Effect of HAART Vs. Statin Treatment on Endothelial Function and Inflammation/Coagulation

Inclusion Criteria

• •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 PSWP.
• •No ART within the past 30 days.
• •Ability and willingness of participant or legal guardian/representative to provide informed consent.
• •In the opinion of the investigator, no medical, mental health or other condition that precludes participation.
• •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 protocol.
• •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 feasible.
• •* 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.