Cross-sectional and prospective studies are proposed to test the prediction that a higher proportion of HIV+ individuals with hazardous alcohol drinking with subclinical fasting dysglycemia will present with impaired oral glucose tolerance and dysfunctional metabolic skeletal muscle phenotype. Prospective studies will test the efficacy of an exercise intervention in improving glycemic control. Results will inform larger scale interventions to ameliorate metabolic comorbidities, improve health, quality of life, and possibly decrease hazardous alcohol drinking.

Brief Title

Alcohol & Metabolic Comorbidities in PLWHA: Evidence Driven Interventions

Official Title

Alcohol & Metabolic Comorbidities in PLWHA: Evidence Driven Interventions

Brief Summary

Cross-sectional and prospective studies are proposed to test the prediction that a higher <br /> proportion of HIV+ individuals with hazardous alcohol drinking with subclinical fasting <br /> dysglycemia will present with impaired oral glucose tolerance and dysfunctional metabolic <br /> skeletal muscle phenotype. Prospective studies will test the efficacy of an exercise <br /> intervention in improving glycemic control. Results will inform larger scale interventions to <br /> ameliorate metabolic comorbidities, improve health, quality of life, and possibly decrease <br /> hazardous alcohol drinking.

Detailed Description

Adult male and female in care PLWHA with fasting plasma glucose (FPG) >94 mg/dL and <125
mg/dL will be recruited. Measures of FPG and HbA1c obtained from overnight fasted subjects.
Alcohol use disorder (AUD) will be assessed by AUDIT and time-line follow back
questionnaires, coupled with Phosphatidylethanol (PEth) measures. Glucose tolerance will be
assessed by oral glucose tolerance test (OGTT). Blood sample collected at the time of the
OGTT will be used for determination of circulating levels of adipokines (adiponectin and
resistin).

A subset of adult male and female PLWHA +/- AUD with impaired OGTT will be recruited to
undergo skeletal muscle (SKM) biopsy (vastus lateralis), 90 min after a defined (calorie and
nutrient composition) meal (i.e.,Ensure, Carnation Instant Breakfast). Muscle samples will be
used for phenotype characterization (markers of inflammation, insulin signaling,
mitochondrial homeostasis) and for myoblast isolation.

Adult male and female PLWHA +/- AUD with impaired OGTT will undergo a moderate intensity
aerobic exercise intervention that will include the wearing of an accelerometer (i.e. Fitbit
Zip) to monitor daily activity and steps. A SKM biopsy will be performed after completion of
the exercise protocol in a subset of subjects to examine the changes in gene expression and
myoblast mitochondrial oxidative capacity. We will expand recruitment by enrolling PLWHA +/-
AUD based on a FPG between 94-120 mg/dL to participate in the exercise intervention.
Clearance for participation in this study will require EKG, completion of a physical activity
readiness questionnaire, and medical clearance from a staff clinician. Individuals with
significant peripheral neuropathies or the prevalence of significant cardiovascular
impairments (i.e. resting cardiac abnormalities or arrhythmias, severe hypertension, etc.)
will be excluded from exercise testing or intervention. The 10-week exercise intervention
program will consist of aerobic exercise 3 days per week of moderate intensity for 30-45
minutes each session with the goal of achieving 135 minutes per week. The program will begin
at low-moderate intensity (40 to 50% of heart rate reserve; HRR) and progress to a higher
intensity (50 to 60% HRR) exercise after week 4 of the program. The frequency and duration of
exercise sessions will remain constant after week 4 so the absolute dose of exercise will be
altered through increasing intensity, i.e. from low-moderate to more vigorous. All exercise
will be completed on a treadmill at the Louisiana State University Health Sciences Center
(LSUHSC) Wellness Center. Additionally, each participant will be provided with a Fitbit Zip
to monitor daily activity and steps. Data from the Fitbit Zip will be downloaded weekly
basis. Participants will be given a healthy step goal of 7000 steps per day. Based on initial
step counts after the first week of wearing the accelerometer, individual goals will be
discussed with the participants. Personal limitations that develop during the study period
(i.e. peripheral neuropathy, orthopedic limitation, etc.) will be monitored and will be
reason for exclusion from the exercise program. All sessions will be supervised and adherence
to the exercise prescription will be fully monitored under the supervision and care of Dr.
Stefany Primeaux in consultation with Dr. Neil Johannsen.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.