Combination Antiretroviral Therapy for HIV

Not currently recruiting at 42 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Gilead Sciences

Must be taking: Antiretrovirals

Disqualifiers: Immunosuppression, Hepatitis C, Hepatitis B, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new HIV treatment to determine its safety, effectiveness, and ease of use. Researchers aim to discover if a combination of antibodies (Teropavimab and Zinlirvimab) and the drug lenacapavir (available as an injection and a tablet) outperforms current pills for individuals with controlled HIV. The trial seeks participants who have maintained stable HIV treatment for at least a year, with no recent viral load issues. Participants will either switch to the new treatment or continue their current pills for comparison. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop your current medications, but it evaluates switching from your current antiretroviral therapy to a new regimen. It's best to discuss with the trial coordinators to understand if you need to stop or adjust your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that lenacapavir, teropavimab, and zinlirvimab are generally safe and well-tolerated. Studies have found that lenacapavir, available as both an injection and tablets, effectively reduces HIV levels in the blood with few side effects. One study showed that participants who received lenacapavir injections every six months remained HIV negative, demonstrating its safety.

For teropavimab and zinlirvimab, research indicates they are also well-tolerated when used with lenacapavir. In a study, people using these treatments did not experience serious side effects, and the combination effectively controlled HIV.

In summary, earlier studies suggest that using these treatments together is safe. They have been well-tolerated, with no major health issues reported so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard HIV treatments, which often rely on daily oral medications, the combination of lenacapavir, teropavimab, and zinlirvimab offers a novel approach with its unique delivery method and mechanism of action. Lenacapavir is noteworthy for its extended dosing schedule, as it is administered via injection every six months, potentially improving adherence compared to daily pills. Meanwhile, teropavimab and zinlirvimab are monoclonal antibodies delivered intravenously that work by neutralizing the HIV virus, adding a new layer of viral suppression. Researchers are excited because this combination could simplify treatment regimens and enhance efficacy, especially for those who struggle with daily medication adherence.

What evidence suggests that this trial's treatments could be effective for HIV?

Research has shown that the combination of lenacapavir, teropavimab, and zinlirvimab, which participants in one arm of this trial may receive, could effectively treat HIV-1 infection. Lenacapavir has significantly reduced HIV-1 levels in the body, maintaining long-term suppression. Teropavimab and zinlirvimab are specialized antibodies that target and neutralize various HIV strains. Studies indicate these antibodies help individuals adhere to their treatment and maintain prolonged control over the virus. Together, these treatments could offer a strong alternative to current HIV therapies. ^{1 3 6 7 8}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

This trial is for adults with HIV-1 who've had a stable viral load under 50 copies/mL for at least a year, no significant resistance to their current ART regimen, and CD4+ T-cell count over 200 cells/μL. They shouldn't have hepatitis B or C infections, require ongoing immunosuppression, or have had Stage 3 HIV illnesses.

Inclusion Criteria

My virus is sensitive to teropavimab and zinlirvimab based on recent tests.

I changed my HIV medication more than 28 days ago, not due to treatment failure.

I have been on a stable HIV medication regimen of up to 2 drug classes for over a year.

Exclusion Criteria

I currently have hepatitis B.

Evidence of hepatitis C virus (HCV) infection (prior infection cleared spontaneously or with treatment is acceptable)

I am on continuous medication to suppress my immune system due to another health condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Treatment

Participants receive either the combination of LEN, teropavimab, and zinlirvimab or continue their baseline oral ART

52 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension Phase

Participants with HIV-1 RNA < 50 copies/mL at Week 52 can opt into an extension phase to continue receiving the study drugs

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Lenacapavir Injection
• Lenacapavir Tablet
• Teropavimab
• Zinlirvimab

Trial Overview The study tests the effectiveness of switching from standard oral ART to a new regimen combining lenacapavir (LEN) with two antibodies, teropavimab and zinlirvimab. It measures if participants maintain low HIV RNA levels (<50 copies/mL) after this switch.

How Is the Trial Designed?

Group I: Randomized Phase Treatment Group 3: SBR Experimental Treatment 1 Intervention

Participants in Stay on Baseline Regimen (SBR) group will continue their baseline oral antiretroviral therapy (ART) up to Week 52. ART included drugs like bictegravir/emtricitabine/tenofovir alafenamide, darunavir/cobicistat/emtricitabine/tenofovir alafenamide, dolutegravir/abacavir lamivudine, and rilpivirine/emtricitabine/tenofovir alafenamide, administered as per standard of care.

Group II: Randomized Phase Treatment Group 1: LEN + TAB + ZAB Experimental Treatment 4 Interventions

Participants will receive loading dose of lenacapavir (LEN) 600 mg tablets, orally, on Day 1 and Day 2. They will receive LEN 927 mg subcutaneous (SC) injection along with teropavimab (TAB) 2550 mg intravenous (IV) infusion and zinlirvimab (ZAB) 2550 mg IV infusion on Day 1 and every 6 months (Q6M) up to Week 52 in the Randomized Phase.

Group III: Extension Phase: Treatment Group 1: LEN + TAB + ZAB Experimental Treatment 3 Interventions

At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL will be given the option to participate in the study extension phase. In the study extension phase, participants will continue to receive their randomized study drugs every 26 weeks.

Group IV: Extension Phase Treatment Group 3: SBR Experimental Treatment 4 Interventions

At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL and in the absence of confirmed virologic rebound throughout the Randomized Phase of the study will be given the option to participate in the Extension Phase to switch from oral ART to LEN, TAB and ZAB, every 26 weeks at the dose specified for Treatment Group 1.

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

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]

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]

Citations

1. 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.

2. gilead.com gilead.com/news/news-details/2025/yeztugo-lenacapavir-is-now-the-first-and-only-fda-approved-hiv-prevention-option-offering-6-months-of-protection

Yeztugo Lenacapavir Is Now the First and Only FDA ... Data show that ≥99.9% of participants who received Yeztugo in the Phase 3 PURPOSE 1 and PURPOSE 2 trials remained HIV negative. “This is a ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2411858

Twice-Yearly Lenacapavir for HIV Prevention in Men and ... We evaluated the safety and efficacy of twice-yearly subcutaneous lenacapavir for prevention of HIV infection in cisgender gay, bisexual, and other men.

4. who.int who.int/news/item/26-09-2024-long-acting-injectable-lenacapavir-continues-to-show-promising-results-for-hiv-prevention

Long-acting injectable lenacapavir continues to show ... Lenacapavir demonstrated a 96% reduction in HIV incidence compared to background HIV incidence (2.37 per 100 person-years) and was 89% more ...

5. 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 ...

6. academic.oup.com academic.oup.com/cid/article/80/3/566/7745000

Efficacy and Safety of Long-Acting Subcutaneous Lenacapavir ... Treatment with subcutaneous lenacapavir in combination with an OBR was well tolerated and resulted in a high rate of virological suppression over 104 weeks.

7. ema.europa.eu ema.europa.eu/en/documents/outside-eu-product-information/lenacapavir-gilead-product-information_en.pdf

lenacapavir-gilead-product-information_en.pdf - EMA All individuals must be screened for HIV-1 prior to initiating lenacapavir, prior to each subsequent injection, and additionally as clinically appropriate ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/lenacapavir-subcutaneous-route/description/drg-20543689

Lenacapavir (subcutaneous route) - Side effects & dosage This medicine will not cure HIV infection or AIDS. It works by lowering the amount of HIV in the blood and helps the immune system. This may help delay some of ...