Drug Database: 3BNC117

What is 3BNC117?What is 3BNC117?

What is 3BNC117?

3BNC117 is an investigational drug that is being studied as a possible strategy to treat people living with HIV. 3BNC117 belongs to a group of drugs called broadly neutralizing antibodies (bNAbs).²

Long-acting forms of 3BNC117, called 3BNC117-LS (also known as GS-5423 or teropavimab) and 3BNC117-LS-J, are also under study for HIV treatment and/or prevention.^2,4

To learn how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV and AIDS Clinical Trials fact sheets.

How do broadly neutralizing antibodies work?How do broadly neutralizing antibodies work?

How do broadly neutralizing antibodies work?

Antibodies are proteins that the immune system makes to fight infection. A person with HIV produces specific antibodies against HIV. However, most of these antibodies do not stop HIV from multiplying in the body.^5,6

Some people with HIV naturally produce rare types of HIV antibodies called broadly neutralizing antibodies (bNAbs). bNAbs are powerful antibodies that can work against different HIV strains. bNAbs can block HIV from entering healthy cells and activate other immune cells to help destroy infected cells.^6–8

Researchers are investigating whether giving bNAbs to people with HIV can help them maintain undetectable levels of HIV without the need for daily antiretroviral therapy. Additionally, some bNAbs are being studied because they may be able to reduce the size of the latent HIV reservoir.^7,9

Researchers are also trying to find out if 3BNC117 can prevent HIV infection in people who do not have the virus.⁴ This record focuses on the study of 3BNC117 as a treatment for HIV.

Select clinical trials of 3BNC117Select clinical trials of 3BNC117

Select clinical trials of 3BNC117

Study Name: NCT02588586

Phase: 2
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate the safety of 3BNC117 and its ability to delay or prevent viral rebound during an analytical treatment interruption of ART.¹⁰

Study Name: NCT02446847

Phase: 2a
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate the safety and drug properties of 3BNC117. The study also examined how well 3BNC117 could delay or prevent viral rebound during an analytical treatment interruption of ART.¹¹ 
Selected Study Results: Results published in Nature (2016) showed that 3BNC117 was safe and well tolerated. 3BNC117 was effective in delaying viral rebound following an analytical treatment interruption of ART.¹²

Study Names: ROADMAP; NCT02850016

Phase: 2a
Status: This study has been completed.
Locations: Denmark, Germany, United States
Purpose: The purpose of this study was to compare the efficacy of the latency reversing agent romidepsin plus 3BNC117 to the efficacy of romidepsin alone on delaying or preventing viral rebound during an analytical treatment interruption of ART.^13,14 
Selected Study Results: Results published in The Lancet Microbe (2022) showed that romidepsin plus 3BNC117 and romidepsin given alone had no substantial effect on reducing latent HIV reservoir size in participants with viral suppression on ART. Additionally, romidepsin plus 3BNC117, compared to romidepsin given alone, was not effective in delaying the time to viral rebound during analytical treatment interruption. The observed time to viral rebound was not clinically meaningful in either group.¹⁴

Study Names: eCLEAR; NCT03041012

Phase: 1b/2a
Status: This study has been completed.
Locations: Denmark and United Kingdom
Purpose: The purpose of this study was to evaluate whether the early administration of romidepsin and/or 3BNC117 in treatment-naive individuals who were starting ART could reduce the time to viral suppression, limit the size of the latent HIV reservoir, and delay the time to viral rebound during an analytical treatment interruption of ART.^2,15
Selected Study Results: Results presented at CROI 2022 and published in Nature Medicine (2022) showed that the early administration of 3BNC117, with or without romidepsin, led to faster viral load decline and significantly enhanced the elimination of infected cells after ART initiation, as compared to what was observed in participants receiving ART only. After 1 year, latent HIV reservoir size was reduced from baseline in all treatment groups, with the greatest reduction seen in people receiving 3BNC117 plus ART. Among participants who received 3BNC117 and had 3BNC117-sensitive virus, 80% maintained viral control during treatment interruption of ART. In contrast, among participants who had 3BNC117-resistant virus or did not receive 3BNC117, only 20% maintained viral control during treatment interruption.^16,17

