal guardian/representative to provide
- In the opinion of the investigator, no medical, mental health or other condition that
- Certain laboratory values obtained within 60 days prior to entry, as indicated in
section 4.1.10 of the protocol.
- Framingham Risk Score (FRS) greater than/equal to 10% OR FRS greater than/equal to 6%
if hsCRP > 3.0 mg/L OR participant has controlled type ll diabetes mellitus.
- No evidence of any exclusionary resistance mutations based on results from any
genotype assay from any laboratory that has a CLIA certification or its equivalent.
The result must either be available from previous testing or must be obtained prior
to entry and have been reviewed by the site investigator. If a genotype is submitted,
but for technical reasons cannot be completed, the participant will still be allowed
to enroll, if otherwise eligible. (The protocol will not provide the resistance
assay). An exclusionary resistance mutation is defined in section 4.1.12 of the
- Completion of the pre-entry FMD assessment.
- For women of reproductive potential, negative serum or urine pregnancy test with a
sensitivity of ≤ 25 mIU/mL at screening and within 72 hours prior to study entry.
- Female study volunteers of reproductive potential include women who have not been
post-menopausal for at least 24 consecutive months, (i.e., who have had menses within
the preceding 24 months, or women who have not undergone surgical sterilization,
specifically hysterectomy and/or bilateral oophorectomy).
- Contraception requirements-
- All subjects must agree not to participate in the conception process and if
participating in sexual activity that could lead to pregnancy, must agree to use
at least two reliable methods of contraception for 2 weeks before study
treatment, while receiving study treatment, and for 6 weeks after receiving
study treatment. As hormone-based contraceptives can affect coagulopathy
biomarkers, subjects who plan on using such a contraceptive during the study
must be taking the same product for at least 30 days prior to screening and be
encouraged to continue throughout the duration of the study, if medically
- Subjects receiving an EFV-based regimen must use a barrier method as one of the
two forms of contraception. Acceptable types of contraception include male or
female condoms (with or without a spermicidal agent), diaphragm or cervical cap
with spermicide, intrauterine device (IUD), and hormone-based contraceptive
- Female subjects who are not of reproductive potential or whose male partner(s) has
azoospermia are eligible to start study drugs without requiring the use of
contraceptives. Confirmation of the lack of reproductive potential is REQUIRED and
written documentation or oral communication from a clinician or clinician's staff
must be documented in source documents of either a physician report/letter, operative
report or other source documentation in the patient record, discharge summary,
laboratory report of azoospermia, or FSH measurement elevated into the menopausal
range as established by the reporting laboratory.
- Ability and willingness to complete the neuropsychological tests.
- Pregnancy or breast-feeding.
- Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or
- Known and documented cardiovascular disease (history of MI, coronary artery bypass
graft surgery, percutaneous coronary intervention, stroke, transient ischemic attack,
peripheral arterial disease with ABI <0.9 or claudication).
- Uncontrolled type II diabetes mellitus.
- History of hepatic cirrhosis.
- Known chronic inflammatory conditions such as, but not limited to, rheumatoid
arthritis, systemic lupus erythematosus, sarcoidosis, inflammatory bowel disease
(i.e., Crohn's disease or ulcerative colitis), chronic pancreatitis, or autoimmune
hepatitis, myositis, or myopathy.
- Known active or recent (not fully resolved within 30 days prior to study entry)
systemic bacterial, fungal, parasitic, or viral infections.
- Serious illness or trauma requiring systemic treatment and/or hospitalization within
4 weeks prior to study entry.
- Febrile (temperature >100.4 F [38 C]) or acute illness on the day the initial study
FMD is performed.
- Current severe congestive heart failure (New York Heart Association [NYHA] Class III
or IV). See A5292 MOPS for stages of heart failure.
- Uncontrolled hypertension within 60 days prior to study entry (systolic > 160 mm Hg
or diastolic > 100 mm Hg) from an average of two or more readings on two or more
occasions. NOTE: If the initial blood pressure reading is >160 mm Hg (systolic) or >
100 mm Hg (diastolic), then the participant must come back to the clinic for
additional readings prior to study entry.
- Documented untreated hypothyroidism per participant's medical records. Subjects with
treated hypothyroidism are allowed. NOTE: A thyroid stimulating hormone evaluation is
not required by this study.
- Current use of thyroid hormone supplements (e.g., levothyroxine, liothyronine,
thyroid extract) other than for treatment of hypothyroidism.
- Active cancer requiring systemic chemotherapy or radiation.
- Active brain infection, brain neoplasm, or space-occupying brain lesion requiring
acute, or chronic therapy. Subjects with active fungal meningitis, toxoplasmosis, or
CNS lymphoma are excluded from participation.
- Not fasting (see Section 6.3.1 of the protocol) or refraining from smoking or
exercising for the 8 hours prior to evaluations on the day of pre-entry FMD
assessment. Refer to A5292 MOPS for complete instructions.
- At the time of study entry planning to start or stop smoking during the first 12
weeks of the trial.
- At the time of study entry planning to initiate chronic therapy with
anti-inflammatory agents (such as aspirin) or immunomodulators during the first 12
weeks of the trial.
- At the time of study entry planning to significantly change diet or exercise habits
during the study period.
- Active drug or alcohol use or dependence that, in the opinion of the site
investigator, would interfere with adherence to study requirements.
- Any active psychiatric illness including schizophrenia, severe depression, or severe
bipolar affective disorder that, in the opinion of the investigator, could confound
the analysis of the neurological examination or neuropsychological test results.
- Hormonal anabolic therapies within 90 days prior to study entry including, but not
limited to growth hormone (Serostim), nandrolone (Deca-Durabolin), oxandrolone
(Oxandrin), oxymetholone (Anadrol-50), stanozolol (Winstrol), methyltestosterone
(Oreton Methyl), fluoxymesterone (Halotestin), megestrol acetate (Megace) and
- Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine,
systemic cytotoxic chemotherapy, or investigational immunomodulator therapy within 60
days prior to study entry. NOTE: Routine standard of care vaccinations including
hepatitis A and/or B, influenza, pneumococcal, and tetanus are permitted if
administered at least 7 days before entry evaluations.
- Current use of vitamin E supplements greater than 200 IU/day.
- Current use of vitamin C supplements greater than 250 mg/day.
- Any systemic glucocorticoid above replacement levels, defined as the equivalent of >
7.5 mg of prednisone daily, within 60 days of entry. NOTE: Topical, nasal and
inhaled glucocorticoid agents are permitted, provided the participant has been on
stable dosage(s) for at least 30 days prior to entry and has no plans to alter
dosage(s) and/or frequency during the first 12 weeks of the trial.
- Currently taking or anticipation of starting medication during the study for
hepatitis C including interferon and ribavirin.
- Use of investigational therapies within 90 days prior to study entry unless approved
by A5292 core team.