Lenacapavir Intensification to Disrupt HIV Reservoirs in Virologically Suppressed People With HIV Receiving Antiretroviral Therapy

NCT06819176 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10002211002211-I
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Antiretroviral viral therapy (ART) allows people with human immunodeficiency (HIV) to live long, healthy lives. But ART is not a cure. HIV can remain in the body, in infected cells called reservoirs. If a person stops taking ART, the HIV can rebound and reach high levels in their blood. Researchers want to find ways to reduce the size of HIV reservoirs in people taking ART. Objective: To test a drug (lenacapavir) in people with HIV who are on effective ART. Lenacapavir, also called Sunlenca, is already approved for use in people with HIV who cannot be treated with standard ART. Eligibility: People aged 18 to 75 years with HIV that has been suppressed for at least 3 years with ART. Design: Participants will have 13 clinic visits over 2 years. Participants will be screened. They will have a physical exam with blood tests. They will maintain their ART throughout the study. Participants will undergo leukapheresis up to 6 times. Blood will be drawn via a tube in an arm. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be returned to the body through a second tube. Two-thirds of participants will take lenacapavir in addition to their regular ART. They will receive the drug as an injection under the skin 3 times at 6-month intervals. They will also take lenacapavir as 2 pills swallowed by mouth on the first 2 days of the study. ...

Conditions

Human Immunodeficiency Virus

Keywords

HIV; ART intensification; Reservoir; lenacapavir; persistence

Outcome Measures

Primary Outcomes (1)

• Changes in the intact HIV proviral reservoir size, measured by IPDA in the blood CD4+ T-cell compartment from baseline to weeks 12, 24, 48, 72, and 96.

  To compare the effect of the presence or absence of lenacapavir on intact HIV proviral DNA reservoirs in PWH who had been receiving virologically suppressive (\<40 copies/mL) ART for greater than 3 years.

  Through week 96.

Secondary Outcomes (1)

• Changes in the residual HIV plasma viremia (1-39 copies/mL) from baseline to weeks 12, 24, 48, 72, and 96 in the lenacapavir and control arm.

  Through week 96.

Study Arms (2)

Interventional

EXPERIMENTAL

Participants will receive lenacapavir at 927 mg by subcutaneous injection (2x1.5 mL injections) on day 0 and 600 mg orally (2x300 mg tablets) on days 0 and 1, followed by 927 mg by subcutaneous injection (2x1.5 mL injections) at weeks 24 and 48.

Drug: Lenacapavir

Standard of Care

NO INTERVENTION

Participants who are not randomized to lenacapavir will remain on their current ART regimens.

Interventions

Lenacapavir DRUG

Lenacapavir (Sunlenca) is a prescription drug approved by the Food and Drug Administration (FDA) for the treatment of people living with multidrug-resistant HIV. Lenacapavir is always used as part of a combination ART regimen. Participants will receive lenacapavir at 927 mg by subcutaneous injection (2x1.5 mL injections) on day 0 and 600 mg orally (2x300 mg tablets) on days 0 and 1, followed by 927 mg by subcutaneous injection (2x1.5 mL injections) at weeks 24 and 48.

Interventional

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all of the following criteria:
• Able to provide informed consent.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Aged 18 years to 75 years.
• In generally good health with an identified primary health care provider for medical management of HIV infection and willing to maintain a relationship with a primary health care provider while participating in the study.
• Confirmed HIV-1 infection.
• Total HIV DNA reservoir size greater than 300 copies/106 CD4+ T cells.
• CD4+ T cell count \>200 cells/mm\^3 at screening.
• Documentation of continuous ART treatment \>3 years with suppression of plasma viral level below the limit of quantitation (\<40 copies/mL). Individuals with \<= 2 blips (\>40 copies/mL) over 48 weeks prior to screening may be included provided they satisfy the following criteria:
• The blips are \<=200 copies/mL.
• Succeeding viral levels return to below the limit of quantification (\<40 copies/mL) on subsequent testing.
• For individuals who can become pregnant (ie, participants who have not been postmenopausal 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), must have a negative pregnancy test at screening and within 48 hours prior to day 0. 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 1 acceptable method of contraception when engaging in sexual activities that can result in pregnancy from 10 days prior to the first dose of lenacapavir through study follow up. Acceptable methods of contraception include the following:
• Contraceptive subdermal implant.
• Intrauterine device or intrauterine system.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• History of AIDS-defining illness within 3 years prior to enrollment.
• History of systemic corticosteroids (eg, 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 principal investigator within the last 6 months.
• Any clinically significant acute or chronic medical condition (eg, 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.
• Hepatitis B or C infection as indicated by the presence of hepatitis B surface antigen or hepatitis C virus (HCV) RNA in blood.
• NOTE: Participants with a positive test for HCV antibody and a negative test for HCV RNA are eligible.
• Pregnancy or lactation.
• Any licensed vaccine (eg, hepatitis B, influenza, pneumococcal polysaccharide) received within 2 weeks prior to the study enrollment.
• Receipt of other investigational study agents within 28 days of enrollment and at any time during the study, including any experimental non-HIV vaccination within 2 weeks prior to enrollment.
• Systemic immunosuppressive medications received within 3 months prior to enrollment. The following are not excluded:
• Corticosteroid nasal spray or inhaler.
• Topical corticosteroids for mild, uncomplicated dermatitis.
• Oral/parenteral corticosteroids administered for non-chronic conditions not expected to recur (length of therapy 10 days, with completion in 30 days prior to enrollment).
• Cyclosporine eye drops
• Active drug or alcohol abuse or any other pattern of behavior that, in the opinion of the investigator, would interfere with adherence to study requirements.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

lenacapavir

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 Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kathleen R Gittens

CONTACT

(301) 435-8003; kathleen.gittens@nih.gov

Chuen-Yen C Lau, M.D.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: February 8, 2025
• First Posted: February 11, 2025
• Study Start: January 20, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): January 24, 2029
• Last Updated: April 20, 2026

Record last verified: 2026-04-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: At the time of publication.
• Access Criteria: Per repository and NIH Data Sharing requirements.

Locations

US (1)