Switching to Lenacapavir, Teropavimab, and Zinlirvimab in Virologically Suppressed Adults with HIV-1: A Phase 3 Randomized Study

3 1 1 1

What is this study about?

The study focuses on adults living with HIV-1 who already have the virus under control with daily oral medicines. The new approach replaces those pills with an injection given twice a year that contains three agents: lenacapavir, a medication that blocks the virus’s protective shell (the capsid); teropavimab and zinlirvimab, which are lab‑made antibodies that attach to the virus and prevent it from infecting cells.

The purpose of the study is to see whether switching to this injection regimen keeps the virus suppressed as well as continuing the usual oral pills. Participants will receive the injection at the start of the study and then every six months, while regular clinic visits will collect blood samples to check the amount of virus, the number of CD4+ T‑cells (a type of immune cell that helps fight infections), and any changes in health over about two years.

Throughout the trial, safety will be closely watched. Any side effects or problems will be recorded, and participants may stop the study medication if serious issues arise. Blood tests will also measure how much of the new drugs remain in the body and whether the body develops any antibodies against them.

1 baseline visit and first dosing

at week 0 you attend the clinic after enrollment. you stop your previous oral HIV medication and start the study regimen.

you take lenacapavir 600 mg as an oral tablet. the dose is taken once and will be repeated every 24 weeks (twice a year).

you receive teropavimab 3400 mg and zinlirvimab 3400 mg as intravenous infusions. the infusions are given together during this visit and will be repeated every 24 weeks.

blood is drawn to measure your hiv‑1 viral load (the amount of virus in the blood), cd4+ t‑cell count (a measure of immune health), and baseline safety labs.

2 first safety follow‑up

at week 4 you return to the clinic for a safety check.

you report any side effects or health changes that occurred since the baseline visit.

a blood sample is taken to re‑measure viral load and cd4+ t‑cell count.

3 second safety follow‑up

at week 12 you have another clinic visit.

the same safety assessments are performed: reporting of adverse events and blood draws for viral load and cd4+ t‑cell count.

4 mid‑study visit and drug‑level check

at week 26 you attend a scheduled visit.

blood is drawn to determine trough concentrations of lenacapavir, teropavimab, and zinlirvimab (the lowest level of drug in the blood before the next dose).

viral load, cd4+ t‑cell count, and safety labs are also repeated.

any adverse events are recorded.

5 primary efficacy assessment and second dosing

at week 52 you have a major study visit.

you receive the second dose of lenacapavir 600 mg orally and a second intravenous infusion of teropavimab 3400 mg plus zinlirvimab 3400 mg.

blood is taken to assess hiv‑1 viral load, cd4+ t‑cell count, and trough drug concentrations.

the primary outcome of the study – the proportion of participants with viral load ≥ 50 copies/ml – is evaluated at this point.

all adverse events since the last visit are documented.

6 interim safety visit

at week 68 you return for a safety visit.

you report any new symptoms, and blood is drawn for viral load, cd4+ t‑cell count, and routine safety labs.

7 secondary efficacy assessment

at week 92 you attend a clinic visit for the secondary efficacy assessment.

viral load and cd4+ t‑cell count are measured, and adverse events are recorded.

the study evaluates the proportion of participants with viral load ≥ 50 copies/ml and the proportion with viral load < 50 copies/ml at this time point.

8 final visit and study completion

at week 104 you complete the study.

you receive the third dose of lenacapavir 600 mg orally (if required by the protocol) and the final intravenous infusions of teropavimab 3400 mg and zinlirvimab 3400 mg.

blood is drawn for final viral load, cd4+ t‑cell count, and trough concentrations of all study drugs.

all remaining safety information and adverse events are collected, and the study treatment is discontinued.

Who Can Join the Study?

  • You must be assigned male or female at birth and be 18 years or older.
  • You must be able to understand the study information, sign a written consent form, and follow the study visits and medication schedule.
  • If you were assigned female at birth, can become pregnant, and have heterosexual sex, you must agree to use the birth‑control method required by the study.
  • Your body weight must be at least 35 kilograms (about 77 pounds) at the screening visit.
  • A lab test must show that the HIV virus in your body is sensitive to the two study drugs called TAB and ZAB. This is measured by a special test that looks at how well the drugs work against the virus.
  • Your blood test for HIV (called viral load) must show fewer than 50 copies of the virus per milliliter at screening, which means the virus is undetectable.
  • You need to have at least one viral‑load test done between 6 and 12 months before screening, and all those tests must also show fewer than 50 copies/mL. A single small rise (called a “blip”) up to 400 copies/mL is allowed if the next test is again below 50.
  • You must have a viral‑load test showing fewer than 50 copies/mL within the six months before the earlier test, and if you have more than one test in that period, all must be below 50 copies/mL.
  • You must have been taking a stable oral ART (antiretroviral therapy) regimen for at least six months before screening, and you cannot change that regimen during the screening period.
  • If you could become pregnant, you must have a negative pregnancy test at screening and again on the day you start the study medication.

Who Cannot Join the Study?

