This study is currently recruiting participants.
Number
000277-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: 100 Years
Referral Letter Required
No
Population Exclusion(s)
Children
Keywords
Human Immunodeficiency Virus; Antiretroviral Therapy; FDG-PET; Reservoir
Recruitment Keyword(s)
None
Condition(s)
HIV
Investigational Drug(s)
Investigational Device(s)
Intervention(s)
Other: Acute Treatment Interruption
Supporting Site
National Cancer Institute
Human immunodeficiency virus (HIV) infects CD4 T cells. There is no cure for HIV. People with HIV need to take daily medications called antiretroviral therapy (ART) to control their infection. ART stops HIV from infecting cells, but HIV does not go away. Some infected cells remain. If ART is stopped, then HIV levels will rise and infect more cells.
Objective:
To find where HIV-infected cells are located in the body, even when ART is keeping levels low.
Eligibility:
Adults aged 18 years or older who are undergoing ART for HIV infection.
Design:
Participants will be screened with a physical exam, including blood tests. They will be assigned to 1 of 2 groups:
One group will stay on ART. They will have 2 study visits: the first 45 days after screening, and the second 12 to 16 weeks later. They will have a PET/CT scan at each visit. A substance called a tracer will be injected into their arm. They will lie still on a table that moves through a doughnut-shaped machine. This process takes up to 2 hours.
The other group will stop ART for no more than 90 days. This group will have 3 PET/CT scans over 8 months. Once they stop ART, they will visit the clinic weekly for blood tests. After restarting ART, they will continue to visit the clinic weekly until their HIV level is safe.
All participants will have small samples of tissue taken from lymph nodes. They may also opt to provide semen samples or vaginal fluid. They may have samples taken of bone marrow or the fluid inside their spinal column.
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INCLUSION CRITERIA: Participants must meet all of the following criteria to be eligible for this study: 1. Aged >=18 years. 2. People with HIV-1 documented using US Food and Drug Administration-approved screening and confirmatory or supplemental assays in Centers for Disease Control and Prevention (CDC)-recommended testing strategies. 3. Established medical care outside NIH. 4. Able to provide informed consent. 5. Willing to allow samples to be stored for future research. 6. Willing to allow genetic testing. 7. Undergoing cART using recommended, alternative, or other regimens as defined by Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. 8. Viral RNA <40 copies/mL plasma by conventional assay for at least 3 years (blips [transient increases within 6 weeks] of <200 copies/mL are allowable when succeeding viral levels return to <40 copies/mL on subsequent testing). 9. CD4 cell count >=350 cells/microliter. 10. Willing to interrupt ART for up to 90 days. 11. Willing to use a barrier method of contraception, such as condoms or dental dams, when engaging in sexual activity, or remain abstinent during ATI and after re-initiating ART until viral re-suppression is achieved, to prevent pregnancy and transmission of HIV. EXCLUSION CRITERIA: Participants who meet any of the following criteria will be excluded from this study: 1. Active intercurrent illness or infection, including fever >38 degrees Celsius. 2. Known history of initiating ART during the first year of infection with HIV. Participants will be considered to have initiated ART within 1 year of infection as defined by documented screening/confirmatory seroconversion (positive testing within one year of non-reactive HIV enzyme-linked immunosorbent assay). 3. Pregnant. 4. Breastfeeding. 5. Currently undergoing therapy with drugs that, in the judgment of the investigators, may interfere with biodistribution of FDG, including prednisolone, valproate carbamazepine, phenytoin, phenobarbital, and catecholamines. 6. Undergoing ART that is incompatible with an ATI. 7. Has undergone PET/CT within the last 6 months. 8. History of poorly controlled diabetes that, in the judgement of the investigators, would prevent completion of PET/CT scan. 9. Vaccination within the previous 4 weeks. 10. History of ATI within the past 1 year. 11. Has comorbid illness for which, in the judgment of the investigators, an ATI will represent elevated risk. 12. Active opportunistic infection as defined by the Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. 13. Significant active substance abuse or psychiatric illness that may, in the judgment of the investigator, interfere with study visits or procedures. 14. Allergy to planned anesthetic agents that are expected to be used. For local anesthetics, this is lidocaine. For sedation, this is midazolam and fentanyl. 15. Currently undergoing chronic systemic steroid therapy (corticosteroid nasal spray or inhaler and topical steroid use are acceptable). 16. Contraindication to use of IV contrast. 17. History of developing keloids. 18. Renal impairment: HIV-related kidney disease or estimated glomerular filtration rate (eGFR) CKD-EPI equation <60 mL/min/1.73 m^2. For individuals undergoing therapy with cobicistat or integrase strand inhibitors, GFR may be estimated using cystatin C or creatinine. 19. Active or chronic hepatitis B virus infection, with detectable hepatitis B surface antigen, hepatitis B virus DNA, or both. 20. Active hepatitis C virus infection, with detectable virus RNA. 21. History of HIV-associated dementia or progressive multifocal leukoencephalopathy. 22. Documented ARV drug resistance that, in the judgment of the investigator, would pose a risk of virologic failure should additional mutations develop during the study. 23. History of cardiovascular event or at high risk of an event (eg, atherosclerotic cardiovascular disease score >20%) (https://tools.acc.org/ascvd-risk-estimatorplus/#!/calculate/estimate/). 24. History of AIDS-defining illness according to CDC criteria within the past 3 years. 25. Hepatic impairment: alanine transaminase >2.5 X the upper limit of normal or documented history of cirrhosis. 26. Any condition that, in the judgment of the investigator, contraindicates participation in this study.
