PET Imaging and Lymph Node Assessment of IRIS in People With AIDS

* ELIGIBILITY CRITERIA: ART NAIVE ARM INCLUSION CRITERIA: 1. Documentation of HIV-1 infection. Results from outside facilities will be accepted for enrollment. 2. 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 3. Documented CD4+ cell count \<=100 cells/mm\^3 within the past 8 weeks. 4. 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 5. Men or women age \>=18 years. 6. Ability and willingness of subject (or legal guardian/representative) to understand study requirements and give informed consent\*. 7. Willingness to allow storage of blood or tissue samples for future research 8. Willingness at time of screening to undergo study procedures (phlebotomy, apheresis, optional FDG-PET/CT and lymph node biopsy) 9. Willingness to have genetic testing 10. Participants should have a primary care physician or will need to agree to have one established by 24 weeks on study. * Potential participants who lack decision-making capacity to consent to research participation may enroll in this study at the discretion of the investigator if this incapacity is expected to last for a short period of time. IRIS ARM INCLUSION CRITERIA: 1. Documentation of HIV-1 infection. Results from outside facilities will be accepted for enrollment. 2. Meet criteria suspicious for IRIS (Must meet 4/5 following criteria): 1. Initiation (reintroduction or change) in antiretroviral therapy/regimen 2. Evidence of: i. an increase in CD4+ cell count defined as \>= 50cell/mm\^3 or a \>= 2 fold rise in CD4+ cell count, and/or ii. decrease in the HIV-1 viral load of \>=0.5 log10 c. Symptoms and/or signs consistent with an infectious/inflammatory condition. d. These 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. e. The infectious/inflammatory condition must be attributable to a specific pathogen or condition. Criteria d or e may not be met for suspected IRIS definition. 3. 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. 4. Men or women age \>=18 years. 5. Ability and willingness of subject to understand study requirements and give informed consent\*. 6. Willingness to allow storage of blood or tissue samples for future research 7. Willingness at time of screening to undergo study procedures (phlebotomy, apheresis, an optional FDG-PET/CT, and lymph node biopsy) 8. Willingness to have genetic testing 9. Participants should have a primary care physician who will initiate the referral. * Potential participants who lack decision-making capacity to consent to research participation may enroll in this study at the discretion of the investigator if this incapacity is expected to last for a short period of time. SUBJECT EXCLUSION CRITERIA: 1. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements. 2. Pregnancy will be an exclusion criterion for study entry given the intense nature of the protocol regarding blood draws, apheresis, biopsies and FDG-PET/CT imaging. 3. Inadequate venous access for phlebotomy and apheresis procedures as assessed by the study team. 4. Women who are breastfeeding. 5. A life-threatening underlying illness that according to the study team requires immediate intervention such as PML requiring initiation of ARVs or lymphomas requiring chemotherapy initiation. 6. An inability to consent that is estimated by the study team to be irreversible. 7. History of significant medical non-adherence which would, in the opinion of the investigator, interfere with study participation.