Drug Database: PGT121

What is PGT121? What is PGT121?

What is PGT121?

PDT121 is an investigational drug that is being studied as a possible strategy to treat people with HIV. PGT121 belongs to a group of drugs called broadly neutralizing antibodies (bNAbs).¹

A long-acting form of PGT121, called PGT121.414.LS, is also under study for HIV treatment and/or prevention.^1,4,5

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.^6,7

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.^6,8,9

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.^8,10

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 This record focuses on the study of PGT121 as a treatment for HIV.

Select clinical trials of PGT121 Select clinical trials of PGT121

Select clinical trials of PGT121

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.¹¹
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 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.^12,13

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 bNAbs (PGT121, PGDM1400, and 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.¹⁴

Study Names: A5388; NCT05719441

Phase: 2
Status: See the ClinicalTrials.gov record for this study’s status.
Location: 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.¹⁵

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 the maintenance of HIV suppression in children in Botswana who had started ART early in life.¹⁶

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

Additional studies evaluating PGT121 or PGT121.414.LS for HIV treatment have been completed or are planned, including the following Phase 1 trials:

• IAVI T001 (NCT02960581): A study that evaluated the safety, tolerability, pharmacokinetics, and antiviral activity of PGT121 in adults with and without HIV. This study has been completed, and results are available from CROI 2019 and Nature Medicine (2021).¹⁷
• 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).¹⁸
• 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.¹⁹

What side effects might PGT121 cause? What side effects might PGT121 cause?

What side effects might PGT121 cause?

One goal of HIV research is to identify new drugs that have fewer side effects. In the IAVI T003 study (NCT03721510) discussed under the previous section, PGT121, VRC07-523LS, and PGDM1400 infusions were reported to be generally safe and well tolerated. Four serious and/or severe side effects occurred during the study but all were considered unrelated to the study bNAbs.^11,12

Because PGT121 is still being studied, information on possible side effects of the drug is not complete. As testing of PGT121 continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying PGT121? Where can I get more information about clinical trials studying PGT121?

Where can I get more information about clinical trials studying PGT121?

More information about PGT121-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. Treatment Action Group website. Research toward a cure trials. Accessed June 4, 2025
2. Mahomed S, Garrett N, Capparelli E, et al. Assessing the safety and pharmacokinetics of the monoclonal antibodies, VRC07-523LS and PGT121 in HIV negative women in South Africa: study protocol for the CAPRISA 012A randomised controlled phase I trial. BMJ Open. 2019;9(7):e030283. doi:10.1136/bmjopen-2019-030283. Accessed June 4, 2025
3. National Institute of Allergy and Infectious Diseases (NIAID) news release, dated August 6, 2024. Broadly neutralizing antibodies evaluated in many HIV cure strategies. Accessed June 4, 2025
4. Jefferys R. The HIV vaccines and passive immunization pipeline report 2024. Treatment Action Group Pipeline Report 2024. Accessed June 4, 2025
5. 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 June 4, 2025
6. HIV Vaccine Trials Network (HVTN). Using antibodies for HIV prevention. Accessed June 4, 2025
7. Snow B. The rise of broadly neutralizing antibodies. AIDS Vaccine Advocacy Coalition (AVAC). Published May 17, 2018. Accessed June 4, 2025
8. National Institute of Allergy and Infectious Diseases (NIAID). Sustained ART-free HIV remission. Accessed June 4, 2025
9. National Institute of Allergy and Infectious Diseases (NIAID). Future directions for HIV treatment research. Accessed June 4, 2025
10. 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 June 4, 2025
11. 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 June 4, 2025
12. 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 June 4, 2025
13. 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 June 4, 2025
14. 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 June 4, 2025
15. 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 June 4, 2025
16. 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 June 4, 2025
17. International AIDS Vaccine Initiative. A Phase 1 randomized placebo-controlled clinical trial of the safety, pharmacokinetics and antiviral activity of PGT121 monoclonal antibody (mAb) in HIV-uninfected and HIV-infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 18, 2016. NLM Identifier: NCT02960581. Accessed June 4, 2025
18. 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 June 4, 2025
19. 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 June 4, 2025

Last Reviewed: June 4, 2025