Participants must meet all of the following criteria to be eligible for this study:
1. Aged >=18 years.
2. People with HIV-1 documented using US Food and Drug Administration-approved screening and confirmatory or supplemental assays in Centers for Disease Control and Prevention (CDC)-recommended testing strategies.
3. Established medical care outside NIH.
4. Able to provide informed consent.
5. Willing to allow samples to be stored for future research.
6. Willing to allow genetic testing.
7. Undergoing cART using recommended, alternative, or other regimens as defined by Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV.
8. Viral RNA <40 copies/mL plasma by conventional assay for at least 3 years (blips [transient increases within 6 weeks] of <200 copies/mL are allowable when succeeding viral levels return to <40 copies/mL on subsequent testing).
9. CD4 cell count >=350 cells/microliter.
10. Willing to interrupt ART for up to 90 days.
11. Willing to use a barrier method of contraception, such as condoms or dental dams, when engaging in sexual activity, or remain abstinent during ATI and after re-initiating ART until viral re-suppression is achieved, to prevent pregnancy and transmission of HIV.
EXCLUSION CRITERIA:
Participants who meet any of the following criteria will be excluded from this study:
1. Active intercurrent illness or infection, including fever >38 degrees Celsius.
2. Known history of initiating ART during the first year of infection with HIV. Participants will be considered to have initiated ART within 1 year of infection as defined by documented screening/confirmatory seroconversion (positive testing within one year of non-reactive HIV enzyme-linked immunosorbent assay).
3. Pregnant.
4. Breastfeeding.
5. Currently undergoing therapy with drugs that, in the judgment of the investigators, may interfere with biodistribution of FDG, including prednisolone, valproate carbamazepine, phenytoin, phenobarbital, and catecholamines.
6. Undergoing ART that is incompatible with an ATI.
7. Has undergone PET/CT within the last 6 months.
8. History of poorly controlled diabetes that, in the judgement of the investigators, would prevent completion of PET/CT scan.
9. Vaccination within the previous 4 weeks.
10. History of ATI within the past 1 year.
11. Has comorbid illness for which, in the judgment of the investigators, an ATI will represent elevated risk.
12. Active opportunistic infection as defined by the Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV.
13. Significant active substance abuse or psychiatric illness that may, in the judgment of the investigator, interfere with study visits or procedures.
14. Allergy to planned anesthetic agents that are expected to be used. For local anesthetics, this is lidocaine. For sedation, this is midazolam and fentanyl.
15. Currently undergoing chronic systemic steroid therapy (corticosteroid nasal spray or inhaler and topical steroid use are acceptable).
16. Contraindication to use of IV contrast.
17. History of developing keloids.
18. Renal impairment: HIV-related kidney disease or estimated glomerular filtration rate (eGFR) CKD-EPI equation <60 mL/min/1.73 m^2. For individuals undergoing therapy with cobicistat or integrase strand inhibitors, GFR may be estimated using cystatin C or creatinine.
19. Active or chronic hepatitis B virus infection, with detectable hepatitis B surface antigen, hepatitis B virus DNA, or both.
20. Active hepatitis C virus infection, with detectable virus RNA.
21. History of HIV-associated dementia or progressive multifocal leukoencephalopathy.
22. Documented ARV drug resistance that, in the judgment of the investigator, would pose a risk of virologic failure should additional mutations develop during the study.
23. History of cardiovascular event or at high risk of an event (eg, atherosclerotic cardiovascular disease score >20%) (https://tools.acc.org/ascvd-risk-estimatorplus/#!/calculate/estimate/).
24. History of AIDS-defining illness according to CDC criteria within the past 3 years.
25. Hepatic impairment: alanine transaminase >2.5 X the upper limit of normal or documented history of cirrhosis.
26. Any condition that, in the judgment of the investigator, contraindicates participation in this study.
Principal Investigator
Referral Contact
For more information: