Drug Database: 10-1074

What is 10-1074?What is 10-1074?

What is 10-1074?

10-1074 is an investigational drug that is being studied as a possible strategy to treat people living with HIV. 10-1074 belongs to a group of drugs called broadly neutralizing antibodies (bNAbs).¹

Long-acting forms of 10-1074, called 10-1074-LS (also known as GS-2872 or zinlirvimab) and 10-1074-LS-J, are also under study for HIV treatment and/or prevention.^1,2

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.^4,5

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.^4,6,7

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.^6,8

Researchers are also trying to find out if 10-1074 can prevent HIV infection in people who do not have the virus.² This record focuses on the study of 10-1074 as a treatment for HIV.

Select clinical trials of 10-1074Select clinical trials of 10-1074

Select clinical trials of 10-1074

Study Names: Tatelo Study; NCT03707977

Phase: 1/2
Status: This study has been completed.
Location: Botswana
Purpose: The purpose of this study was to evaluate the efficacy of 10-1074 and another investigational bNAb called VRC01LS in maintaining viral suppression in a group of children who had received early antiretroviral therapy (ART).⁹
Selected Study Results: Results published in Sci Transl Med (2023) and presented at CROI 2022 showed that treatment with both 10-1074 and VRC01LS was safe and effective. Among the study participants who stopped ART, 44% maintained viral load levels of less than 40 copies/mL through 24 weeks of bNAb-only treatment. Participants with a longer time on ART and bNAb overlap were more likely to succeed along with participants who enrolled earlier in the study and had favorable pre-intervention clinical and reservoir characteristics.^10,11

Additional Published Material:

• CROI, 2020: Safety and pharmacokinetics of intravenous VRC01LS and 10-1074 in young children
• CROI, 2021: Safety and pharmacokinetics of VRC01LS and 10-1074 among children in Botswana

Study Name: NCT04357821

Phase: 1/2
Status: This study is ongoing, but not recruiting participants.
Location: United States
Purpose: The purpose of this study is to evaluate whether a combination regimen consisting of therapeutic HIV vaccines, the bNAbs VRC07-523LS plus 10-1074, and lefitolimod can control viral load levels during an analytical treatment interruption of ART.¹²
Selected Study Results: Results presented at CROI 2023 indicated that most of the participants (seven out of 10) who received combination therapy had at least partial virologic control after an analytical treatment interruption of ART. The average time to viral rebound following ART interruption was 15 weeks.¹³

Study Names: A5374; NCT06071767

Phase: 1/2a
Status: This study is currently recruiting participants.
Locations: 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 contains therapeutic HIV vaccines, the immune modulator vesatolimod, and the long-acting bNAbs 3BNC117-LS (also known as GS-5423) and 10-1074-LS (also known as GS-2872).¹⁴

Study Names: TITAN; NCT03837756

Phase: 2a
Status: This study has been completed.
Locations: United States, Australia, Denmark, and Norway
Purpose: The purpose of this study was to evaluate the safety and efficacy of lefitolimod plus the bNAbs 3BNC117 and 10-1074 in delaying the time to viral rebound during an analytical treatment interruption of ART.¹⁵
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.^16,17

Study Names: RIO; NCT04319367

Phase: 2
Status: This study is currently recruiting participants.
Locations: Denmark and United Kingdom
Purpose: The purpose of this study is to determine whether the combination of two long-acting bNAbs, 3BNC117-LS and 10-1074-LS, can prevent viral rebound during an analytical treatment interruption of ART.^18,19

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

Phase: 2
Status: This study is ongoing, but not recruiting participants.
Locations: 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.²⁰

Study Names: RHIVIERA-02; NCT05300035

Phase: 2
Status: This study is currently recruiting participants.
Location: France
Purpose: The purpose of this study is to evaluate the efficacy of the long-acting bNAbs 3BNC117-LS and 10-1074-LS in controlling viral load levels during an analytical treatment interruption of ART.²¹

Study Names: ACACIA Study; ACTG A5417; NCT06205602

Phase: 2
Status: See the ClinicalTrials.gov record for this study’s status.
Location: Sub-Saharan Africa
Purpose: The purpose of this study is to evaluate the safety of the long-acting bNAbs 3BNC117-LS and 10-1074-LS and determine whether the combination of the two bNAbs can prevent viral rebound during an analytical treatment interruption of ART.²²

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

Additional studies evaluating 10-1074 for HIV treatment have been completed or are being conducted, including the following early-phase trials:

• NCT03526848: A Phase 1 study that evaluated whether 3BNC117 and 10-1074 could control viral load levels in adults with HIV during an analytical treatment interruption of ART. This study has been completed and results are available from Nature (2022).²³
• 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 2022.²⁴
• NCT04811040: A Phase 1b study that evaluated the safety and efficacy of 3BNC117-LS (also known as GS-5423) and 10-1074-LS (also known as GS-2872) in combination with the capsid inhibitor lenacapavir in controlling viral load levels in adults with viral suppression. This study has been completed and results are available from The Lancet HIV (2024) and CROI 2024.²⁵
• 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.^1,26
• ACTG A5386 (NCT04340596): A Phase 1 trial evaluating the safety and efficacy of N-803 (an investigational therapy based on the cytokine IL-15) administered with and without the bNAbs VRC07-523LS and 10-1074 in controlling viral load during an analytical treatment interruption of ART. This study is currently recruiting participants.²⁷
• 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 in virologically suppressed adults with HIV during an analytical treatment interruption of ART. This study is ongoing, but not recruiting participants.²⁸
• 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.²⁹
• ACTG A5416 (NCT06031272): A Phase 1 study evaluating the safety and antiviral activity of 3BNC117-LS-J and 10-1074-LS-J in adults with viral suppression undergoing an analytical treatment interruption of ART. This study is currently recruiting participants.³⁰

What side effects might 10-1074 cause?What side effects might 10-1074 cause?

