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 living 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.^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 (ART). 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 VRC07-523LS can prevent HIV infection in people who do not have the virus.³ 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.⁹
Selected Study Results: Results 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, 36% of the participants who completed follow-up had viral suppression through the end of the study (Week 44).¹⁰

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.^11,12
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.¹²

Study Name: NCT04983030

Phase: 1/2a
Status: This study is currently 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.¹³

Study Name: NCT05275998

Phase: 1b/2a
Status: This study is ongoing, but not recruiting participants.
Locations: United States
Purpose: The purpose of this dose-escalation trial is to evaluate the safety, pharmacokinetics, and antiviral activity of the antibodies TMB-365 and TMB-380 (VRC07-523LS) in individuals with viral suppression on ART.¹⁴
Selected Study Results: Available safety and pharmacokinetic results presented at CROI 2024 showed that a single intravenous (IV) infusion of TMB-365 and TMB-380, administered at three different dose levels, was generally safe with no serious or severe side effects reported. Pharmacokinetic data demonstrated the feasibility of an every 8-week dosing schedule, which investigators will evaluate in the Phase 2a portion of the trial.¹⁵

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.¹⁶
Selected Study Results: Results presented at CROI 2024 demonstrated that CAB LA plus VRC07-523LS was safe and capable of maintaining viral suppression in most participants. Eleven (15%) participants had a severe side effect that was 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.¹⁷ 

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

Phase: 2a
Status: This study is ongoing, but not recruiting participants.
Location: South Africa
Purpose: The purpose of this trial is to evaluate the safety and tolerability of the bNAbs VRC07-523LS and CAP256V2LS with the immune modulator vesatolimod in early ART-treated women with clade C HIV.¹⁸

Study Names: A5388; NCT05719441

Phase: 2
Status: This study is currently recruiting participants.
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.¹⁹

Study Names: IMPAACT 2042; Tatelo Plus Study; NCT06508749

Phase: 1/2 
Status: See the ClinicalTrials.gov record for this study’s status.
Location: Botswana  
Purpose: The purpose of this open-label study is to evaluate the impact of three bNAbs (PGDM1400LS, VRC07-523LS, and PGT121.414.LS) or analytical treatment interruption on viral reservoir, immune function, and maintenance of HIV suppression in early ART-treated children in Botswana.²⁰

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 early-phase trials:

• VOR-07 study (NCT03803605): A Phase 1 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 (2022).²¹
• VRC 607/ACTG A5378 (NCT02840474): A Phase 1 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 2019.²²
• IAVI T002 (NCT03205917): A Phase 1 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).²³
• ACTG A5386 (NCT04340596): A Phase 1 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 currently recruiting participants.²⁴
• RV 630/DELIVER-01 (NCT06484335): A Phase 1 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 ART during acute HIV infection. See the ClinicalTrials.gov record for this study’s status.²⁵
• PACTR202309578224660: A Phase 1 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.²⁶ 

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 considered unrelated to the study bNAbs.^9,10

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.^11,12

NCT05275998

In this Phase 1b/2a dose-escalation trial, early 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.¹⁵

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 (15%) participants had severe side effects that were considered 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.^17,27

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 VRC01-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 September 10, 2024
2. Treatment Action Group website. Research toward a cure trials. Accessed September 10, 2024
3. Jefferys R. The HIV vaccines and passive immunization pipeline report 2024. Treatment Action Group Pipeline Report 2024. Accessed September 10, 2024
4. HIV Vaccine Trials Network (HVTN). Using antibodies for HIV prevention. Accessed September 10, 2024
5. Snow B. The rise of broadly neutralizing antibodies. AIDS Vaccine Advocacy Coalition (AVAC). Published May 17, 2018. Accessed September 10, 2024
6. National Institute of Allergy and Infectious Diseases (NIAID). Sustained ART-free HIV remission. Accessed September 10, 2024
7. National Institute of Allergy and Infectious Diseases (NIAID). Future directions for HIV treatment research. Accessed September 10, 2024
8. 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 September 10, 2024
9. 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 September 10, 2024
10. 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 September 10, 2024
11. 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 September 10, 2024
12. 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 September 10, 2024
13. 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 September 10, 2024
14. 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 September 10, 2024
15. 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 September 10, 2024
16. 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 September 10, 2024
17. 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 September 10, 2024
18. 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 September 10, 2024
19. 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 September 10, 2024
20. 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 September 10, 2024
21. 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 September 10, 2024
22. 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 September 10, 2024
23. 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 September 10, 2024
24. 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 September 10, 2024
25. 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 September 10, 2024
26. 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 September 10, 2024
27. 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 September 10, 2024