Effectiveness of Sitagliptin for HIV Insulin Resistance and Inflammation

Inclusion Criteria:

• 18-65 yr old HIV infected men and women.

• Stable (at least the past 6 months) on combined antiretroviral therapy (cART).

• Stable immune (> 300 CD4+ T-cells/µL) and virologic (< 50 copies HIV RNA/mL) status.

• Insulin resistant/impaired glucose tolerance (fasting glucose 100-125mg/dL, or 2-hrglucose 140-200mg/dL or fasting HOMA-IR= 2.5-6.0).

• Waist circumference > 102 cm (men), > 88 cm (women).

• BMI > 20 kg/m2.

• Fasting hypertriglyceridemia > 150 mg/dL.

• Low HDL-cholesterol (< 40 mg/dL in men or < 50 mg/dL in women).

• Platelet count > 30,000/mm3.

• Absolute neutrophil count > 750/mm3.

• Transaminases < 2.5x the upper limit of normal.

• Long-term non-progressors (not taking anti-HIV medications) are not eligible.

Exclusion Criteria:

• Diabetes (T2DM, IDDM or diabetic ketoacidosis) or taking any glucose-loweringmedication (e.g., insulin, TZDs, metformin, sulfonylurea).

• Any agent that might artifactually alter glycemic control (e.g., glucocorticoids,megace, rhGH, GH-secretagogue, testosterone derivatives, creatine monohydrate,chromium picolinate, AA/protein supplements, medium- or long-chain fatty acids) during 6 months prior to or during enrollment.

• History of serious CV disease. NYHA Functional Class III or IV (e.g., recent MI,unstable angina, edema, CHF, CAD, CABG, stroke, resting hypertension > 160/95 mmHg),irregular heart rhythm, resting ST-segment depression > 1mm). Treatment withmedications for CV condition (e.g., α- or ß-blockers). Some BP-lowering medications (Ca++channel blocker, diuretic, or ACE inhibitor) are permitted.

• Moderate to severe renal insufficiency. Serum creatinine > 1.7 mg/dL (men) > 1.5 mg/dL (women).

• Plan or anticipate a change in anti-HIV medications during the study.

• Lipid-lowering medications are permitted (fibrate or statin or niacin), but must bestable on that agent for at least 6 months prior to enrollment. Lipid-lowering agentscannot be started during the treatment period.

• Chronic hepatitis B (HBV-surface antigen positive). Active hepatitis C (detectable HepC RNA).

• Positive urine drug test for opiates, methamphetamine, heroin, cocaine. Activesubstance abuse that the MD-scientist believes may compromise safety, compliance,interfere with study drug or data interpretation.

• Hematocrit < 34% in men or < 25% in women with symptoms (fatigue, "tired-legs",shortness of breath). Hemoglobin < 10 gm/dL with symptoms.

• Pregnant or nursing mothers. Women must agree to use an acceptable form of birthcontrol during the study. If using birth control pills-must be stable on thismedication for at least 6 months prior to enrollment.

• Active malignancy or treatment with chemotherapeutic agents or radiation therapy orany cytokine or anti-cytokine therapy during 6 months prior to enrollment.

• History of pancreatitis

• > 10% unintentional weight loss during the 6 months prior to enrollment.

• Reduced cognitive function/unable to provide voluntary informed consent. Prisoners areexcluded.

• Blinded investigational drugs for 3 months prior to enrollment that will not beunblinded before enrollment.

• Nausea, vomiting, diarrhea (> 4 loose stools/day) that are unresponsive to treatment.