Lenacapavir Intensification to Disrupt HIV Reservoirs in Virologically Suppressed People Living With HIV Receiving Antiretroviral Therapy
Background: Antiretroviral viral therapy (ART) allows people living 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. ...
⁃ 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 \<=400 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.
∙ Combined estrogen and progestogen oral contraceptive.
∙ Injectable progestogen.
∙ Contraceptive vaginal ring.
∙ Percutaneous contraceptive patches.