Drug Database: VRC01

What is VRC01?What is VRC01?

What is VRC01?

VRC01 is an investigational drug that is currently being studied as a possible strategy to treat people with HIV. It has also been studied for HIV prevention. VRC01 belongs to a group of HIV drugs called broadly neutralizing antibodies (bNAbs).^3-5

A long-acting form of VRC01, called VRC01LS, has also been studied for HIV treatment and has been studied for HIV treatment and prevention.^3,6 

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.^7,8

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.^7,9,10

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.^9,11

Researchers are also trying to find out if giving bNAbs to people who do not have HIV can help protect them from getting the virus.^4,5 This record discusses the study of VRC01 for both HIV treatment and prevention.

Select clinical trials of VRC01Select clinical trials of VRC01

Select clinical trials of VRC01

VRC01 for HIV treatment

Study Names: IMPAACT 2008; NCT03208231

Phase: 1/2
Status: This study has been completed.
Location: Botswana, Brazil, Malawi, and Zimbabwe
Purpose: The purpose of this study was to evaluate the safety and efficacy of VRC01 plus antiretroviral therapy (ART) in clearing the latent HIV reservoir in infants who were initiating ART.¹³
Selected Study Results: Results presented at AIDS 2022 showed that there were no safety concerns with VRC01 administered subcutaneously in infants. The addition of VRC01 to ART was no more effective than ART alone in reducing viral reservoir size. Researchers noted that baseline resistance to ART and VRC01, as well as low VRC01 trough concentrations in some infants, may have contributed to the diminished efficacy of VRC01.¹³

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 safety and efficacy of VRC01LS and the investigational bNAb 10-1074 in maintaining viral suppression in children who had received early ART treatment.¹⁵
Selected Study Results: Results published in Sci Transl Med (2023) and presented at CROI 2022 showed that dual bNAb treatment with VRC01LS and 10-1074 was safe and effective. Among study participants who underwent an analytical treatment interruption of ART, 44% of the participants 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.^15,16 

Study Names: RV 397; NCT02664415

Phase: 2
Status: This study has been completed.
Location: Thailand
Purpose: The purpose of this study was to evaluate the safety of VRC01 and efficacy of VRC01 in preventing viral rebound in participants undergoing an analytical treatment interruption of ART.¹⁷
Selected Study Results: Results published in Lancet HIV (2019) showed that infusions of VRC01 given to individuals who had started ART during acute HIV infection were safe, with no serious side effects reported during the study. However, VRC01 did not have a significant impact on the number of participants maintaining viral suppression at 24 weeks after ART interruption.¹⁸

Study Names: (1) HVTN 804/HPTN 095; NCT04801758 and (2) HVTN 805/HPTN 093; NCT04860323

Phase: Not available
Status: HVTN 804/HPTN 095 has been completed. HVTN 805/HPTN 093 is ongoing, but not recruiting participants.
Location: (1) HVTN 804/HPTN 095 – United States, Brazil, and Peru (2) HVTN 805/HPTN 093 – Sub-Saharan Africa
Purpose: The purpose of these studies is to evaluate the ability of the immune system to control viral load levels during an analytical treatment interruption of ART in participants who received VRC01 or placebo and acquired HIV while enrolled in the antibody-mediated prevention (AMP) studies, HVTN 704/HPTN 085 or HVTN 703/HPTN 081.^19,20
Selected Study Results: 

HVTN 804/HPTN 095: Early results from the HVTN 804/HPTN 095 trial were presented at HIVR4P 2024. Among 17 participants who had acquired HIV during the HVTN 704/HPTN 085 AMP study, there was no evidence of viral control during analytical treatment interruption of ART. The time from when participants started ART treatment interruption to when they had viral rebound greater than 200 copies/mL and met the criteria for ART re-initiation was no different for participants who had received VRC01 and participants who had received placebo. One participant had a moderately severe side effect related to ART interruption and experienced symptoms of acute retroviral syndrome or acute HIV.^21,22

HVTN 805/HPTN 093: Early observations from the HVTN 805/HPTN 093 trial were presented at AIDS 2022. Thus far, 11 African women who had acquired HIV during the HVTN 703/HPTN 081 AMP study enrolled to undergo analytical treatment interruption of ART. Eight of the 11 women met ART re-initiation criteria and resuppressed after restarting ART. The median time from when participants started ART treatment interruption to when they met criteria for ART re-initiation was 17.1 weeks. Four participants had at least one significant viral load decline while off ART, indicating possible temporary immunologic viral control. There were no serious side effects or side effects (of moderate severity or higher) related to interrupting ART.²³ 

Additional early-phase studies investigating HIV treatment with VRC01 or VRC01LS have been or are being conducted. Some of these studies include:

• RV 398 (NCT02591420): A Phase 1 study that evaluated the safety and antiviral effects of a single infusion of VRC01 in adults with acute HIV infection who received ART simultaneously or one week later. This study has been completed, and results are available from CROI 2023.²⁴
• VRC 607/ACTG A5378 (NCT02840474): A Phase 1 trial that evaluated the safety and antiviral effects of the long-acting bNAbs VRC01LS and VRC07-523LS in treatment-naive adults with HIV. This study has been completed and results are available from IAS 2019.²⁵
• IMPAACT P1115 (NCT02140255): A Phase 1/2 trial evaluating the use of early intensive ART regimens to achieve HIV remission in infants. One of the regimens studied will include the use of VRC01 added to ART. This study is currently recruiting participants. Results thus far are available from CROI 2024 and The Lancet HIV (2024).²⁶ 

