Drug Database: VRC07-523LS

What is VRC07-523LS? What is VRC07-523LS?

What is VRC07-523LS?

VRC07-523LS is an investigational drug that is being studied as a possible strategy to treat people with HIV. VRC07-523LS belongs to a group of drugs called broadly neutralizing antibodies (bNAbs).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.^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.^5,7,8

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 (ART). 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 VRC07-523LS can prevent HIV in people who do not have the virus.^3,4 This record focuses on the study of VRC07-523LS as a treatment for HIV.

Select clinical trials of VRC07-523LS Select clinical trials of VRC07-523LS

Select clinical trials of VRC07-523LS

Study Names: IAVI T003; NCT03721510

Phase: 1/2a
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of the bNAbs PGT121, VRC07-523LS, and PGDM1400 in adults with and without HIV.¹⁰
Selected Study Results: Results published in Nature Medicine (2024) and presented at CROI 2024 showed that triple bNAb therapy with PGT121, VRC07-523LS, and PGDM1400 was generally safe and well tolerated. Most participants (83%) who received bNAb therapy while undergoing an analytical treatment interruption of antiretroviral therapy (ART) maintained viral suppression for at least 28 weeks. Although bNAb concentrations declined to low or undetectable levels during the follow-up period, 42% of the participants had viral suppression for at least 38 to 44 weeks.^11,12

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 of (1) therapeutic HIV vaccines, (2) bNAbs VRC07-523LS and 10-1074, and (3) the latency-reversing agent lefitolimod can control viral load levels in participants undergoing an analytical treatment interruption of ART.^13,14
Selected Study Results: Results presented at CROI 2023 indicated that most participants (seven out of 10) who received combination therapy had a least partial virologic control after ART interruption. The average time to viral rebound following ART interruption was 15 weeks.¹⁴

Study Name: NCT04983030

Phase: 1/2a
Status: This study is ongoing, but not recruiting participants.
Location: United States
Purpose: The purpose of this study is to evaluate the safety, immunogenicity, and efficacy of therapeutic HIV vaccines in combination with the bNAbs PGT121, PGDM1400, ad VRC07-523LS in adults with viral suppression on ART. Researchers will assess whether this combination strategy can control participants’ viral load levels during an analytical treatment interruption of ART.¹⁵

Study Name: NCT05275998

Phase: 1b/2a
Status: This study has been completed.
Location: United States
Purpose: The purpose of this dose-escalation trial was to evaluate the safety, pharmacokinetics, and antiviral activity of the bNAbs TMB-365 and TMB-380 (also known as VRC07-523LS) in individuals with viral suppression on ART.¹⁶
Selected Study Results: Results presented at CROI 2025 showed that a single intravenous (IV) infusion of TMB-365 and TMB-380 given every 8 weeks in participants undergoing an analytical treatment interruption of ART was effective in maintaining viral suppression in most participants (94%) throughout the 24-week treatment period. The TMB-365 and TMB-380 bNAb combination was generally safe with no serious or severe side effects reported.¹⁷
Additional Published Material:

• CROI 2024: A dose escalation study of safety & PK of TMB-365 & TMB-380 in people with suppressed HIV

Study Names: ACTG A5357; NCT03739996

Phase: 2
Status: This study has been completed.
Locations: United States and Puerto Rico
Purpose: The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of long-acting cabotegravir (CAB LA) plus VRC07-523LS in adults with viral suppression.¹⁸
Selected Study Results: Results published in Clinical Infectious Diseases (2025) and presented at CROI 2024 demonstrated that CAB LA plus VRC07-523LS was safe and capable of maintaining viral suppression in most of the participants. Eleven participants had severe side effects (mostly temporary infusion reactions) that were at least possibly related to CAB LA or VRC07-523LS, and one participant discontinued treatment due to a mild infusion-related reaction. Five out of 71 participants experienced virologic failure during treatment with CAB LA plus VRC07-523LS.^19,20

