The blood vessels that carry blood from the heart to the rest of the body are normally capable of relaxing and constricting when needed to provide more or less blood to the body. The inability of blood vessels to relax and widen may increase the risk of heart disease and stroke. One potential cause of this inability is inflammation. Because HIV infection is associated with inflammation, it is possible that the blood vessels in people infected with HIV may not relax properly. The purpose of this study is to determine whether people infected with HIV have worse blood vessel function than people without HIV infection.

Normally the insides of blood vessels either widen or narrow in response to the need for more or less blood flow. This is a function of the endothelial cells, which are the cells that line the inner layer of blood vessels. However, in some people endothelial function is impaired, which may put them at an increased risk of heart disease and stroke. It is widely assumed that HIV-infected people not yet receiving antiretroviral medications experience more impaired endothelial function than HIV-uninfected people, possibly because of the link between HIV and inflammation. However, no rigorously controlled study has yet to be performed to verify this presumption. It is important to establish whether HIV infection itself, and not the use of antiretroviral medications, is indeed the cause of impaired endothelial function. This study will compare endothelial function in people with HIV who are not already receiving antiretroviral medications and in people without HIV. Specifically, inflammation, immune activation, endothelial activation, and metabolic measures will be compared.

This study will involve two groups of participants. The first group will consist of people with HIV who are enrolling in two other separate HIV studies (NCT00864916 and NCT00796822), one lasting 8 weeks and the other lasting 48 weeks. The second group will consist of people without HIV who are similar to the first group in terms of age, sex, smoking status, and height. All HIV-infected participants will undergo assessments during the study visits of whichever other HIV study they are enrolled in. All HIV-uninfected participants will attend a main study visit that will include the following: a review of medical records and family medical history; measurements of blood pressure, heart rate, weight, temperature, and waist and hip circumferences; blood and urine collection; and a procedure called brachial artery reactivity testing, which is a noninvasive way to measure endothelial function. Some of the HIV-uninfected participants will continue in the study so that any changes in their endothelial function can be assessed. They will attend either two additional study visits at Weeks 4 and 8, which will correspond with one of the HIV studies, or three additional study visits at Weeks 8, 24, and 48, which will correspond with the other HIV study. The additional visits will include repeat testing except for blood and urine collection.

Inclusion Criteria for HIV-Infected Group:

• Positive HIV enzyme-linked immunosorbent assay (ELISA) test with confirmatory Western Blot
• Not currently receiving antiretroviral therapy

Inclusion Criteria for HIV-Uninfected Group:

• Negative HIV ELISA test at screening
• Within 10 years of age of the matched HIV-infected participant
• Same sex and current smoking status as the matched HIV-infected participant
• Height within 4 inches of the matched HIV-infected participant

Exclusion Criteria for All Participants:

• Inability to complete written informed consent
• Incarceration at the time of screening or main study visit
• Diagnosed vascular disease (e.g., history of angina pectoris, coronary disease, peripheral vascular disease, cerebrovascular disease, aortic aneurysm, or otherwise known atherosclerotic disease)
• Diagnosed disease or process associated with increased systemic inflammation (e.g., systemic lupus erythematosis, inflammatory bowel diseases, or other collagen vascular diseases); Note: Hepatitis B or C co-infections are not exclusionary
• History of bleeding diathesis, gastrointestinal ulceration or bleeding, cerebrovascular aneurysm or bleeding, or retinal hemorrhage
• Known or suspected cancer requiring systemic treatment within 6 months of screening
• History of diabetes mellitus, as defined by the American Diabetes Association; Note: History of gestational diabetes is not exclusionary
• History of migraine headaches
• History of Raynaud's phenomenon
• History of cardiac arrhythmias or cardiomyopathy
• History of hypothyroidism or hyperthyroidism, even if treated; Note: Use of caffeinated products, except on the mornings of the study visits, is not exclusionary
• Known allergy or intolerance to nitroglycerin
• History of carotid bruits
• Creatinine clearance less than 50mL/min, using a serum creatinine level measured at screening
• Hemoglobin level greater than 9.0g/dL at screening
• Alanine aminotransferase (ALT) level or aspartate aminotransferase (AST) greater than three times the upper limit of normal (ULN) at screening
• Total bilirubin greater than 2.5 times ULN at screening
• Fever, defined as a temperature greater than 38.0 C within 48 hours prior to screening
• Received therapy for acute infection or other serious medical illness within 14 days prior to screening
• Pregnant or breastfeeding during the course of the study
• Hypotension, defined as systolic blood pressure less than 90mm Hg, at screening.
• Uncontrolled hypertension
• Receipt of anti-inflammatory agents (e.g., plaquenil, infliximab, etanercept, mycophenolate mofetil, sirolimus, tacrolimus, cyclosporine, pentoxifylline, thalidomide)
• Receipt of investigational agents, cytotoxic chemotherapy, systemic or topical glucocorticoids (of any dose), or anabolic steroids within 28 days of screening; Note: Physiologic testosterone replacement therapy is not exclusionary
• Receipt of lipid-lowering drugs, aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs), acetazolamide, anticoagulants, anticonvulsants, or thyroid replacements within 7 days prior to screening
• Use of sildenafil, vardenafil, or tadalafil within 72 hours (before or after) of each main study visit
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements

HIV-infected people will be recruited from infectious diseases outpatient clinics of Wishard Hospital and Indiana University Hospital. They will be enrolled in one of two other HIV trials. HIV-uninfected people will be recruited from the Indianapolis general population.