  • Having had an opportunistic infection (an infection that occurs when the immune system is weak) or any illness that shows the HIV is in Stage 3.
  • Previously using or being exposed to LEN or a bNAb (a special type of antibody that attacks many forms of HIV) for HIV‑1.
  • Previously using or being exposed to the HIV medicines ibalizumab, fostemsavir, or maraviroc.
  • Being on a treatment plan that includes only one antiretroviral drug (called monotherapy) at the start of the study.
  • Having taken immune‑suppressing medicines (such as corticosteroids, immunoglobulins, or other drugs that lower the immune response) within 4 weeks before screening, unless it was a short course of corticosteroids lasting 7 days or less, or needing ongoing immune‑suppressing treatment during the study.
  • Using any medication that is listed as prohibited for the study, either now or in the past.
  • Being enrolled in, or planning to join, another clinical study without the sponsor’s permission.
  • Previously using or being exposed to long‑acting injectable forms of cabotegravir (LA CAB) or rilpivirine (LA RPV).
  • Currently using or having been exposed to the HIV drugs nevirapine or zidovudine.
  • Testing positive for hepatitis C antibodies and having detectable hepatitis C virus (HCV) RNA, indicating an active hepatitis C infection.
  • Having chronic hepatitis B infection, shown by a positive hepatitis B surface antigen with a negative surface antibody, or a positive core antibody with a negative surface antibody.
  • Being known to have an allergy (hypersensitivity) to the study drug, its breakdown products, or any of its ingredients.
  • Having severe kidney problems, defined as an estimated glomerular filtration rate (eGFR) less than 30 mL/min, which means the kidneys are not filtering blood well.
  • Having an abnormal electrocardiogram (ECG) result that the doctor considers clinically important.
  • Having any of the following lab results at screening:
    ALT (a liver enzyme) more than five times the normal limit;
    direct bilirubin more than 1.5 times the normal limit;
    platelet count less than 50,000 per mm³;
    or hemoglobin less than 8.0 g/dL (a measure of red blood cells).
  • Having other medical or psychiatric conditions, or previous treatments, that the investigator believes could interfere with the study, make it hard to finish study visits, or create too much risk.
  • Being under guardianship, curatorship, or other legal protection that limits the ability to give consent.
  • Having an active, serious infection (other than HIV) that needed treatment within the 30 days before randomization.
  • Having an active tuberculosis (TB) infection.
  • Having acute hepatitis of any cause within the 30 days before randomization.
  • Having a history of, or current, severe liver disease such as decompensated cirrhosis (e.g., fluid buildup in the abdomen, brain changes, or bleeding from enlarged veins) or severe hepatic impairment classified as Child‑Pugh Class C.
  • Having an active cancer that requires immediate systemic (body‑wide) therapy.
  • Having poor vein access that would make it difficult to draw blood or give an IV infusion of the study drugs.
  • Being assigned female at birth and currently pregnant, breastfeeding, planning to become pregnant, or planning to start breastfeeding during the study.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Other Sites

Site Name City Country Status
Azienda Ospedaliero Universitaria Di Modena Modena Italy
National Institute For Infectious Diseases Lazzaro Spallanzani Rome Italy
Ospedale San Raffaele S.r.l. Milan Italy
Wroclawskie Centrum Zdrowia Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wroclaw Poland
Rheinische Friedrich-Wilhelms-Universitaet Bonn Bonn Germany
Hospital Universitario De Canarias La Laguna Spain
Hopital Beaujon Clichy France
Centre Hospitalier Universitaire De Nantes Nantes France
Epfptxv Ubqilpvbverz Mdscvco Cdzlemi Ryznagder (rufqfyo Mbw Rotterdam The Netherlands
Aaoleatyh Ugs Amsterdam The Netherlands
Iosut Oldbsiwo Pepuwoaipen Soa Msdefzg Genoa Italy
Adfvsbd Oqftkwpotre Ugqltyngweepn Fnslsibz Io Di Nyltmr Naples Italy
Uppjlxpdiv Dmalb Sookl Dw Btvsuro Brescia Italy
Ahfp Fkhyhbloipfmzawp Sduyf Milan Italy
Anqiaje Ogrrxvdqofm Pncp Gacidawj Xyyfx Bergamo Italy
Pcbxq Znmtsja Hdbhctbej Jjapgcllhf Lbjyrbz shm pl Gdansk Poland
Woayzwxpne Svmichj Oxhlmzvkefozmbukvfpq Iq Tglcqnma Buprqpls Bydgoszcz Poland
Mgayrgihcx Ollghfken Pcqajd Mannheim Germany
Mlu Mrpwlql Ad Gpgfaqjdkvd Munich Germany
Umwfywewna Hjfurcqo Cnijevt Cologne Germany
Exkzov Gupxtyeywhwm fqhb edkrfwypnogszrxl uyn ksawaysvi Fzvcfdqxw ij duz Myfzybw mvu Berlin Germany
Ixm Snnxl Czucly Gzhe &qyca Cqm Kc Hamburg Germany
Uihgfgnmiozmcccmwoern Enzka Acn Essen Germany
Iry Pdpsmmeznow Goun &bqak Crz Ks Frankfurt Germany
Pkyutw aw Edlljryeat Cologne Germany
Hmkckklz Unkslfohszkww Hajthwzw Ttseo y Prktcr Ijjhrivp Cvgjvk dxswiahfpcqwslycm (zizf Badalona Spain
Hbzxahml Csehlj Dk Bparezfky Barcelona Spain
Fvakzsogb Pfww Lb Itubznlfctdnx Bcemnkihf Dba Helyqytk Uwqjfzlmlzrzd Lp Ppq Madrid Spain
Huhzhhhi Unsvbgcqnfyok 1x Di Ocxsyez Madrid Spain
Hfjsaeoz Cyljjdk Swq Cagvpg Madrid Spain
Hoxodgxg Adhusv Cncwxdsca Vigo Spain
Hueiyawn Uhtcxsstdhtzg Mmdiuut Dm Vtciesilix Santander Spain
Cmrzvn Hjiysspnuku Lgla Swn Pierre Benite France