Study Names: GS-US-382-5445; NCT05281510

Phase: 2a
Status: This study has been completed.
Location: South Africa
Purpose: The purpose of this trial was to evaluate the safety and tolerability of the bNAbs VRC07-523LS and CAP256V2LS in combination with the immune modulator vesatolimod in early ART-treated women with clade C HIV.²¹
Selected Study Results: Results presented at CROI 2025 showed that vesatolimod and the bNAbs VRC07-523LS and CAP256V2LS were safe, with no treatment-related serious side effects reported. Most of the participants (90%) experienced infusion-related reactions, all of which were mild to moderate in severity and went away within 2 days. One participant discontinued vesatolimod because of a side effect. During an analytical treatment interruption of ART, varying patterns of viral control were seen among the 20 participants.²²
Additional Published Material:

• IAS, 2025: Vesatolimod pharmacodynamic responses in a trial of vesatolimod and broadly neutralizing antibodies in early-treated South African women with clade C HIV-1

Study Names: A5388; NCT05719441

Phase: 2
Status: See the ClinicalTrials.gov record for this study's status.
Locations: United States, Brazil, Peru
Purpose: The purpose of this study is to determine whether administration of the bNAbs VRC07-523LS and PGT121.414.LS in adults who are initiating ART during acute HIV infection is safe and to determine whether this combination strategy can induce HIV remission.²³

Study Names: IMPAACT 2042; Tatelo Plus Study; NCT06508749

Phase: 1/2
Status: This study is currently recruiting participants.
Location: Botswana
Purpose: The purpose of this study is to evaluate the impact of three bNAbs (PGDM1400LS, VRC07-523LS, and PGT121.414.LS) or analytical treatment interruption on the viral reservoir, immune function, and maintenance of HIV suppression in children in Botswana who had started ART early in life.²⁴

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

Additional studies evaluating VRC07-523LS for HIV treatment have been completed or are being conducted, including the following Phase 1 trials:

• VOR-07 study (NCT03803605): A trial that evaluated the effects of the latency-reversing agent vorinostat plus VRC07-523LS on persistent HIV infection. This study has been completed, and results are available from IAS 2021 and The Journal of Infectious Diseases (2021).²⁵
• VRC 607/ACTG A5378 (NCT02840474): A trial that evaluated the safety and antiviral effects of the bNAbs VRC01LS and VRC07-523LS in treatment-naive adults with HIV. This study has been completed, and results are available from IAS 2019 and the Journal of Clinical Investigation Insight (2025).²⁶
• IAVI T002 (NCT03205917): A study that evaluated the safety, tolerability, pharmacokinetics, and antiviral activity of the bNAbs PGDM1400, PGT121, and VRC07-523LS in adults without HIV and adults with HIV who were not on ART. This study has been completed, and results are available from CROI 2022 and Nature Medicine (2022).²⁷
• ACTG A5386 (NCT04340596): A trial investigating 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 ongoing, but not recruiting participants.²⁸
• RV 630/DELIVER-01 (NCT06484335): A trial evaluating the safety and efficacy of the bNAbs VRC07-523LS and PGDM1400LS in combination with therapeutic HIV vaccines for the induction of HIV remission in adults with HIV who initiated or will initiate ART during acute HIV infection. See the ClinicalTrials.gov record for this study’s status.²⁹
• PACTR202309578224660: A study assessing whether the bNAbs CAP256V2LS and VRC07-523LS can control viral load in participants who undergo an analytical treatment interruption of ART. See the Pan African Clinical Trials Registry record for this study’s status.³⁰
• A5389 (NCT06987318): A study evaluating the effectiveness of VRC07-523LS and PGT121.414.LS in controlling viral load levels during an analytical treatment interruption of ART in adults with HIV who had initiated ART during acute HIV infection. See the ClinicalTrials.gov record for this study’s status.³¹

What side effects might VRC07-523LS cause? What side effects might VRC07-523LS cause?

