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

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Feb 10, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called lenacapavir to see if it can help people living with HIV who are already taking medications to keep the virus under control. The goal is to see if this treatment can reduce the hidden reservoirs of the virus in the body, which can help improve long-term health for those with HIV. The trial is currently recruiting participants aged 18 to 75 who have been on stable HIV treatment for at least three years and have a specific level of HIV in their blood.

To participate, individuals need to be in generally good health and willing to follow all study procedures. Participants will receive lenacapavir and will be monitored throughout the study. It’s important to note that individuals with certain health conditions, those who are pregnant or breastfeeding, or those taking specific medications may not be eligible. If you or someone you know meets the criteria and is interested in contributing to this important research, it could be a meaningful opportunity to help advance HIV treatment.

Gender

ALL

Eligibility criteria

• * INCLUSION CRITERIA:
• To be eligible to participate in this study, an individual must meet all of the following criteria:
• • 1. Able to provide informed consent.
• • 2. Stated willingness to comply with all study procedures and availability for the duration of the study.
• • 3. Aged 18 years to 75 years.
• • 4. 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.
• • 5. Confirmed HIV-1 infection.
• • 6. Total HIV DNA reservoir size greater than 300 copies/106 CD4+ T cells.
• • 7. CD4+ T cell count \>200 cells/mm\^3 at screening.
• 8. 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:
• • 1. The blips are \<=400 copies/mL.
• • 2. Succeeding viral levels return to below the limit of quantification (\<40 copies/mL) on subsequent testing.
• • 9. 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.
• 10. 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:
• • 1. Contraceptive subdermal implant.
• • 2. Intrauterine device or intrauterine system.
• • 3. Combined estrogen and progestogen oral contraceptive.
• • 4. Injectable progestogen.
• • 5. Contraceptive vaginal ring.
• • 6. Percutaneous contraceptive patches.
• • EXCLUSION CRITERIA
• An individual who meets any of the following criteria will be excluded from participation in this study:
• • 1. History of AIDS-defining illness within 3 years prior to enrollment.
• • 2. 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.
• • 3. 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.
• • 4. 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.
• • 5. Pregnancy or lactation.
• • 6. Any licensed vaccine (eg, hepatitis B, influenza, pneumococcal polysaccharide) received within 2 weeks prior to the study enrollment.
• • 7. 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.
• 8. Systemic immunosuppressive medications received within 3 months prior to enrollment. The following are not excluded:
• • 1. Corticosteroid nasal spray or inhaler.
• • 2. Topical corticosteroids for mild, uncomplicated dermatitis.
• • 3. 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).
• 9. History or other clinical evidence of:
• • 1. Significant or unstable cardiac disease (eg, angina, congestive heart failure, recent myocardial infarction).
• • 2. Severe illness, malignancy, or immunodeficiency other than HIV.
• • 3. Active systemic infection other than HIV.
• • 10. 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.
• 11. Laboratory abnormalities in the parameters listed below:
• • 1. Absolute neutrophil count \<1,000 cells/mm\^3
• • 2. Hemoglobin \<10 g/dL
• • 3. Platelet count \<100,000 cells/mm\^3
• • 4. ALT \>1.5 x ULN
• • 5. AST \>1.5 x ULN
• • 6. Total bilirubin \>1.5 x ULN
• • 7. Estimated glomerular filtration rate \<30 mL/min/1.73m\^2
• • 12. Inability to undergo leukapheresis due to poor venous access or other medical conditions.
• 13. Concurrent treatment with any of the medications listed below:
• • 1. Antiarrhythmics: digoxin
• • 2. Anticoagulants: direct oral anticoagulants (DOACs), rivaroxaban, dabigatran, edoxaban
• • 3. Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin
• • 4. Antiretroviral Agents: atazanavir/cobicistat, atazanavir/ritonavir, efavirenz, nevirapine, tipranavir/ritonavir
• • 5. Antimycobacterials: Rifabutin, rifampin, rifapentine
• • 6. Corticosteroids (systemic): dexamethasone, hydrocortisone/cortisone
• • 7. Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine
• • 8. Herbal products: St. John's wort c (Hypericum perforatum)
• • 9. HMG-CoA reductase inhibitors: lovastatin simvastatin
• • 10. Narcotic analgesics metabolized by CYP3A: fentanyl, oxycodone
• • 11. Tramadol
• • 12. Narcotic analgesic for treatment of opioid dependence: buprenorphine, methadone
• • 13. Opioid antagonist: naloxegol
• • 14. Phosphodiesterase-5 (PDE-5) inhibitors: sildenafil, tadalafil, vardenafil
• • 15. Sedatives/Hypnotics: midazolam (oral), triazolam
• • 14. Past or current medical findings that are not listed above, which, in the opinion of the investigator, may pose additional risk from participation in the study, may interfere with the individual's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study.