Study Names: TITAN; NCT03837756

Phase: 2a
Status: This study has been completed.
Locations: Australia, Denmark, Norway, United States
Purpose: The purpose of this study was to evaluate the safety and effectiveness of lefitolimod and the bNAbs 3BNC117 and 10-1074 in delaying the time to viral rebound during an analytical treatment interruption of ART.¹⁸
Selected Study Results: Results published in Nature Medicine (2023) and presented at CROI 2023 showed that the groups receiving dual bNAb treatment had a significant delay in the time to viral rebound during an analytical treatment interruption of ART, as compared to groups receiving placebos only or lefitolimod plus placebo. The addition of lefitolimod to dual bNAb treatment did not confer any additional effect on viral control compared to dual bNAb treatment alone.^19,20

Study Name: NCT03719664

Phase: 2
Status: The status of this study is unknown.
Location: United States
Purpose: The purpose of this study is to determine the most effective dose of 3BNC117 and the investigational fusion inhibitor albuvirtide and evaluate the safety and effectiveness of this combination as long-acting maintenance treatment.²¹

Study Names: RIO; NCT04319367

Phase: 2
Status: This study is currently recruiting participants.
Location: United Kingdom
Purpose: The purpose of this study is to determine whether the combination of the two long-acting bNAbs 3BNC117-LS and 10-1074-LS can prevent viral rebound during an analytical treatment interruption of ART.²²

Study Name: NCT04819347

Phase: 2
Status: The status of this study is unknown.
Location: China
Purpose: The purpose of this study is to evaluate the safety of combination therapy with albuvirtide plus 3BNC117 and assess whether this combination can control viral load levels during an analytical treatment interruption of ART.²³

Study Name: NCT04560569

Phase: 2
Status: The status of this study is unknown.
Location: United States
Purpose: The purpose of this study is to evaluate the safety and efficacy of combination therapy with albuvirtide plus 3BNC117 in people who have multidrug-resistant HIV.²⁴

Study Names: RHIVIERA-02; NCT05300035

Phase: 2
Status: See the ClinicalTrials.gov record for this study’s status.
Location: France
Purpose: The purpose of this study is to evaluate whether the administration of the long-acting bNAbs 3BNC117-LS and 10-1074-LS in people with primary HIV infection who are initiating ART can control viral load levels during an analytical treatment interruption of ART.²⁵

Study Names: A5374; NCT06071767

Phase: 1/2a
Status: See the ClinicalTrials.gov record for this study’s status.
Location: United States and Brazil
Purpose: The purpose of this study is the evaluate the safety and efficacy of a combination regimen in adults who initiated suppressive ART during acute HIV infection. The combination regimen includes therapeutic HIV vaccines, the immune modulator vesatolimod, and two bNAbs (3BNC117-LS and 10-1074-LS).²⁶

Study Names: GS-US-536-5939; NCT05729568

Phase: 2
Status: This study is currently recruiting participants.
Location: United States, Australia, Canada, and Puerto Rico
Purpose: The purpose of this study is to evaluate the safety and efficacy of the bNAbs 3BNC117-LS (also known as GS-5423) and 10-1074-LS (also known as GS-2872) in combination with the capsid inhibitor lenacapavir as long-acting treatment.²⁷

For more details on the studies listed above, see the Health Professional version of this drug summary.

Additional studies evaluating 3BNC117 for HIV treatment have been or are being conducted, including the following early-phase trials:

