Soy Modulation of Immune Activation, LDL- Levels, and Lowering Inflammation by Pretzel Isoflavone Dietary Intervention

• Females and males aged 18 years or older.
• ACC/AHA 2013 Guidelines 10 year risk between \<15%
• HIV-1 infection as documented by any licensed ELISA (enzyme-linked immunosorbent assay) test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 ribonucleic acid (RNA), or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
• Receiving any stable Department of Health and Human Services (DHHS) recommended or alternative antiretroviral regimen for at least the last 12 weeks prior to study entry.
• Cumulative duration of antiretrovirals for at least 12 months at study entry.
• Documentation of at least 2 consecutive HIV-1 RNA levels of ≤50 copies/mL using any standard commercially assay for at least 6 months prior to study entry. An isolated (non-consecutive) HIV RNA > 50 copies/mL (but less than 400 copies/mL) within the previous 12 months is permitted.
• Provides written informed consent and is capable of reading and comprehending the informed consent.
• Meet Karnofsky performance status ≥70.
• Have a body mass index (BMI) between 20-35 kg/m2.
• Have a fasting total cholesterol levels of ≥200mg/dL AND either LDL cholesterol level of 120 to 190mg/dL or a HDL ≤ 40 mg/dL

• Laboratory values obtained at screening:

  • ANC (absolute neutrophil count) >1000/mm3
  • Hemoglobin >11 g/dL
  • Platelets ≥100,000/mm3
  • Calculated creatinine clearance (CrCl) >60 mL/min, as estimated by the Cockcroft-Gault equation
  • ALT (alanine aminotransferase) \<5 x ULN (upper limit of normal) or ALT \<3 x ULN and total bilirubin \<1.5 x ULN Note: If the potential subject is taking an atazanavir-containing regimen at the time of screening, total bilirubin ≤5 x ULN is acceptable.
  • Hgb A1c (Hemoglobin A1c) ≤6.5%
• Have no plans to alter antiretroviral therapy (including structured treatment interruptions), diet (beyond soy intervention) or exercise regimens during the course of the study.
• Agree to collect urine for 24 hours and have blood collected, at specified time points.
• Agree to abstain from use of herbal or dietary supplements during the 6 weeks for the short-term study or 28 weeks for the placebo-controlled study or any other supplements that might interact with dietary soy intervention.
• Agree to follow a daily vitamin and mineral supplement regimen for 6 weeks for the short-term study or 28 weeks for the placebo-controlled study.
• Agree to abstain from legume foods or products made from these ingredients which are known to be high in isoflavones for 6 weeks or 28 weeks:

Soy: Edamame, Miso, Soy cheese, Tofu, Tempeh, Protein bars, Soymilk, Natto, Soy meat substitutes Beans: Navy, Kidney, Green beans, Lima, Pinto, Black beans, Cannellini, and Chickpeas Peas: Green, Snow, Black-eyed Peanuts: Peanuts, Peanut butter (1 tablespoon/week permitted) Sprouts: Alfalfa, Clover, Mung bean, Soybean

Exclusion Criteria:

• Need (or anticipated need in the next 24 weeks) for lipid modification pharmacotherapy or hypolipidemics (e.g., statins or fibrates) or hypoglycemic therapy.
• A clinically important illness within 14 days prior to study entry not explicitly excluded by the protocol, a physical or psychiatric disability, or a laboratory abnormality that might place the subject at increased risk by being exposed to the medications in this study or which might confound the interpretation of this investigation.
• Chronic hepatitis B or C infection Note: Participants who have been treated for their hepatitis C and have achieved a sustained virologic response (SVR) of 12 may participate.
• Any active or chronic uncontrolled inflammatory condition.
• Diarrhea or vomiting of Grade ≥ 2 within 14 days prior to study entry.
• An active AIDS-defining opportunistic infection or disease (for the purpose of this study, a cluster of differentiation 4 (CD4) count \<200 cells/mm3 in the absence of any other AIDS-defining indicator condition is not considered an AIDS-defining event).
• Inability to maintain adherence to study schedule or communicate with study personnel.
• Current alcohol or recreational drug use which in the investigator's opinion interferes with the subject's ability to comply with dosing schedule and protocol evaluations.
• Any change in the last 24 weeks in therapy with prescription omega-3 fatty acids (>2 gram/day of Lovaza®), fibrates, or prescription niacin. Therapy with OTC (over the counter) omega 3 fatty acids or with ≤ 2 g Lovaza® is allowed. Any statin therapy for longer than 14 days received in the last 24 weeks is exclusionary.
• Have had a full treatment course/regimen of antibiotics 6 months prior to start of study.
• Known sensitivity or allergy or intolerance to wheat, soy, or any of the ingredients found in pretzels (yeast, soy bean oil, palm oil, or diastase enzymes).
• Have had a malignancy of any kind or ongoing chemotherapy, radiation therapy, or other cancer-related treatment.
• Concurrent use of immunosuppressant medications, including but not limited to immunomodulating agents, steroids, and chronic anti-inflammatory agents.
• Active metabolic or digestive illness including malabsorptive disorders, diabetes mellitus (indicated by Hgb A1c of ≥6.8% or on exogenous insulin therapy), renal insufficiency, hepatic insufficiency, hyper- or hypothyroidism, or short bowel syndrome, have an active or a recent history of any condition that causes altered immunity, co-morbid cardiac, pulmonary, renal, neurologic, and endocrine.
• Known underlying myositis or muscle disease.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, hypertension, or psychiatric illness/social situation that would limit compliance with study requirements.
• Lack of regular access to a household freezer (for pretzel storage).