Immunologic and Virologic Parameters During Analytical Treatment Interruption Following Combination bNAb Therapy During Suppressive ART

NCT06908083 | Enrolling By Invitation Phase 1

• 2 other identifiers: 10002295002295-I
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Background: Recent studies have shown bNAbs may help remove cells that are infected with HIV (HIV reservoir) from the body and may also change how the immune system fights HIV. Objective: The purpose of this research study is to see if and when HIV levels in the blood (viral load) rise after the participant stops their HIV medication. We will also measure the highest number (peak) of the virus before each participant starts their HIV medications again. For most people treated with standard HIV medications, the HIV virus amount will increase within 2 to 4 weeks after stopping their HIV medications. This study is only open to participants who have taken part in an earlier study (MCA-1034 or NIH number 001037). In the earlier study, participants either received a combination of 3BN117-LS and 10-1074-LS (two anti-HIV monoclonal antibodies) OR received placebo (salt water). In this new study, researchers will compare the participants who received the antibodies to those who did not to see what effect the antibodies may have had on the HIV reservoir. Researchers will also look at:

• side effects people may have when they stop their HIV medications.
• changes in the number of blood cells carrying inactive HIV (the HIV reservoir size).
• the blood cells that can clear HIV before, following temporarily stopping, and after re-starting HIV medications.
• how well HIV may be controlled after a participant stops their HIV medication. Eligibility: People aged 18 to 70 years with HIV who completed protocol MCA-1034 (NIH Study 001037). Design: Participants will be screened. They will have a physical exam. They will answer questions about their health. Blood samples will be taken. Participants will stop their HIV medications for a period of time. They will have blood tests every 2 weeks and clinic visits every 4 weeks for 24 weeks to check their HIV levels and to make sure they are not having side effects. There will be strict safety rules for restarting HIV medications. Some participants whose HIV levels remain low at 24 weeks may continue without ART for another 24 weeks; they will have blood tests every 2 to 4 weeks. Participants may undergo leukapheresis up to 3 times: Leukapheresis is a several hours long procedure in which blood is collected from a vein in one arm, processed through an attached machine, and then returned to the person through a vein in the opposite arm. Participants will have 4 follow-up visits over 24 weeks after they restart ART. Participants will remain in the study up to 18 months.

Conditions

HIV

Keywords

HIV Infection; Analytical Treatment Interruption; bnab therapy

Outcome Measures

Primary Outcomes (1)

• Time to Restart ART

  Difference in number of days from stopping ART (Day 0) until participant meets restart criteria between MCA-1034/001037 (NIH) bNAb and placebo recipients

  Week 0 until Week 48 or when participant meets restart criteria

Secondary Outcomes (6)

• Difference in Peak Plasma Viremia

  Week 0 until Week 48 or when participant meets restart criteria

• Frequency of Grade 3 or higher Adverse Events

  Week 0 until Week 48 or when participant meets restart criteria

• Frequency of Serious Adverse Events

  Week 0 until Week 48 or when participant meets restart criteria

• Change in intact proviral reservoir size

  Throughout

• Changes in HIV-1 Specific T Cell Immune Responses in Peripheral Blood

  Throughout

Study Arms (1)

Adults living with HIV

EXPERIMENTAL

Participants who received either two intravenous infusions of 3BNC117-LS (dosed at 30 mg /kg) and 10-1074-LS (dosed at 10 mg/kg) or two saline infusions (placebo) at weeks 0, and 20 as part of the Rockefeller University trial (MCA-1034) or the NIH trial (001037) and are willing to interrupt treatment and then restart once criteria is met.

Other: Analytical Treatment Interruption

Interventions

Analytical Treatment Interruption OTHER

Participants will stop their ART (Antiretroviral therapy) on Week 0 and will remain off of their ART for up to 48 weeks or until they meet restart criteria.

