Lenacapavir for HIV

Overseen By Chuen-Yen C Lau, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: ART

Must not be taking: Anticoagulants, Anticonvulsants, Antiretrovirals, others

Disqualifiers: AIDS, Hepatitis B/C, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 12

Duration: 48 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called lenacapavir to determine if it can reduce the number of HIV-infected cells, known as "reservoirs," in individuals already on effective antiretroviral therapy (ART). While ART can control HIV, it doesn't eliminate it, and the virus can return if ART is stopped. Researchers aim to discover if adding lenacapavir can target these hidden virus reservoirs. Candidates for this trial have had their HIV suppressed by ART for at least three years. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering a chance to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial requires you to stop taking certain medications, including specific antiarrhythmics, anticoagulants, anticonvulsants, antiretroviral agents, antimycobacterials, systemic corticosteroids, ergot derivatives, herbal products like St. John's wort, certain cholesterol medications, some narcotic analgesics, opioid dependence treatments, opioid antagonists, PDE-5 inhibitors, and certain sedatives. If you are on any of these, you may need to stop them to participate in the trial.

Is there any evidence suggesting that lenacapavir is likely to be safe for humans?

Research has shown that lenacapavir is generally safe for people with HIV. In one study, participants who took lenacapavir with other HIV medications for 104 weeks mostly did not experience serious side effects. Another study found that both the injection and pill forms of lenacapavir were safe and well-tolerated by participants. These findings suggest that lenacapavir is safe for use alongside regular HIV treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Lenacapavir is unique because it offers a novel approach to treating HIV with its long-acting formulation and innovative delivery method. Unlike the standard of care, which typically involves daily oral antiretroviral therapies, lenacapavir is administered through subcutaneous injections only a few times a year. This could significantly improve adherence and convenience for patients. Researchers are excited about lenacapavir because it targets a specific stage of the HIV life cycle, potentially leading to better outcomes and fewer side effects compared to existing treatments.

What evidence suggests that lenacapavir might be an effective treatment for HIV?

In this trial, participants will receive lenacapavir, which studies have shown effectively controls HIV when administered as an injection twice a year. It helps maintain low virus levels in people with HIV. A previous study demonstrated that lenacapavir completely prevented new HIV cases compared to standard treatments. Additionally, lenacapavir is already approved for individuals with HIV who cannot use regular antiretroviral therapy (ART), suggesting it can be a strong option for managing HIV alongside other treatments. Participants not receiving lenacapavir in this trial will continue their current ART regimens. ^{1 2 3 6 7}

Who Is on the Research Team?

Chuen-Yen C Lau, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with HIV who are in good health, have been on antiretroviral therapy (ART) for over 3 years with a suppressed viral load, and have a CD4+ T cell count above 200. They must not be pregnant or breastfeeding and agree to use contraception. Exclusions include recent illness, drug abuse, certain medication use, other infections like hepatitis B/C, and inability to undergo leukapheresis.

Inclusion Criteria

Able to provide informed consent

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

Exclusion Criteria

Laboratory abnormalities in specified parameters

I have not had an AIDS-defining illness in the last 3 years.

Pregnancy or lactation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenacapavir intensification or continue ART alone

48 weeks

Injections at weeks 0, 24, and 48; oral doses on days 0 and 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 weeks

Visits at weeks 12, 24, 48, 72, and 96

What Are the Treatments Tested in This Trial?

Interventions

• Lenacapavir

Trial Overview The trial is testing Lenacapavir's ability to disrupt HIV reservoirs in people whose virus is already under control with ART. Participants will receive Lenacapavir intensification alongside their current treatment regimen to assess its impact on the size of the HIV reservoir.

How Is the Trial Designed?

Group I: Interventional Experimental Treatment 1 Intervention

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.

Group II: Standard of Care Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Lenacapavir is the first FDA-approved capsid inhibitor for treating multidrug-resistant HIV-1, specifically for heavily treatment-experienced adults whose current therapies are failing due to resistance or safety issues.

In a phase 3 clinical trial, lenacapavir significantly reduced viral load compared to placebo, and it is administered as a long-acting injection every 6 months, although 63% of participants experienced injection site reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenacapavir: A first-in-class capsid inhibitor for the treatment of highly treatment-resistant HIV. Prather, C., Lee, A., Yen, C.[2023]

Lenacapavir (LEN) is a novel capsid inhibitor that offers a unique treatment option for heavily treatment-experienced (HTE) HIV-1 patients, demonstrating efficacy in achieving viral suppression and immune restoration when combined with other antiretrovirals.

Administered subcutaneously twice a year, lenacapavir provides a convenient dosing schedule, making it a well-tolerated and effective addition to existing HIV treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenacapavir: A Novel Long-Acting Capsid Inhibitor for HIV. Tailor, MW., Chahine, EB., Koren, D., et al.[2023]

Citations

1. gilead.com gilead.com/news/news-details/2024/full-efficacy-and-safety-results-for-gilead-investigational-twice-yearly-lenacapavir-for-hiv-prevention-presented-at-aids-2024

Full Efficacy and Safety Results for Gilead Investigational ... Additionally, compared to once-daily Truvada, lenacapavir reduced HIV incidence by 100%, a result that was statistically superior (IRR 0; 95% CI ...

2. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2411858

Twice-Yearly Lenacapavir for HIV Prevention in Men and ... Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of human immunodeficiency virus (HIV) infection in cisgender women.

3. who.int who.int/news/item/19-06-2025-fda-approval-of-injectable-lenacapavir-marks-progress-for-hiv-prevention

FDA approval of injectable lenacapavir marks progress for ... Administered just twice a year, lenacapavir offers sustained protection and adds to the growing range of HIV prevention options. WHO currently ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39206943/

Week 104 Results of a Phase 2/3 Trial Treatment with subcutaneous lenacapavir in combination with an OBR was well tolerated and resulted in a high rate of virological suppression over 104 weeks.

5. thelancet.com thelancet.com/journals/lanam/article/PIIS2667-193X(25)00156-5/fulltext

Lenacapavir: a potential game changer for HIV prevention ... In PURPOSE 2, lenacapavir had a 96% efficacy for PrEP compared to the background HIV incidence and was superior to F/TDF among men who have sex ...

6. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-67362500405-2/abstract

Pharmacokinetics and safety of once-yearly lenacapavir Both formulations were safe and well tolerated. These data show the potential for biomedical HIV prevention with a once-yearly dosing interval.

7. cdc.gov cdc.gov/mmwr/volumes/74/wr/mm7435a1.htm

Clinical Recommendation for the Use of Injectable ... The two trials reported LEN efficacy at reducing HIV infection as 100% among females and 96% among a primarily male trial population, compared ...