PET Imaging and Lymph Node Assessment of IRIS in Persons With AIDS
Background: \- Sometimes people with HIV, the virus that causes AIDS, can have new or worsening symptoms soon after starting HIV medications. Often these symptoms are caused by immune reconstitution inflammatory syndrome (IRIS). Researchers want to study why and how people develop IRIS and how best to prevent and treat it.
Objectives: \- To learn the causes and effects of IRIS,and how to best manage it.
Eligibility: \- Adults 18 and older with HIV and low CD4 counts,, about to start HIV medicines; or those already taking HIV medicines with symptoms thought to be related to IRIS.
Design: * Participants not on ART will have screening blood tests for CD4 count, HIV viral load and genetic testing. * After the screening blood tests and before starting HIV medicines., participants will return for more than 1 visit for the following: * review of medical history\<TAB\> * physical and eye exams * blood, urine, and tuberculosis (TB) tests * electrocardiogram (EKG) * chest x-ray * apheresis: a blood drawing procedure where blood is removed from a vein, white blood cells are separated and collected, and the rest of the blood is returned to the person using another vein * \- PET scan - a procedure where a small amount of radioactive material is injected in a vein. The participant then lies on a table that slides into a scanner which takes images of the body. * lymph node biopsy * stool collection by swab * After completion of the above, HIV medicines will be started. * Follow-up visits will be at 2, 4, 8, and 12 weeks after starting ART, then every 12 weeks. Some of the tests above may be repeated. * Participants already on HIV medicines who may have IRIS will be screened over a 4 week time period to see if they really are experiencing IRIS. The screening process will include all of the items listed above. Follow-up visits will be at Weeks, 4, 8, 12 and then every 12 weeks. * The study will last 1 year for both groups but may be extended to 2 years (3 additional appointments) for some participants.
• Documentation of HIV-1 infection. Results from outside facilities will be accepted for enrollment.
• No recent (within the past two years) treatment with combination anti-retroviral therapy (ART). Patients with limited (no more than 2-3 weeks) recent use of potent combination ART may be eligible for study participation if, the opinion of the investigator, the ART usage will not impact the scientific validity of the protocol
• Documented CD4+ cell count less than or equal to 100 cells/mm(3) within the past 8 weeks.
• Residence within the wider Washington D.C. area (within a 100-mile radius from the NIH Bethesda campus) and plans to stay in the area for 48 weeks
• Men or women age greater than or equal to 18 years.
• Ability and willingness of subject (or legal guardian/representative) to understand study requirements and give informed consent.
• Willingness to allow storage of blood or tissue samples for future research
• Willingness at time of screening to undergo study procedures (phlebotomy, apheresis, optional FDG-PET/CT and lymph node biopsy\*)
• Willingness to have genetic testing
⁃ Participants should have a primary care physician or will need to agree to have one established by 24 weeks on study.
∙ In the event of an estimated reversible inability to consent, patients may enroll via a legally authorized representative (DPA) if they have the ability to assign a DPA. For these participants, baseline lymph node biopsy will not be performed however the week 4-8 lymph node biopsy may be performed if the participant regains the capacity to consent prior to that time. If a subject permanently loses the ability to consent during participation, they will be withdrawn from the study.
• Documentation of HIV-1 infection. Results from outside facilities will be accepted for enrollment.
• Meet criteria suspicious for IRIS (Must meet 4/5 following criteria):
• I. Initiation (reintroduction or change) in antiretroviral therapy/regimen
• II. Evidence of:
‣ an increase in CD4+ cell count defined as greater than or equal to 50cell/mm(3) or a greater than or equal to 2 fold rise in CD4+ cell count, and/or
‣ decrease in the HIV-1 viral load of greater than or equal to 0.5 log10
• III. Symptoms and/or signs consistent with an infectious/inflammatory condition.
• IV. Theses symptoms and/or signs cannot be explained by a newly acquired infection, the expected clinical course of a previously recognized infectious agent, or the side effects of antiretroviral therapy itself.
• V. The infectious/inflammatory condition must be attributable to a specific pathogen or condition.
• \*Criteria IV or V may not be met for suspected IRIS definition.
• Residence within the wider Washington D.C. area (within a 100-mile radius from the NIH Bethesda campus). \*\*Participants from outside of the 100 mile radius may be enrolled on a case by case basis to diagnose or manage IRIS.
• Men or women age greater than or equal to 18 years.
• Ability and willingness of subject to understand study requirements and give informed consent.
• Willingness to allow storage of blood or tissue samples for future research
• Willingness at time of screening to undergo study procedures (phlebotomy, apheresis, an optional FDG-PET/CT, and lymph node biopsy\*)
• Willingness to have genetic testing
• Participants should have a primary care physician who will initiate the referral.
‣ In the event of an estimated reversible inability to consent, patients may enroll using a legally authorized representative (DPA) if they have the ability to assign a DPA. lymph node biopsy will not be performed in these occasions. If a subject permanently loses the ability to consent during participation, they will be withdrawn from the study.