Adults living with HIV

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Ability to provide informed consent;
• Stated willingness to comply with all study procedures and availability for the duration of the study;
• Adult persons of any sex, aged 18 years to 70;
• Participated in Protocol MCA-1034 (NIH # 001037) and completed follow up 12 to 24 weeks prior to study entry (day 0);
• On antiretroviral therapy with plasma HIV-1 RNA levels of less than or equal to 50 copies/ml and no reported interruption of ART for 7 consecutive days or longer for at least 48 weeks.
• NOTE: A single plasma HIV-1 RNA \>50 copies/mL but less than 200 copies/mL that is followed by an HIV-1 RNA \<= 50 copies/mL is permitted;
• Current CD4+ T cell counts \>= 400 cells/mcL, CD4+ T cell % \>= 15%;
• If on an NNRTI-based regimen, willing to switch to an integrase or protease inhibitor-based regimen for at least 4 weeks prior to discontinuing ART;
• For participants who can become pregnant (i.e., participants who have not been post-menopausal for at least 24 consecutive months, who have had menses within the preceding 24 months, or who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy), negative pregnancy test at screening and within 48 hours prior to entry.
• NOTE: Participant-reported history is acceptable as documentation of hysterectomy and bilateral oophorectomy, tubal ligation, tubal micro-inserts, and vasectomy;
• Participants who can become pregnant must agree to use one method of contraception, from the highly effective methods for contraception listed below. Barrier methods of contraception are permitted as a method of contraception. Contraception must be used from study entry and until ART is reinitiated and viral suppression is achieved. Acceptable methods of contraception include:
• Condom with spermicide
• Diaphragm with spermicide
• Contraceptive subdermal implant

You may not qualify if:

• Any individual who meets any of the following criteria will be excluded from participation in this study:
• History of AIDS-defining illness and/or known CD4 nadir less than 100 cells/mcL in the last 3 years;
• History of systemic corticosteroids (e.g. an equivalent dose of prednisone of \>20 mg daily for \>14 days), immunosuppressive anti-cancer, interleukins, systemic interferons, systemic chemotherapy or other medications considered significant by the trial physician within the last 3 months;
• Any clinically significant acute or chronic medical condition (e.g. such as autoimmune diseases, cirrhosis, active malignancy that may require systemic chemotherapy or radiation therapy), other than HIV infection, that in the opinion of the investigator would preclude participation;
• History of or current clinical atherosclerotic cardiovascular disease (ASCVD), as defined by 2018 ACC/AHA guidelines, including a previous diagnosis of any of the following:
• Acute myocardial infarction
• Acute coronary syndromes
• Stable or unstable angina
• Coronary or other arterial revascularization procedures
• Stroke
• Transient ischemic attack
• Peripheral arterial disease presumed to be of atherosclerotic origin;
• Any history of an HIV-associated malignancy, including Kaposi's sarcoma, or any type of lymphoma or virus-associated cancers;
• Any history of Progressive Multifocal Leukoencephalopathy (PML);
• Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or isolated positive HBV core antibody or hepatitis C virus RNA (HCV-RNA) in blood; NOTE: Participants with a positive test for HCV antibody and a negative test for HCV RNA are eligible; as are participants with isolated HBcAb who are receiving an ART regimen that do not include tenofovir (TAF or TDF).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Rockefeller Institute

New York, New York, 10065, United States

Location

Related Publications (3)

• Clarridge KE, Blazkova J, Einkauf K, Petrone M, Refsland EW, Justement JS, Shi V, Huiting ED, Seamon CA, Lee GQ, Yu XG, Moir S, Sneller MC, Lichterfeld M, Chun TW. Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals. PLoS Pathog. 2018 Jan 11;14(1):e1006792. doi: 10.1371/journal.ppat.1006792. eCollection 2018 Jan.

  PMID: 29324842 BACKGROUND

• Sneller MC, Huiting ED, Clarridge KE, Seamon C, Blazkova J, Justement JS, Shi V, Whitehead EJ, Schneck RF, Proschan M, Moir S, Fauci AS, Chun TW. Kinetics of Plasma HIV Rebound in the Era of Modern Antiretroviral Therapy. J Infect Dis. 2020 Oct 13;222(10):1655-1659. doi: 10.1093/infdis/jiaa270.

  PMID: 32443148 BACKGROUND

• Sneller MC, Blazkova J, Justement JS, Shi V, Kennedy BD, Gittens K, Tolstenko J, McCormack G, Whitehead EJ, Schneck RF, Proschan MA, Benko E, Kovacs C, Oguz C, Seaman MS, Caskey M, Nussenzweig MC, Fauci AS, Moir S, Chun TW. Combination anti-HIV antibodies provide sustained virological suppression. Nature. 2022 Jun;606(7913):375-381. doi: 10.1038/s41586-022-04797-9. Epub 2022 Jun 1.

  PMID: 35650437 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

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

Study Officials

• Michael C Sneller, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2025
• First Posted: April 3, 2025
• Study Start: September 8, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: May 14, 2026

Record last verified: 2026-05-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Within one year of primary completion date of final subject

Locations

US (2)