The Effect of Hyperbilirubinemia on CV Disease, Neurocog Function and Renal Function
The Effect of Hyperbilirubinemia on CV Disease, Neurocog Function and Renal Function
Use of some protease inhibitors is associated with elevations of a blood pigment called
 bilirubin. This may occasionally lead to yellowing of the eyes (scleral icterus) or jaundice,
 but in the general population bilirubin elevations have been shown to have antioxidant and
 anti-inflammatory properties that could be associated with reduced risk of cardiovascular or
 other disease events.

 Inflammation may also be relevant to neurocognitive impairment in HIV (Human Immunodeficiency
 Virus) infection hence elevations of bilirubin may also be protective against neurocognitive
 impairment.

 The purpose of this study is to evaluate the impact of hyperbilirubinemia (HBR) on risk of
 heart and renal diseases, and cognitive function.
Use of some protease inhibitors is associated with unconjugated hyperbilirubinemia as a
 result of inhibition of the UGT1A1 enzyme.

 Elevated levels of unconjugated bilirubin are best characterized among individuals with
 Gilbert syndrome, which is the most common inherited cause of unconjugated
 hyperbilirubinemia, present in 3-10% of the general population. Gilbert syndrome arises
 through variants in the UGT1A1 enzyme, thus these PIs induce a biochemical picture similar to
 Gilbert syndrome. Although elevations of bilirubin may occasionally lead to scleral icterus
 or jaundice, cohort studies of individuals with Gilbert syndrome indicate bilirubin
 elevations may have antioxidant and anti-inflammatory properties and are associated with
 reduced risk of cardiovascular events.

 Inflammation may also be relevant to cardiovascular (CV) risk, neurocognitive impairment and
 renal disease in HIV infection. This study seeks to investigate any association between
 antiretroviral associated HBR and CV risk markers, neurocognitive impairment and renal
 dysfunction
Inclusion Criteria:

 1. The ability to understand and sign a written informed consent form, prior to
 participation in any screening procedure and must be willing to comply with all study
 requirements.

 2. Documented HIV-1 infection.

 3. >18 years of age

 4. Stable on PI based therapy with TDF/FTC or ABC/3TC > 6 months with either normal
 bilirubin or bilirubin >2.5 X upper limit

 5. Stable for > 3 months on lipid lowering therapy, anticoagulant, hormone supplements,
 metformin (for lipohypertrophy) or other metabolic therapies

 6. No known or past history of cardiovascular disease, neurocognitive disorder or renal
 disease.

 Exclusion Criteria:

 1. Grade 1-2 Bilirubin

 2. Known CV disease (angina, coronary artery disease, peripheral vascular disease,
 stroke, congestive cardiac failure or myocardial dysfunction), Diabetes Mellitus,
 antihypertensive therapy

 3. Chronic NSAID use including low dose aspirin

 4. Known renal or CNS or neurocognitive disease

 5. HIV RNA >400copies/ml in last 6 months

 6. Change of antiretroviral Therapy in last 6 months

 7. Active Hepatitis B (sAg +ve) or hepatitis C (detectable HCV RNA,, treated or cleared
 Hepatitis C permitted if infection and/or treatment > 6months previous)

 8. Use of anabolic steroids. Cutaneous administered testosterone supplements stable for
 >3 months for documented hypogonadism permitted. Oral contraceptives stable for 3
 months permitted.