What side effects might VRC07-523LS 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 VRC07-523LS listed above.

IAVI T003 (NCT03721510)

In this Phase 1/2a trial evaluating PGT121, VRC07-523LS, and PGDM1400, all three bNAbs studied were reported to be generally safe and well tolerated. There were four serious side effects, all of which were unrelated to the study bNAbs.^10,11

NCT04357821

In this Phase 1/2 trial, 10 participants received a combination regimen consisting of therapeutic HIV vaccinations, bNAbs VRC07-523LS and 10-1074, and the latency-reversing agent lefitolimod. Two participants experienced severe alanine aminotransferase (ALT) elevations which were attributed to external causes rather than to trial interventions.^13,14

NCT05275998

In the first part of this Phase 1b/2a dose-escalation trial, safety data from 30 participants who received single infusions of TMB-365 and TMB-380 (VRC07-523LS) indicated that both bNAbs were safe at all three dose levels studied. No serious or severe side effects were reported. Twenty-three participants reported mild or moderate side effects, and five side effects were considered probably or definitely related to bNAb infusions. Two participants in the mid-dose group had a hypersensitivity reaction (fatigue and chills) to bNAb infusions. Other bNAb-related side effects included coldness in hands and/or feet, fatigue, and sneezing.³²

In the second part of this study, 21 participants received at least one infusion of TMB-365 and TMB-380. Two participants discontinued treatment because of moderately severe drug-related rash. There were no serious or severe side effects, and no acute infusion reactions were reported. (Acute infusion reactions are infusion-related side effects occurring during or shortly after an infusion.) Side effects that were possibly or probably related to bNAb infusions occurred in eight participants and included rash, fatigue, headache, flushing, fever, chills, and aches.¹⁷

ACTG A5357 (NCT03739996)

In this Phase 2 trial, 75 participants initially received oral cabotegravir (CAB) plus two NRTIs (Step 1). Thereafter, 71 participants who tolerated the oral CAB regimen and maintained viral suppression discontinued oral CAB and NRTIs and switched to intramuscular (IM) long acting cabotegravir (CAB LA) plus intravenous (IV) VRC07-523LS for up to 48 weeks (Step 2). During Step 2, one participant discontinued treatment due to a mild infusion reaction that started and resolved on the day of their third VRC07-523LS infusion. Eleven participants had severe side effects that were at least possibly related to CAB LA or VRC07-523LS. Severe side effects that were at least possibly related to VRC07-523LS included chills, feeling unwell, fatigue, generalized aching, narrowing of the blood vessels, low blood pressure, myalgia, and headache. One participant had severe elevated ALT levels, which was possibly related to both CAB LA and VRC07-523LS.^19,33

GS-US-382-5445 (NCT05281510)

In this Phase 2a trial, 20 participants received oral doses of vesatolimod and infusions of the bNAbs VRC07-523LS and CAP256VLS. No treatment-related serious side effects were reported. One participant discontinued vesatolimod because of a side effect. Most of the participants experienced reactions to bNAb infusions, but all of these reactions were mild to moderate in severity and went away within 2 days.²²

Because VRC07-523LS is still being studied, information on possible side effects of the drug is not complete. As testing of VRC07-523LS continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying VRC07-523LS? Where can I get more information about clinical trials studying VRC07-523LS?

Where can I get more information about clinical trials studying VRC07-523LS?

More information about VRC07-523LS-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.