• NCT03526848: A Phase 1b study that assessed whether 3BNC117 and 10-1074 could prevent viral rebound in adults with HIV during an analytical treatment interruption of ART. This study has been completed and results are available from Nature (2022).²⁸
• NCT04250636: A Phase 1 study that evaluated the safety, pharmacokinetics, and antiviral activity of single infusions of both 3BNC117-LS and 10-1074-LS in adults with HIV who were off ART. This study has been completed and results are available from CROI 2022.²⁹
• BEAT-2 (NCT03588715): A Phase 1 study that evaluated whether the immune modulator peginterferon alfa-2b plus 3BNC117 and 10-1074 could control viral rebound and reduce the latent HIV reservoir in adults with HIV during an analytical treatment interruption of ART. This study has been completed, and main outcome results are available from CROI 2023.^2,30 
• NCT04811040: A Phase 1b study that evaluated the safety and efficacy of 3BNC117-LS and 10-1074-LS in combination with the capsid inhibitor lenacapavir in controlling viral load levels in adults with HIV and viral suppression on ART. This study has been completed. Results were presented at CROI 2023.³¹
• MCA-1031 (ES38918) (NCT05245292): A Phase 1 trial evaluating the safety and antiviral activity of 3BNC117-LS and 10-1074-LS in combination with N-803 (an investigational therapy based on the cytokine IL-15) in virologically suppressed adults with HIV during an analytical treatment interruption of ART. This study is currently recruiting participants.³²
• NCT05612178: A Phase 1 study investigating the safety and efficacy of 3BCNC117-LS and 10-1074-LS on persistent viral reservoirs in people with HIV on suppressive ART. This study is currently recruiting participants.³³
• ACTG A5416 (NCT06031272): A Phase 1 study evaluating the safety and antiviral activity of 3BNC117-LS-J and 10-1074-LS-J in virologically suppressed adults with HIV undergoing an ATI of ART.  See the ClinicalTrials.gov record for this study’s status.³⁴

What side effects might 3BNC117 cause?What side effects might 3BNC117 cause?

What side effects might 3BNC117 cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of 3BNC117 listed above. 

NCT02446847

In this study looking at multiple infusions of 3BNC117 in 13 participants, most side effects were temporary and mild. Some participants experienced modest drops in their CD4 counts during the study, but most had their counts return to baseline levels by Week 12.¹²

ROADMAP (NCT02850016)

In the ROADMAP trial, 11 participants received romidepsin plus 3BNC117 and nine participants received romidepsin alone. All participants in both groups experienced side effects, most of which were mild to moderate in severity. More drug-related side effects occurred with romidepsin than with 3BNC117.¹⁴

eCLEAR (NCT03041012)

In the eCLEAR study, treatment-naive participants received ART only; ART plus 3BNC117; ART plus romidepsin; or a combination of ART, 3BNC117, and romidepsin. In total, 319 side effects occurred during the trial. Twenty-nine side effects, most of which were mild, were related to 3BNC117. The most common 3BNC117-related side effects were fatigue and headache.¹⁷

TITAN (NCT03837756)

In this Phase 2a trial, participants were randomly assigned to receive placebo/placebo, lefitolimod/placebo, placebo/bNAbs, or lefitolimod/bNAbs. In total, 253 side effects were reported during the trial. Fourteen side effects were related to bNAb therapy — 11 were mild, two were moderate, and one was severe. The severe bNAb-related side effect was an infusion-related reaction to 3BNC117 that resolved with treatment. The most common side effect related to bNAb therapy was fatigue.¹⁹

Because 3BNC117 is still being studied, information on possible side effects of the drug is not complete. As testing of 3BNC117 continues, additional information on possible side effects will be gathered.
 

Where can I get more information about clinical trials studying 3BNC117?Where can I get more information about clinical trials studying 3BNC117?

Where can I get more information about clinical trials studying 3BNC117?

More information about 3BNC117-related research studies is available from ClinicalTrials.gov. (The ClinicalTrials.gov search can be modified so that you can get results that better match your interests.)