What side effects might 10-1074 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 10-1074 listed above. 

Tatelo Study (NCT03707977)

In this Phase 1/2 trial, 28 children received daily ART plus the bNAbs VRC01LS and 10-1074 given once every 4 weeks for at least 8 weeks. Thereafter, 25 of the 28 children stopped ART and continued dual bNAb therapy for up to 24 weeks. No infusion reactions were reported throughout the study. Five severe side effects occurred in three participants. One of the severe side effects (neutropenia) was possibly related to bNAb treatment. No life-threatening side effects occurred during the study, and no participants discontinued study treatment because of severe side effects.^9,11

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.¹⁶

Because 10-1074 is still being studied, information on possible side effects of the drug is not complete. As testing of 10-1074 continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying 10-1074?Where can I get more information about clinical trials studying 10-1074?

Where can I get more information about clinical trials studying 10-1074?

More information about 10-1074-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. Treatment Action Group website. Research toward a cure trials. Accessed October 24, 2024
2. Jefferys R. The HIV vaccines and passive immunization pipeline report 2024. Treatment Action Group Pipeline Report 2024. Accessed October 24, 2024
3. Gilead Sciences: press release, dated January 9, 2020. Gilead Sciences licenses portfolio of HIV antibodies from The Rockefeller University. Accessed October 24, 2024
4. HIV Vaccine Trials Network (HVTN). Using antibodies for HIV prevention. Accessed October 24, 2024
5. Snow B. The rise of broadly neutralizing antibodies. AIDS Vaccine Advocacy Coalition (AVAC). Published May 17, 2018. Accessed October 24, 2024
6. National Institute of Allergy and Infectious Diseases (NIAID). Sustained ART-free HIV remission. Accessed October 24, 2024
7. National Institute of Allergy and Infectious Diseases (NIAID). Future directions for HIV treatment research. Accessed October 24, 2024
8. 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 October 24, 2024
9. National Institute of Allergy and Infectious Diseases (NIAID). A clinical trial to evaluate the impact of broadly neutralizing antibodies VRC01LS and 10-1074 on maintenance of HIV suppression in a cohort of early-treated children in Botswana (dual bNAb treatment in children). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 12, 2018. NLM Identifier: NCT03707977. Accessed October 24, 2024
10. Shapiro RL, Maswabi K, Ajibola G, et al. Treatment with broadly neutralizing antibodies in children with HIV in Botswana (The Tatelo Study). Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 12-16, 2022; Virtual. Accessed October 24, 2024
11. Shapiro RL, Ajibola G, Maswabi K, et al. Broadly neutralizing antibody treatment maintained HIV suppression in children with favorable reservoir characteristics in Botswana. Science Translational Medicine. 2023;15(703):eadh0004. doi:10.1126/scitranslmed.adh0004. Accessed October 24, 2024
12. University of California, San Francisco. Combinatorial therapy with a therapeutic conserved element DNA vaccine, MVA vaccine boost, TLR9 agonist and broadly neutralizing antibodies: a proof-of-concept study aimed at inducing an HIV remission. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 18, 2020. NLM Identifier: NCT04357821. Accessed October 24, 2024
13. Peluso M, Deitchman A, Magombedze G, et al. Rebound dynamics following immunotherapy with an HIV vaccine, TLR-9 agonist, and broadly neutralizing antibodies. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 19-22, 2023; Seattle, WA. Poster 435. Accessed October 24, 2024
14. 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 October 24, 2024
15. 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 October 24, 2024
16. 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 October 24, 2024
17. 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 October 24, 2024
18. 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 October 24, 2024
19. Lee JM, Collins S, Babalis D, et al. The RIO trial: rationale, design, and the role of community involvement in a randomised placebo-controlled trial of antiretroviral therapy plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) in participants diagnosed with recent HIV infection—study protocol for a two-stage randomised phase II trial. Trials. 23(1):263. doi:10.1186/s13063-022-06151-w. Accessed October 24, 2024
20. 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 October 24, 2024
21. 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 October 24, 2024
22. Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections. A randomized, double-blind, placebo-controlled study of the combination of two long-acting broadly neutralizing antibodies at ART initiation in adults living with HIV-1 in Sub-Saharan Africa: The ACACIA Study. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 4, 2024. NLM Identifier: NCT06205602. Accessed October 24, 2024
23. 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 October 24, 2024
24. 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 October 24, 2024
25. 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 October 24, 2024
26. 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 October 24, 2024
27. National Institute of Allergy and Infectious Diseases (NIAID). A Phase I clinical trial of the safety, tolerability, and efficacy of IL-15 superagonist (N-803) with and without combination broadly neutralizing antibodies to induce HIV-1 control during analytic treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 23, 2020. NLM Identifier: NCT04340596. Accessed October 24, 2024
28. 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 October 24, 2024
29. 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 October 24, 2024
30. 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 October 24, 2024