VRC01 for HIV prevention

Study Names: (1) HVTN 704/HPTN 085 AMP Study; NCT02716675 and (2) HVTN 703/HPTN 081 AMP Study; NCT02568215

Phase: 2b
Status: These studies have been completed.
Location: (1) HVTN 704/HPTN 085 – United States, Brazil, Peru, and Switzerland (2) HVTN 703/HPTN 081 – Sub-Saharan Africa 
Purpose: The purpose of these studies was to evaluate the safety and efficacy of VRC01 administered every 8 weeks in preventing HIV-1 infection among adults who were at risk of acquiring HIV.^4,5,27
Selected Study Results: Results published in the New England Journal of Medicine (2021) showed that overall, VRC01 did not significantly protect participants from acquiring HIV in either trial. The overall lack of efficacy was due to a low percentage of VRC01-sensitive virus circulating in the regions where the trials were conducted. When looking at the effectiveness of VRC01 infusions in preventing the acquisition of VRC01-sensitive HIV strains in participants from both trials, VRC01 was 75% effective. The number and severity of side effects were similar across treatment groups.²⁷
Additional Published Material: 

• J Acquir Immune Defic Syndr, 2022: Infusion reactions after receiving the broadly neutralizing antibody VRC01 or placebo to reduce HIV-1 acquisition: results from the Phase 2b antibody-mediated prevention randomized trials

Additional studies evaluating VRC01 or VRC01LS for HIV prevention have been completed, including the Phase 1 IMPAACT P1112 trial (NCT02256631) that looked at the safety and pharmacokinetics of three bNAbs (VRC01, VRC01LS, and VRC07-523LS) in HIV-exposed infants who were at increased risk of mother-to-child HIV transmission.⁶ Results to this trial are available from J Infect Dis (2020) and J Infect Dis (2021).

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

What side effects might VRC01 cause?What side effects might VRC01 cause?

What side effects might VRC01 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 VRC01 listed above.

IMPAACT 2008 (NCT03208231)

In the Phase 1/2 IMPAACT 2008 trial, 61 infants initiating ART enrolled to receive either four subcutaneous doses of VRC01 plus ART or ART only. Ninety percent of infants had local injection-site reactions, all of which were of moderate intensity or lower.^12,13

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.^14,16

RV 397 (NCT02664415)

In this Phase 2 study, 14 participants received VRC01 monotherapy and five participants received placebo. Infusion-related side effects occurred with 30.3% of VRC01 infusions and with 37.5% of placebo infusions. Most infusion-related side effects were mild, except for one case of moderate infusion-site bruising and one case of severe hives, both of which occurred in a participant receiving VRC01. The case of hives occurred during the participant’s first dose of VRC01 and led to study withdrawal.^17,18

HVTN 704/HPTN 085 (NCT02716675) and HVTN 703/HPTN 081 (NCT02568215)

In these two Phase 2b prevention studies, the number and severity of side effects that occurred during the trials was similar across VRC01 and placebo treatment groups. Also, the percentage of participants experiencing reactogenic side effects to VRC01 infusions was similar across groups.²⁷ (Reactogenic side effects are short-term side effects that occur during or shortly after receiving a vaccine. Examples of reactogenic side effects include injection-site pain or tenderness and fever.)

Because VRC01 is still being studied, information on possible side effects of the drug is not complete. As testing of VRC01 continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying VRC01?Where can I get more information about clinical trials studying VRC01?

Where can I get more information about clinical trials studying VRC01?

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.