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

ReferencesReferences

References

1. National Center for Biotechnology Information. PubChem substance record for SID 381127297, 3BNC117, Source: ChemIDplus. Accessed December 18, 2023
2. Treatment Action Group website. Research toward a cure trials. Accessed December 18, 2023
3. Gilead Sciences: press release, dated January 9, 2020. Gilead Sciences licenses portfolio of HIV antibodies from The Rockefeller University. Accessed December 18, 2023
4. Jefferys R. HIV vaccines & passive immunization. Treatment Action Group Pipeline Report 2023. Accessed December 18, 2023
5. Snow B. The rise of broadly neutralizing antibodies. AIDS Vaccine Advocacy Coalition (AVAC). Published May 17, 2018. Accessed December 18, 2023
6. HIV Vaccine Trials Network (HVTN). Using antibodies for HIV prevention. Accessed December 18, 2023
7. National Institute of Allergy and Infectious Diseases (NIAID). Sustained ART-free HIV remission. Accessed December 18, 2023
8. National Institute of Allergy and Infectious Diseases (NIAID). Future directions for HIV treatment research. Accessed December 18, 2023
9. Grobben M, Stuart RA, van Gils MJ. The potential of engineered antibodies for HIV-1 therapy and cure. Current Opinion in Virology. 2019;38:70-80. doi:10.1016/j.coviro.2019.07.007. Accessed December 18, 2023
10. Rockefeller University. An open label, Phase 2 study of the safety and antiretroviral activity of 3BNC117 in HIV-infected individuals on combination antiretroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 26, 2015. NLM Identifier: NCT02588586. Accessed December 18, 2023
11. Rockefeller University. A Phase 2, open label study of the safety, antiretroviral activity and pharmacokinetics of 3BNC117 during a short analytical treatment interruption in HIV-infected subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 17, 2015. NLM Identifier: NCT02446847. Accessed December 18, 2023 
12. Scheid JF, Horwitz JA, Bar-On Y, et al. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature. 2016;535(7613):556-560. Accessed December 18, 2023
13. Rockefeller University. A Phase 2a, randomized study of romidepsin with or without 3BNC117 to evaluate the effects on the HIV-1 reservoir (ROADMAP). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 26, 2016. NLM Identifier: NCT02850016. Accessed December 18, 2023
14. Gruell H, Gunst JD, Cohen YZ, et al. Effect of 3BNC117 and romidepsin on the HIV-1 reservoir in people taking suppressive antiretroviral therapy (ROADMAP): a randomised, open-label, phase 2A trial. The Lancet Microbe. 2022;3(3):e203-e214. doi:10.1016/S2666-5247(21)00239-1. Accessed December 18, 2023
15. Aarhus University Hospital. Early administration of latency reversing therapy and broadly neutralizing antibodies to limit the establishment of the HIV-1 reservoir during initiation of antiretroviral treatment - a randomized controlled trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 20, 2017. NLM Identifier: NCT03041012. Accessed December 18, 2023
16. Gunst JD, Pahus MH, Rosás-Umbert M, et al. The impact of 3BNC117 and romidepsin treatment at ART initiation on HIV-1 persistence. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 12-16, 2022; Virtual. Accessed December 18, 2023
17. Gunst JD, Pahus MH, Rosás-Umbert M, et al. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial. Nat Med. 2022;28(11):2424-2435. doi:10.1038/s41591-022-02023-7. Accessed December 18, 2023
18. University of Aarhus. Combining a TLR9 agonist with broadly neutralizing antibodies for reservoir reduction and immunological control of HIV infection: an investigator-initiated randomized, placebo-controlled, Phase IIa trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 7, 2019. NLM Identifier: NCT03837756. Accessed December 18, 2023
19. Gunst JD, Højen JF, Pahus MH, et al. Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial. Nat Med. 2023;29(10):2547-2558. doi:10.1038/s41591-023-02547-6. Accessed December 18, 2023
20. Gunst JD, Reikvam DH, McMahon JH, et al. The impact of 3BNC117, 10-1074, and lefitolimod on HIV-1 persistence: the TITAN trial. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 19-22, 2023; Seattle, WA. Abstract 136. Accessed December 18, 2023
21. Frontier Biotechnologies Inc. A Phase 2, multicenter, three-part study to establish the dosage, safety and antiviral activity of combination therapy with albuvirtide and 3BNC117 as long-acting maintenance therapy in virologically suppressed subjects with HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 22, 2018. NLM Identifier: NCT03719664. Accessed December 18, 2023
