Dipeptidyl Peptidase-4 Inhibition and Immune Function in HIV

Inclusion Criteria: 1. Thirty 18-65 yr old HIV-infected men and women (with source documentation of HIV status) who are stable on any antiretroviral therapy (cART) regimen 2. Have stable (at least the past 12-months) immunologic (\>350 CD4+ T-cells/µL) and virologic (\<50 copies HIV RNA/mL) status. 3. BMI 18-42kg/m2; 4. Normal blood chemistry for at least 1 month prior to enrollment; 5. Platelet count \> 30,000/mm3, absolute neutrophil count \>750/mm3, transaminases \< 2.5x the upper limit of normal (ULN). 6. Long-term non-progressors (not on ART) are not eligible. Exclusion Criteria: 1. CD4+ T-cell count \<350 cells/µL or detectable plasma HIV RNA (\>50 copies HIV RNA/mL) within the past 12-months. During the study, if CD4+ T-cell count declines by \>100 cells/µL, or if plasma HIV RNA becomes detectable (\>50 copies HIV RNA/mL after repeat analysis 2wks apart), and the participant denies any lapse in their anti-HIV medication regimen, the study medication will be stopped and an adverse event documented. If at any time during the study, two participants experience a reduction in T-cell count \>100 cells/µL, or their plasma HIV RNA levels become detectable (\>50 copies HIV RNA/mL after repeat analysis 2wks apart), and they are confirmed (by unblinding) to have received sitagliptin, the study will be stopped for serious safety concerns. 2. Systemic, secondary or opportunistic infection within past 12-months. 3. Fasting glucose intolerance (FBG \>100mg/dL), fasting hyperinsulinemia (\>15µU/mL), or fasting insulin resistance (Homeostasis model for insulin resistance (HOMA) \>3.0). Any agents that might alter glucose metabolism (insulin, TZDs, metformin, glucocorticoids, sulfonylurea, corticosteroids, megace, rhGH, GH-secretagogue) during the 3 months prior to enrollment or at any time during enrollment. Volunteers with T2DM, IDDM or diabetic ketoacidosis will not be enrolled. 4. History of serious CV disease or NYHA Functional Class III or IV, (e.g., recent MI, unstable angina, edema, CHF, CAD, CABG, valve disease (murmur), stroke, uncontrolled high blood pressure (resting \>160/95 mmHg), irregular heart rhythm, resting ST-segment depression \>1mm). Treatment with medications for a CV condition (cardiac glycosides α- or ß-blockers). Some antihypertensive medications (calcium-channel blocker, diuretic, angiotensin II receptor blockers (ARB), angiotensin converting enzyme inhibitors (ACE)) will be permitted. 5. Moderate to severe renal insufficiency. Serum creatinine \>1.7 mg/dL (men) \>1.5 mg/dL (women). 6. Known allergy or hypersensitivity to DPPIV-inhibitors. 7. Plan to change anti-HIV medication regimen or prophylaxis for opportunistic infection within 6-months of starting study.Transitions among efavirenz-based regimens will be allowed (e.g., Efavirenz + lamivudine + zidovudine (combivir) to Efavirenz + emtricitabine + tenofovir (Atripla)). 8. Lipid-lowering medications are permitted (fibrate or statin or niacin), but must be stable on that agent for at least 3 months prior to enrollment. Lipid-lowering agents cannot be started during the treatment period. 9. Chronic hepatitis B infection (HB surface antigen positive). Active hepatitis C infection (detectable Hep C RNA). Those who have cleared hepatitis B or C infection are eligible. 10. Hematocrit \<34% in men or \<25% in women with symptoms (fatigue, "tired-legs", shortness of breath). Hemoglobin \<10 gm/100ml with symptoms. 11. Nausea, vomiting, diarrhea (\>4 loose stools/day) that are unresponsive to treatment. History of eating disorder or significant GI-disease. 12. Pregnant or nursing mothers. Women must agree to use an acceptable form of birth control during the study. If birth control pills are used, the woman must be stable on these medications for at least 6 months prior to enrollment. 13. Active malignancy or treatment with chemotherapeutic agents or radiation therapy (within past 12 months). 14. \>10% unintentional body weight loss during the 12 months prior to enrollment. 15. "Blinded" investigational drugs/medications during the 3 months prior to enrollment that will not be unblinded before enrollment. Open-label investigational drugs are permitted (within past 3 months, no plan to stop during enrollment and not known to affect glucose, lipid, adipose tissue or liver metabolism). 16. Over the counter agents that might alter glucose, lipid, or adipose tissue metabolism (e.g., creatine monohydrate, chromium picolinate, amino acid/protein supplements, medium- or long-chain fatty acids) within 1 month of enrollment. These supplements are not permitted during the treatment period. 17. Reduced cognitive function/unable to provide voluntary informed consent. Prisoners are excluded. 18. Active substance abuse that the physician-scientist believes may compromise safety, compliance, or interfere with study drug or data interpretation. 19. Any cytokine or anti-cytokine therapy during 3 months prior to enrollment.