Effects of Switching Efavirenz to Raltegravir on Vascular Function and Bone Markers in HIV-infected Patients
Condition: HIV
Intervention: Tenofovir/emtricitabine; Tenofovir/emtricitabine/efavirenz; Raltegravir
Intervention description: Efavirenz will be switched to raltegravir 400mg orally twice daily while continuing tenofovir/emtricitabine; Continued therapy with tenofovir/emtricitabine/efavirenz; Efavirenz will be switched to raltegravir 400mg orally twice daily while continuing tenofovir/emtricitabine
Intervention MeSH terms: Tenofovir; Emtricitabine; Efavirenz; Raltegravir Potassium
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Endothelial function; Vitamin D; Efavirenz; Raltegravir

Summary:

      Efavirenz, a commonly used HIV medication, may cause worsening vascular function and bone
      problems. The purpose of this study is to determine if switching efavirenz to raltegravir, a
      newer HIV medication, will improve vascular function and tests of bone health.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infection, documented by (1) any licensed rapid HIV test or HIV enzyme or
             chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and
             confirmed by a licensed Western blot or a second antibody test by a method other than
             the initial rapid HIV and/or E/CIA, or (2) by two detectable HIV-1 antigens, or (3)
             two detectable plasma HIV-1 RNA viral loads.

          -  Age equal to or greater than 18 years.

          -  Receipt of TDF/FTC/EFV as the subject's initial ART regimen for at least one year
             prior to Screening.

        Note: Interruptions in TDF/FTC/EFV of up to 10 days total during the 90 days prior to
        screening are allowed.

        Note: Subjects who had received 3TC (lamivudine) with TDF/EFV as part of their initial
        regimen but have received TDF/FTC/EFV for at least one year prior to screening will be
        eligible.

          -  HIV-1 RNA level <50copies/mL at screening and with a history of having an HIV-1 RNA
             level of <50copies/mL between 1 and 6 months prior to screening.

          -  At least one genotypic resistance test done prior to initiation of TDF/FTC/EFV
             suggesting no evidence of antiretroviral resistance to any nucleos(t)ide reverse
             transcriptase inhibitor or non-nucleoside reverse transcriptase inhibitor.

          -  No previous use of raltegravir or other integrase inhibitor.

          -  For women of reproductive potential, a negative urine pregnancy test at screening and
             willingness to use two forms of birth control during the course of the study.
             Acceptable forms of birth control include condoms (with or without a gel that can kill
             sperm), a diaphragm or cervical cap (with or without a gel that can kill sperm), an
             intrauterine device (IUD), or hormonal-based birth control ("the pill").

        Exclusion Criteria:

          -  Inability to complete written, informed consent.

          -  Incarceration at the time of any study visit.

          -  Diagnosed vascular disease (history of angina pectoris, coronary disease, peripheral
             vascular disease, cerebrovascular disease, aortic aneurysm, or otherwise known
             atherosclerotic disease).

          -  Diagnosed disease or process, besides HIV infection, associated with increased
             systemic inflammation (including, but not limited to, systemic lupus erythematosis,
             inflammatory bowel diseases, other collagen vascular diseases).

        Note: Hepatitis B or C co-infections are NOT exclusionary

          -  Known or suspected malignancy requiring systemic treatment within six months of
             screening.

          -  History of ADA-defined diabetes mellitus

        Note: History of gestational diabetes is not exclusionary if the potential subject does not
        have current ADA-defined diabetes.

          -  History of migraine headaches.

          -  History of Raynaud's phenomenon.

          -  History of cardiac arrhythmias or cardiomyopathy.

          -  Uncontrolled hyperthyroidism or hypothyroidism, defined as TSH values outside of the
             local reference range on most recent clinical assessment.

          -  History of hypoparathyroidism or hyperparathyroidism, even if treated.

          -  Known allergy or intolerance to nitroglycerin.

          -  History of carotid bruits.

          -  Creatinine clearance < 50mL/min (using the Cockcroft-Gault equation) using a serum
             creatinine level measured at screening.

          -  Hemoglobin < 9.0mg/dL at screening.

          -  Alanine aminotransferase (ALT) level or aspartate aminotransferase (AST) > 3 times ULN
             at screening.

          -  Total bilirubin > 2.5 times ULN at screening.

          -  Fever, defined as T ≥ 38.0C within 48 hours prior to screening.

        Note: Fever within 48 hours prior to each main study visit will require postponement of
        that study visit until the patient has defervesced (T < 38.0C) for at least 48 hours;
        fevers continuing past the allowed study visit timeframe will result in study
        discontinuation.

          -  Therapy for acute infection or other serious medical illnesses within 14 days prior to
             screening.

        Note: Therapy for acute infection or other serious medical illnesses that overlaps with a
        main study visit will result in postponement of that study visit until the course of
        therapy is completed; postponement outside of the allowed study visit timeframe will result
        in study discontinuation.

          -  Pregnancy or breastfeeding during the course of the study.

          -  Hypotension, defined as systolic blood pressure < 90mmHg, at time of screening.

        Note: Hypotension noted prior to brachial artery reactivity testing on each main study
        visit will result in study visit postponement of at least one day until systolic pressure
        is ≥ 90mmHg the morning of brachial reactivity testing; postponement outside of the allowed
        study visit timeframe will result in study discontinuation.

          -  Uncontrolled hypertension, defined as systolic blood pressure > 160mmHg or diastolic
             blood pressure > 100mgHg at screening.

          -  Receipt of investigational agents, cytotoxic chemotherapy, systemic glucocorticoids
             (of any dose), or anabolic steroids at screening.

        Note: Physiologic testosterone replacement therapy is not exclusionary.

          -  Receipt of lipid-lowering drugs or anticonvulsants (defined as those drugs with
             significant CYP 450 induction or inhibition) screening.

          -  Use of sildenafil, vardenafil, or tadalafil within 72 hours (before or after) of each
             main study visit.

          -  Active drug or alcohol use or dependence that, in the opinion of the investigator,
             would interfere with adherence to study requirements.