ReferencesReferences

References

1. National Center for Biotechnology Information. PubChem Substance Record for SID 472419986, VRC-01, Source: FDA Global Substance Registration System (GSRS). Accessed November 4, 2024
2. Lynch RM, Boritz E, Coates EE, et al. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Sci Trans Med. 2015;7(319):319ra206. doi:10.1126/scitranslmed.aad5752. Accessed November 4, 2024
3. Treatment Action Group website. Research toward a cure trials. Accessed November 4, 2024
4. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 2b study to evaluate the safety and efficacy of VRC01 broadly neutralizing monoclonal antibody in reducing acquisition of HIV-1 infection among men and transgender persons who have sex with men. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 17, 2016. NLM Identifier: NCT02716675. Accessed November 4, 2024
5. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 2b study to evaluate the safety and efficacy of VRC01 broadly neutralizing monoclonal antibody in reducing acquisition of HIV-1 infection in women in Sub-Saharan Africa. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 1, 2015. NLM Identifier: NCT02568215. Accessed November 4, 2024
6. National Institute of Allergy and Infectious Diseases (NIAID). Open-label, dose-escalating, Phase I study to determine safety and pharmacokinetic parameters of subcutaneous (SC) VRC01, VRC01LS, and VRC07-523LS, potent anti-HIV neutralizing monoclonal antibodies, in HIV-1-exposed infants. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 1, 2014. NLM Identifier: NCT02256631. Accessed November 4, 2024
7. HIV Vaccine Trials Network (HVTN). Using antibodies for HIV prevention. Accessed November 4, 2024
8. Snow B. The rise of broadly neutralizing antibodies.  AIDS Vaccine Advocacy Coalition (AVAC). Published May 17, 2018. Accessed November 4, 2024
9. National Institute of Allergy and Infectious Diseases (NIAID). Sustained ART-free HIV remission. Accessed November 4, 2024
10. National Institute of Allergy and Infectious Diseases (NIAID). Future directions for HIV treatment research. Accessed November 4, 2024
11. 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 November 4, 2024
12. National Institute of Allergy and Infectious Diseases (NIAID). Phase I/II multisite, randomized, controlled study of monoclonal antibody VRC01 with combination antiretroviral therapy to promote clearance of HIV-1-infected cells in infants. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered June 30, 2017. NLM Identifier: NCT03208231. Accessed November 4, 2024
13. Khaitan A, Lindsey J, Capparelli E, et al. Phase I/II study of monoclonal antibody VRC01 with early antiretroviral therapy to promote clearance of HIV-1 infected cells in infants (IMPAACT 2008). Abstract presented at: International AIDS Conference; Montreal, Canada and Virtual; July 29–August 2, 2022. Abstract OALBB0102. Accessed November 4, 2024
14. 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). October 12, 2018. NLM Identifier: NCT03707977. Accessed November 4, 2024
15. 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 November 4, 2024
16. Shapiro RL, Ajibola G, Maswabi K, et al. Broadly neutralizing antibody treatment maintained HIV suppression in children with favorable reservoir characteristics in Botswana. Sci Transl Med. 2023;15(703):eadh0004. doi:10.1126/scitranslmed.adh0004. Accessed November 4, 2024
17. National Institute of Allergy and Infectious Diseases (NIAID). Safety and therapeutic efficacy of the broadly neutralizing HIV-1 specific monoclonal antibody VRC01 during analytic treatment interruption in patients who initiated antiretroviral therapy during early acute HIV infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 20, 2016. NLM Identifier: NCT02664415. Accessed November 4, 2024
18. Crowell TA, Colby DJ, Pinyakorn S, et al. VRC01 in acutely treated HIV-infected adults: a randomised, double-blind, placebo-controlled trial. Lancet HIV. 2019;6(5):e297-e306. doi:10.1016/S2352-3018(19)30053-0. Accessed November 4, 2024
19. HIV Vaccine Trials Network. Antiretroviral analytical treatment interruption (ATI) to assess immunologic and virologic responses in participants who received VRC01 or placebo and became HIV-infected during HVTN 704/HPTN 085. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 1, 2021. NLM Identifier: NCT04801758. Accessed November 4, 2024
20. HIV Vaccine Trials Network. Antiretroviral analytical treatment interruption (ATI) to assess immunologic and virologic responses in participants who initiated ART in early HIV infection after having received VRC01 or placebo in HVTN 703/HPTN 081. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 14, 2021. NLM Identifier: NCT04860323. Accessed November 4, 2024
21. Karuna S, Gallardo-Cartagena J, De La Grecca R, et al. Analytical treatment interruption (ATI) in Peru among MSM, trans & gender non-conforming (GNC) individuals with early ART initiation +/- VRC01 proximate to HIV acquisition: stakeholder engagement & early clinical data. Abstract presented at: HIV Research for Prevention (HIVR4P); October 6-10, 2024; Lima, Peru. Abstract OA0605. Accessed November 4, 2024
22. Gallardo-Cartagena J. Analytical treatment interruption (ATI) in Peru: stakeholder engagement & early clinical data. Slides presented at: HIV Research for Prevention (HIVR4P); October 6-10, 2024; Lima, Peru. Accessed November 4, 2024
23. Karuna S, Bar K, DeCamp A, et al. Analytical treatment interruption (ATI) among African women with early ART initiation with or without VRC01 circulating at HIV acquisition: study design and early observations of viral rebound and control. Poster presented at: International AIDS Conference; July 29-August 2, 2022; Montreal, Canada and Virtual. Poster EPLBB08. Accessed November 4, 2024
24. National Institute of Allergy and Infectious Diseases (NIAID). Safety and virologic effect of a human monoclonal antibody (VRC01) administered intravenously to adults during early acute HIV infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 28, 2015. NLM Identifier: NCT02591420. Accessed November 4, 2024
25. 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 November 4, 2024
26. National Institute of Allergy and Infectious Diseases (NIAID). Very early intensive treatment of HIV-infected infants to achieve hiv remission: a Phase I/II proof of concept study. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 13, 2014. NLM Identifier: NCT02140255. Accessed November 4, 2024
27. Corey L, Gilbert PB, Juraska M, et al. Two randomized trials of neutralizing antibodies to prevent HIV-1 acquisition. N Engl J Med. 2021;384(11):1003-1014. doi:10.1056/NEJMoa2031738. Accessed November 4, 2024