Want to learn more about this study or check if you can participate? Contact us.

Trial status

Country Status Recruitment Start
France France
Not yet recruiting
01.11.2026
Germany Germany
Not yet recruiting
01.11.2026
Italy Italy
Not yet recruiting
01.11.2026
Poland Poland
Not yet recruiting
01.11.2026
Spain Spain
Not yet recruiting
01.11.2026
The Netherlands The Netherlands
Not yet recruiting
01.11.2026

Trial locations

Lenacapavir is a new type of HIV medicine that blocks the virus’s capsid, a protein shell that protects the virus’s genetic material. In this study it is given as a pill or injection twice a year to see if it can keep the virus suppressed when used with other drugs.

Teropavimab is a broadly neutralizing antibody that is given by IV infusion. It works by attaching to HIV and preventing it from infecting cells. The trial tests whether adding this antibody to the regimen helps maintain viral suppression.

Zinlirvimab is another broadly neutralizing antibody administered by IV infusion. Like teropavimab, it targets HIV directly and blocks the virus from entering cells. The study evaluates its combined effect with lenacapavir and teropavimab.

Cobicistat is a booster medication that increases the levels of other HIV drugs in the body. In the trial participants who stay on their usual oral regimen continue to take cobicistat as part of their combination therapy.

Dolutegravir is an integrase inhibitor that stops HIV from inserting its genetic material into human cells. It is one of the standard drugs used by participants who remain on their usual oral treatment.

Etravirine belongs to a class called non‑nucleoside reverse transcriptase inhibitors (NNRTIs). It blocks an enzyme the virus needs to make copies of its RNA. Participants on the standard regimen may be taking etravirine.

Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) that interferes with the virus’s ability to copy its genetic code. It is a common component of many oral HIV treatment combos in the study.

Raltegravir is another integrase inhibitor that prevents HIV from integrating its DNA into the host’s cells. It is part of the oral regimen for some participants who do not switch to the new antibodies.

Efavirenz is an NNRTI that blocks an enzyme needed for viral replication. It is included in the standard oral therapy for certain participants.

Atazanavir is a protease inhibitor that stops the virus from maturing into a form that can infect new cells. It is used by participants who continue their usual oral regimen.

Rilpivirine is an NNRTI taken orally to inhibit HIV replication. It is part of the existing treatment for some study participants.

Abacavir is an NRTI that interferes with the virus’s ability to make DNA. It is included in the oral treatment options for participants who remain on their current regimen.

Doravirine is an NNRTI that blocks HIV’s reverse transcriptase enzyme. It is one of the drugs participants may continue taking in the standard oral therapy.

Ritonavir is a protease inhibitor that is also used to boost the levels of other HIV drugs. In the study it remains part of the oral regimen for participants who do not switch.

Lamivudine is an NRTI that stops HIV from copying its genetic material. It is commonly combined with other drugs in the standard oral regimen.

Tenofovir alafenamide is a newer form of tenofovir that enters cells and blocks viral replication. It is included in combination pills that participants may continue using.

Elvitegravir is an integrase inhibitor that prevents HIV from integrating its DNA into host cells. It is part of some fixed‑dose combination tablets used by participants staying on oral therapy.

Darunavir is a protease inhibitor that stops HIV from maturing. It is taken by participants who remain on their existing oral regimen.

Tipranavir is a protease inhibitor used in combination with other drugs to control HIV. It is part of the oral treatment options for participants who do not switch to the new regimen.

Tenofovir disoproxil is an older form of tenofovir that blocks HIV replication. It is included in some of the standard oral combination pills used by participants who stay on their usual therapy.

Human immunodeficiency virus infection – It is a viral condition caused by HIV type 1 that enters and multiplies in cells of the immune system. Over time the virus lowers the number of important immune cells, making it harder for the body to fight everyday germs. As the infection continues, the immune protection slowly weakens, which can allow more frequent and longer-lasting infections to appear.

Trial ID:
2025-524336-19-00
Protocol code:
GS-US-536-6544
Trial Phase:
Therapeutic confirmatory (Phase III)

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