22. Imperial College London. A randomised placebo controlled trial of ART plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) vs ART plus placebo in treated primary HIV infection on viral control off ART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 2, 2020. NLM Identifier: NCT04319367. Accessed December 18, 2023
23. Frontier Biotechnologies Inc. The Phase 2, two arms, one site, safety and antiviral activity of combination therapy with albuvirtide and 3BNC117 in virologically suppressed subjects with HIV-1 infection after analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 22, 2021. NLM Identifier: NCT04819347. Accessed December 18, 2023
24. Frontier Biotechnologies Inc. A multicenter, two-arm, 24-week study of albuvirtide in combination with 3BNC117 in patients with multi-drug resistant (MDR) HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 17, 2020. NLM Identifier: NCT04560569. Accessed December 18, 2023
25. ANRS, Emerging Infectious Diseases. A randomised Phase II placebo-controlled trial of antiretroviral therapy (ART) plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) vs ART plus placebo during primary HIV-1 infection to study the impact on post-treatment HIV control. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US).  Registered on January 3, 2022. NLM Identifier: NCT05300035. Accessed December 18, 2023
26. National Institute of Allergy and Infectious Diseases (NIAID). A Phase I/IIa randomized, placebo-controlled trial of conserved-mosaic T-cell vaccine in a regimen with vesatolimod and broadly neutralizing antibodies in adults initiated on suppressive antiretroviral therapy during acute HIV-1. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 5, 2023. NLM Identifier: NCT06071767. Accessed December 18, 2023
27. Gilead Sciences. A Phase 2 randomized, open-label study to evaluate the safety and efficacy of broadly neutralizing antibodies (bNAbs) GS-5423 and GS-2872 in combination with the capsid inhibitor lenacapavir as long-acting treatment dosed every 6 months in virologically suppressed adults with HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 6, 2023. NLM Identifier: NCT05729568. Accessed December 18, 2023
28. Rockefeller University. An open label, randomized study of the safety and antiretroviral activity of 3BNC117 and 10-1074 in HIV-infected individuals on combination antiretroviral therapy and during analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 3, 2018. NLM Identifier: NCT03526848. Accessed December 18, 2023
29. Rockefeller University. An open label, single arm study of the safety, pharmacokinetics and antiretroviral activity of the combination of 3BNC117-LS and 10-1074-LS in viremic HIV-infected individuals. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 30, 2020. NLM Identifier: NCT04250636. Accessed December 18, 2023
30. Luis Montaner. Pilot study on innate activation and viral control in HIV-infected adults undergoing an analytical treatment interruption after administration of pegylated interferon alpha 2b with broadly HIV-1 neutralizing antibodies (3BNC117, 10-1074). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 30, 2018. NLM Identifier: NCT03588715. Accessed December 18, 2023
31. Gilead Sciences. A Phase 1b randomized, blinded, proof-of-concept study to evaluate the safety and efficacy of broadly neutralizing antibodies (bNAbs) GS-5423 and GS-2872 in combination with capsid inhibitor lenacapavir (GS-6207) in virologically suppressed adults with HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 19, 2021. NLM Identifier: NCT04811040. Accessed December 18, 2023
32. Rockefeller University. An open label, single arm study of the safety and antiretroviral activity of two long-acting broadly neutralizing antibodies plus an IL-15 superagonist in ART-treated adults living with HIV during analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 8, 2022. NLM Identifier: NCT05245292. Accessed December 18, 2023
33. National Institute of Allergy and Infectious Diseases (NIAID). A randomized placebo-controlled study to evaluate the safety and effects of repeated doses of 3BNC117-LS and 10-1074-LS on persistent viral reservoirs in people living with HIV and on suppressive antiretroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 9, 2022. NLM Identifier: NCT05612178. Accessed December 18, 2023
34. AIDS Clinical Trials Group. A Phase I, randomized, placebo-controlled study of the safety, antiviral & immunomodulatory activity of broadly neutralizing antibodies 3BNC117-LS-J and 10-1074-LS-J in combination in ART-treated adults in sub-Saharan Africa living with HIV during a monitored analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 14, 2023. NLM Identifier: NCT06031272. Accessed December 18, 2023