Cardiovascular Risk in HIV Patients on Antiretroviral Therapy Therapy: The MHEART Study
Condition: Cardiovascular Disease Risk in HIV Patients; Endothelial Function
MeSH terms: Cardiovascular Diseases
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      CVD accounts for 15% of all deaths in Malawi. Both HIV and ART are risk factors for CVD
      through direct toxic and inflammatory cardiovascular effects. (44,45). At the moment, one out
      of every 10 Malawian is HIV positive and roughly 8 out of 10 of those infected are now on ART
      (2). Therefore, HIV and ART may be contributing to the burden of CVD in Malawi. Currently,
      there are only a few studies assessing CVD risk in the HIV patient population on ART. In
      Malawi, no such studies exist. Therefore, the investigators propose a novel study assessing
      baseline cardiovascular disease risk using two novel ultrasound technologies in HIV patients
      on ART. Cardiovascular disease risk will be assessed using surrogate cardiovascular markers
      of disease. These surrogates include markers of endothelial function and cardiovascular
      modulating inflammatory biomarkers. The inflammatory biomarkers measured will be TNF-alpha,
      IL-6, and CRP. Aspirin, by way of its antiplatelet and anti-inflammatory effect has been
      demonstrated to inhibit atherosclerosis by way of decreasing TNF-alpha, IL-6, CRP and
      improving endothelial function. Therefore a second aim of the study will be to demonstrate
      that aspirin improves surrogate markers of atherosclerosis.
    

Detailed description: 
      To address our objectives we have designed a six-month prospective randomized controlled
      study (RCT) investigating cardiovascular disease risk in HIV patients on ART with the
      implementation of an aspirin versus placebo strategy to investigate whether this risk can be
      modified. As nearly all HIV patients are anticipated to be on ART in the upcoming decade, we
      have decided to open this study to only virally suppressed HIV on ART. A total of 100 virally
      suppressed HIV positive Malawians on ART will be enrolled in this study. Initial screening
      will occur in the patient population identified as being HIV positive with viral load
      suppression on ART in the last 3 months. The initial screening will provide cross-sectional
      information on baseline demographic, clinical, and laboratory characteristics of virally
      suppressed HIV patients on ART and will assess baseline cardiovascular risk using laboratory
      biomarker data and endothelial function as surrogate markers (see section under procedures).
      Ability of distal arteries to dilate under stress will be measured using novel ultrasound
      technologies applicable to the limited resource healthcare settings in Malawi. After initial
      screening, eligibility into the study will be determined and selected participants will be
      randomized into one of two arms:

        1. Oral aspirin 325mg daily

        2. Oral placebo daily.

      This longitudinal RCT will reassess cardiovascular risk at the one-month, 3-month, and
      six-month mark using the same CVD surrogate measurements of atherosclerosis performed during
      the initial screening.

      Procedures assessing surrogate CVD markers for atherosclerosis:

        1. Laboratory analysis (Venipuncture): Inflammatory biomarkers

           • C-Reactive Protein (CRP), Interleukin-6, Tumor Necrosis Factor- alpha

        2. Endo-PAT analysis

        3. Brachial Flow Mediated dilation

        4. Carotid Intima-Media Thickness
    

Intervention name(s): Aspirin; Placebo
Intervention type(s): Drug; Drug
Intervention MeSH terms: Aspirin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention