2-5 Intermittent Caloric Restriction for Weight Loss and Insulin Resistance in HIV-Infected Adults With Features of the Metabolic Syndrome

The high prevalence of obesity coupled with chronic inflammation and immune activation places
human immunodeficiency virus (HIV)-infected individuals at increased risk for metabolic
complications emphasizing the need for more aggressive management of obesity and related
co-morbidities in the aging HIV-infected population. The most effective treatment for obesity
and metabolic syndrome is lifestyle modification, usually with a combination of caloric
restriction and increased exercise. Intermittent caloric restriction (ICR) or intermittent
fasting simplifies caloric restriction by severely limiting calories only a few days per week
and allowing ad lib diet on the other days. Weight loss benefits are similar to those seen
with conventional diets, however, data suggests possible added health benefits from
intermittent fasting.

We propose to study the benefits of a 2-5 intermittent caloric restriction (ICR) strategy on
weight, insulin resistance, and cardiovascular disease markers in obese HIV-infected adults
with features of the metabolic syndrome. In a prospective pilot study, 50 HIVinfected adults
will be randomized 1:1 to ICR or standard of care instruction of healthy diet and lifestyle
for a 12-week intervention period. We hypothesize that ICR (2 days per week) will be an
effective and acceptable diet strategy that will result in significant weight reduction,
improvements in insulin sensitivity and related metabolic parameters.

-INCLUSION CRITERIA:

1. Age 18 - 65 years

2. HIV RNA level less than or equal to 200 copies/mL for greater than or equal to1 year
(1 measure greater than or equal to 200 allowed if also <500 and preceded and followed
by one or more undetectable values)

3. CD4 > 200 cells/mL and no active opportunistic infection or malignancy

4. BMI greater than or equal to 30 kg/m^2

5. One or more components of the metabolic syndrome as defined below.

- Risk Factor: Waist circumference

- Men: Defining Level: > 102 cm

- Women: Defining Level: > 88 cm

- Risk Factor: Triglycerides, greater than or equal to 150 mg/dL

- Risk Factor: High density lipoprotein (HDL) cholesterol

- Men: Defining Level: < 40 mg/dL

- Women: Defining Level: < 50 mg/dL

- Risk Factor: Blood pressure, greater than or equal to 130 / greater than or equal
to 85 mmHg

- Risk Factor: Fasting glucose, greater than or equal to 110 mg/dL

6. Fasting blood glucose > 60 mg/dL at screening

7. Willingness to allow sample storage for future research

EXCLUSION CRITERIA:

1. Established diagnosis of diabetes mellitus use of anti-diabetes medications, or a
HgbA1C of >7.0 %

2. History of eating disorder, uncontrolled mood or thought disorder, significant
gastrointestinal disorder or malabsorption, or significant hepatic or renal impairment

3. Current use of medical therapy for overweight/obesity including phentermine, orlistat,
lorcaserin, naltrexone/bupropion, and liraglutide or history of weight loss surgery.
Concomitant use of medications with side effects known to potentially influence
appetite are allowed if on a stable dose for at least 12 months

4. History of symptomatic hypoglycemia.

5. Use of systemic glucocorticoids (stable dose daily inhaled corticosteroid allowed)

6. Chronic viral hepatitis C; subjects with a history of hepatitis C successfully treated
can enroll >12 months after sustained virologic response

7. Alcohol or substance use disorder in the past year as defined by DSM-V or positive
urine drug screen

8. Current pregnancy, actively seeking to become pregnant or breastfeeding

9. Any serious health or other condition which, in the opinion of the Principal
Investigator or their designee, could potentially interfere with the ability of a
subject to comply with the procedures and assessments of the protocol or to safely
participate and complete the study