Exercise and Pioglitazone for HIV-Metabolic Syndromes

Inclusion Criteria

• 18-65 yr old HIV-infected men (n=40) and women (n=40).
• Source documentation of HIV status.
• Stable on highly active antiretroviral therapy (HAART) that may or may not include HIV-protease inhibitors for at least 3 months prior to enrollment. As of Jan 2005, HIV-infected long-term non-progressors will be included, even though they are not receiving HAART because it is likely that their disease status will not advance during the study period.
• Impaired glucose tolerance (IGT) or type 2 diabetes and fat redistribution. IGT is defined as: fasting (8hr) plasma glucose 100-126mg/dL or plasma glucose >140 mg/dL 2-hours after a 75g-oral glucose load. This definition (proposed/revised May 2006) includes volunteers with adult onset type 2 diabetes (non-insulin dependent diabetes), because we believe that these volunteers may benefit from the potential glucose-lowering actions of pioglitazone with or without exercise training. Fat redistribution is defined as any 2 of the following: waist-to-hip ratio >0.85 women or >0.95 men, or trunk/appendicular adipose ratio using whole-body DEXA >0.85 women or >1.3 men, or 120 cm2 women or >140 cm2 men, or a VAT/TAT ratio >0.30 women or >0.40 men. Overall, the eligibility criteria are designed to include subjects with metabolic syndromes that increase CVD risk, and the potential to gain the greatest benefit from pioglitazone and exercise training. These inclusion criteria will help select/maintain homogeneous groups of study participants.
• Plasma HIV RNA (Roche Amplicor® assay) 100 cells/µL and stable for previous 3 months.
• BMI 20-40kg/m2.
• "Normal" blood chemistries for at least 1 month prior to enrollment; platelet count >30,000/mm3, absolute neutrophil count 12µIU/mL, morning cortisol >22µg/dL, IGF-1 140/90 mmHg on 3 occasions), irregular heart rhythm, bundle-branch block, aortic stenosis, resting ST-segment depression >1mm) that would preclude exercise testing/training, or substantially increase risk of a CV-event during exercise, or would limit the subjects ability to participate in exercise training. Treatment with medications for a cardiovascular condition (cardiac glycosides, alpha- or beta-blockers). Some antihypertensive medications (Ca++-channel blocker, diuretic, or ACE inhibitor) will be permitted.
• Insulin-dependent diabetes mellitus (IDDM) or a history of ketoacidosis, symptomatic diabetic neuropathy or retinopathy, or renal disease (creatinine >3x ULN).
• Hematocrit 4 loose stools/day) that are unresponsive to treatment during 2wks prior to enrollment or that persists for >2wks during enrollment.
• Active secondary infection. Any significant change in chronic suppressive therapy for an opportunistic infection during the 1-month prior to enrollment.
• During the 3 months prior to enrollment, regular aerobic or weight lifting exercise training that exceeds the minimum (45min/d, 3d/wk, >75% exercise capacity) required for the metabolic, biochemical, and anthropomorphic benefits of exercise to be attained as described in the American College of Sports Medicine Guidelines. In Apr 2006, this exclusion criterion was modified in order to facilitate enrollment of volunteers who are moderately-highly active during the 3months prior to screening for this study. We will randomize volunteers who exercise regularly into the two treatment groups. This will reduce the potential confounding effects of regular exercise on the metabolic, biochemical, and anthropomorphic benefits of exercise training that is prescribed during the treatment phase. We have excluded several volunteers who are regular exercisers, and we believe we may be unnecessarily excluding them. They can be included, enrollment will be facilitated, and the study design will not be adversely affected, as long as we randomize them into pioglitazone or exercise+pioglitazone (1:1).
• Unwilling or unable to do supervised exercise 3 sessions/wk at the Medical School exercise facility. Any condit