References References

References

1. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Accessed August 5, 2025
2. Treatment Action Group website. Research toward a cure trials. Accessed August 5, 2025
3. Jefferys R. The HIV vaccines and passive immunization pipeline report 2024. Treatment Action Group Pipeline Report 2024. Accessed August 5, 2025
4. National Institute of Allergy and Infectious Diseases (NIAID). A randomized, double blind, controlled, Phase 2 clinical trial to evaluate the safety, tolerability, pharmacokinetics, and neutralization of VRC07-523LS, PGT121.414.LS, and PGDM1400LS broadly neutralizing monoclonal antibodies given intravenously in adult participants without HIV. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 31, 2025. NLM Identifier: NCT06812494. Accessed August 5, 2025
5. HIV Vaccine Trials Network (HVTN). Using antibodies for HIV prevention. Accessed March 25, 2025
6. Snow B. The rise of broadly neutralizing antibodies. AIDS Vaccine Advocacy Coalition (AVAC). Published May 17, 2018. Accessed August 5, 2025
7. National Institute of Allergy and Infectious Diseases (NIAID). Sustained ART-free HIV remission. Accessed August 5, 2025
8. National Institute of Allergy and Infectious Diseases (NIAID). Future directions for HIV treatment research. Accessed August 5, 2025
9. Grobben M, Stuart RA, van Gils MJ. The potential of engineered antibodies for HIV-1 therapy and cure. Curr Opin Virol. 2019;38:70-80. doi:10.1016/j.coviro.2019.07.007. Accessed August 5, 2025
10. International AIDS Vaccine Initiative. A Phase 1/2a open label study of the safety, tolerability, pharmacokinetics and antiviral activity of PGT121, VRC07-523LS and PGDM1400 monoclonal antibodies in HIV-uninfected and HIV-infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 16, 2018. NLM Identifier: NCT03721510. Accessed August 5, 2025
11. Juelg BD, Walker-Sperling VE, Wagh K, et al. Therapeutic efficacy of a triple combination of HIV-1 broadly neutralizing antibodies. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2024; Denver, CO. Accessed August 5, 2025
12. Julg B, Walker-Sperling VEK, Wagh K, et al. Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: a phase 1/2a trial. Nat Med. 2024;30(12):3534-3543. doi:10.1038/s41591-024-03247-5. Accessed August 5, 2025
13. 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 August 5, 2025
14. 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 August 5, 2025
15. Boris Juelg, MD PhD. A safety, immunogenicity and efficacy Phase 1/2a study of a heterologous Ad26.Mos4.HIV, MVA-BN-HIV vaccine regimen plus broadly neutralizing antibodies PGT121, PGDM1400, and VRC07-523LS in HIV-1-infected adults on suppressive ART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 5, 2021. NLM Identifier: NCT04983030. Accessed August 5, 2025
16. TaiMed Biologics Inc. A Phase 1b/2a dose escalation study of the safety, pharmacokinetics, and efficacy of the combination of TMB-365 and TMB-380 in HIV-1 infected individuals suppressed with combination antiretroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 2, 2022. NLM Identifier: NCT05275998. Accessed August 5, 2025
17. Lalezari JP, DeJesus E, Sension MG, et al. A 24-week Phase II maintenance study of TMB-365/TMB-380 Q8W in people with suppressed HIV-1 infection. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 9-12, 2025; San Francisco, CA. Poster 701. Accessed August 5, 2025
18. National Institute of Allergy and Infectious Diseases (NIAID). A study of long-acting cabotegravir plus VRC01LS to maintain viral suppression in adults living with HIV-1. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 9, 2018. NLM Identifier: NCT03739996. Accessed August 5, 2025
19. Taiwo B, Zheng YE, Rodriguez K, et al. Safety and efficacy of VRC07-523LS plus long-acting cabotegravir in the Phase II ACTG A5357 trial. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2024; Denver, CO. Abstract 119. Accessed August 5, 2025
20. Taiwo BO, Zheng Y, Rodriguez K, et al. Phase 2 trial of long-acting cabotegravir and VRC07-523LS for viral suppression in adults with HIV-1: ACTG A5357. Clin Infect Dis. Published online July 15, 2025:ciaf375. doi:10.1093/cid/ciaf375. Accessed August 5, 2025
