Imaging and Biopsy of People With HIV-1 Undergoing Analytic Treatment Interruption

NCT05419024 | Recruiting Phase 2

• 2 other identifiers: 10000277000277-C
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Background: 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 compare changes in the amount of virus in blood and lymph nodes after a short treatment interruption. 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....

Conditions

HIV

Keywords

Human Immunodeficiency Virus; Antiretroviral Therapy; FDG-PET; Reservoir

Outcome Measures

Primary Outcomes (1)

• Fold increase in HIV nucleic acids (RNA and DNA) in blood or lymphoid compartments from baseline to 10 day ATI vs baseline to no ATI.

  Compare change in HIV DNA and RNA after 10 day ATI in peripheral circulation and lymphoid compartment.

  Up to day 90

Secondary Outcomes (6)

• 6. Correlation of HIV RNA levels and cytokine and T-cell profiles.

  Up to Month 6

• 5. HIV RNA and DNA sequence analyses for genetic studies and potential for replication.

  Up to Month 6

• 4. Cytokine and T-cell profiles during suppression and after ATI criteria for treatment resumption are met.

  Up to Month 6

• 3. Correlation between regional and overall change in 18F uptake with HIV DNA and RNA sequencing characteristics pre-ATI to post ATI.

  Up to Month 6

• 2. Change in levels of HIV DNA, structure of HIV populations, and integration site distribution to assess clonal distribution at different biopsy sites, semen, vaginal fluid, and PBMCs. And following ATI, and after ART resumption.

  Up to Month 6

Study Arms (2)

ATI

EXPERIMENTAL

Participants randomized to ATI will halt their ART medications starting 2 weeks (more or less 3 days) after the first imaging visit. This plan will be discussed with participants during the baseline visit. Patients will be contacted 1-3 days prior to ATI initiation. ATI may be delayed or cancelled if there are new safety concerns. HIV plasma viral levels and CD4 counts will be monitored every week during the ATI phase. If a participant meets any of the ART restart criteria during the ATI phase, then they will discontinue ATI and restart ART. Participants who do not meet restart criteria will remain off ART and continue to be monitored weekly until they have been on ATI for 90 days, and then will restart ART.

Other: Acute Treatment Interruption

Continue ART

NO INTERVENTION

Participants will continue on their pre-study ART throughout the trial.

Interventions

Acute Treatment Interruption OTHER

Participants randomized to ATI will halt their ART medications starting 2 weeks (more or less 3 days) after the first imaging visit. This plan will be discussed with participants during the baseline visit. Patients will be contacted 1-3 days prior to ATI initiation. ATI may be delayed or cancelled if there are new safety concerns. HIV plasma viral levels and CD4 counts will be monitored every week during the ATI phase. If a participant meets any of the ART restart criteria during the ATI phase, then they will discontinue ATI and restart ART. Participants who do not meet restart criteria will remain off ART and continue to be monitored weekly until they have been on ATI for 90 days, and then will restart ART.

ATI

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria to be eligible for this study:
• Aged \>=18 years.
• 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.
• Established medical care outside NIH.
• Able to provide informed consent.
• Willing to allow samples to be stored for future research.
• Willing to allow genetic testing.
• Undergoing cART using recommended, alternative, or other regimens as defined by "Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV."
• 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).
• CD4 cell count \>=350 cells/microliter.
• Willing to interrupt ART for up to 90 days.
• 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.

You may not qualify if:

• Participants who meet any of the following criteria will be excluded from this study:
• Active intercurrent illness or infection, including fever \>38 degrees Celsius.
• 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).
• Pregnant.
• Breastfeeding.
• 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.
• Undergoing ART that is incompatible with an ATI.
• Has undergone PET/CT within the last 6 months.
• History of poorly controlled diabetes that, in the judgement of the investigators, would prevent completion of PET/CT scan.
• Vaccination within the previous 4 weeks.
• History of ATI within the past 1 year.
• Has comorbid illness for which, in the judgment of the investigators, an ATI will represent elevated risk.
• Active opportunistic infection as defined by the Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV.
• Significant active substance abuse or psychiatric illness that may, in the judgment of the investigator, interfere with study visits or procedures.
• Allergy to planned anesthetic agents that are expected to be used. For local anesthetics, this is lidocaine. For sedation, this is midazolam and fentanyl.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (2)

• Lau CY, Adan MA, Maldarelli F. Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection. Viruses. 2021 Dec 14;13(12):2512. doi: 10.3390/v13122512.

  PMID: 34960781 BACKGROUND

• Lau CY, Adan MA, Earhart J, Seamon C, Nguyen T, Savramis A, Adams L, Zipparo ME, Madeen E, Huik K, Grossman Z, Chimukangara B, Wulan WN, Millo C, Nath A, Smith BR, Ortega-Villa AM, Proschan M, Wood BJ, Hammoud DA, Maldarelli F. Imaging and biopsy of HIV-infected individuals undergoing analytic treatment interruption. Front Med (Lausanne). 2022 Aug 22;9:979756. doi: 10.3389/fmed.2022.979756. eCollection 2022.

  PMID: 36072945 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Chuen-Yen C Lau, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chuen-Yen C Lau, M.D.

CONTACT

(240) 858-7088; lauc@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2022
• First Posted: June 15, 2022
• Study Start: January 9, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04-29

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)