21. Gilead Sciences. A Phase 2a study to evaluate the safety and tolerability of a regimen of dual anti-HIV envelope antibodies, VRC07-523LS and CAP256V2LS, in a sequential regimen with a TLR7 agonist, vesatolimod, in early antiretroviral-treated HIV-1 clade C-infected women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 7, 2022. NLM Identifier: NCT05281510. Accessed August 5, 2025
22. Dong K, Asari V, Govender V, et al. Evaluation of 2 bNAbs plus vesatolimod in early-treated South African women with HIV-1 during ATI. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 9-12, 2025; San Francisco, CA. Abstract 105. Accessed August 5, 2025
23. National Institute of Allergy and Infectious Diseases (NIAID). A double-blind, randomized, placebo-controlled clinical trial of combination HIV-specific broadly neutralizing monoclonal antibodies combined with ART initiation during acute HIV infection to induce HIV remission. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 30, 2023. NLM Identifier: NCT05719441. Accessed August 5, 2025
24. National Institute of Allergy and Infectious Diseases (NIAID). Phase I/II trial to evaluate the impact of three broadly neutralizing antibodies or analytic treatment interruption on viral reservoir, immune function, and maintenance of HIV suppression in early treated children in Botswana. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 26, 2024. NLM Identifier: NCT06508749. Accessed August 5, 2025
25. University of North Carolina, Chapel Hill. IGHID 11802 - Combination therapy with the novel clearance modality (VRC07-523LS) and the latency reversal agent (vorinostat) to reduce the frequency of latent, resting CD4+ T cell infection (the VOR-07 study). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on: January 10, 2019. NLM Identifier: NCT03803605. Accessed August 5, 2025
26. National Institute of Allergy and Infectious Diseases (NIAID). VRC 607-ACTG A5378: a phase 1, single dose study of the safety and virologic effect of an HIV-1 specific broadly neutralizing human monoclonal antibody, VRC-HIVMAB080-00-AB (VRC01LS) or VRC-HIVMAB075-00-AB (VRC07-523LS), administered intravenously to HIV-infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered July 19, 2016. NLM Identifier: NCT02840474. Accessed August 5, 2025
27. International AIDS Vaccine Initiative. A Phase 1 randomized placebo-controlled clinical trial of the safety, pharmacokinetics and antiviral activity of PGDM1400 and PGT121 and VRC07-523LS monoclonal antibodies in HIV-uninfected and HIV-infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 12, 2017. NLM Identifier: NCT03205917. Accessed August 5, 2025
28. 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 August 5, 2025
29. Henry M. Jackson Foundation for the Advancement of Military Medicine. Approach to control HIV with immune enhancement and vaccination (ACHIEV): safety and efficacy of broadly neutralizing antibodies combined with therapeutic vaccination for the induction of HIV remission. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 31, 2024. NLM Identifier: NCT06484335. Accessed August 5, 2025
30. Centre for the AIDS Programme of Research in South Africa. Phase 1 study to evaluate if broadly neutralizing monoclonal antibodies CAP256V2LS and VRC07-523LS, combined with antiretroviral therapy (ART), will result in sustained virological control following analytical treatment interruption. Pan African Clinical Trials Registry. Trial no.: PACTR202309578224660. Accessed August 5, 2025
31. National Institute of Allergy and Infectious Diseases (NIAID). A Phase I study to evaluate the safety and antiviral activity of two human monoclonal antibodies (VRC07-523LS and PGT121.414.LS) during analytic treatment interruption in participants living with HIV who initiated ART during acute/early HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 25, 2025. NLM Identifier: NCT06987318. Accessed August 5, 2025
32. Lalezari JP, Ramgopal M, Richmond G, et al. A dose escalation study of safety & PK of TMB-365 & TMB-380 in people with suppressed HIV. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2024, 2024; Denver, CO. Poster 640. Accessed August 5, 2025
33. Taiwo B, Zheng YE, Rodriguez K, et al. Safety and efficacy of VRC07-523LS plus long-acting cabotegravir in the Phase II ACTG A5357 trial. Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2024; Denver, CO. Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2024. Accessed August 5, 2025