Drug Database: Vesatolimod

What is vesatolimod? What is vesatolimod?

What is vesatolimod?

Vesatolimod is an investigational drug that is being studied to treat HIV. Vesatolimod belongs to a group of HIV drugs called immune modulators.^3,6 Immune modulators (also called immunomodulators) are substances that help to activate, boost, or restore normal immune function.

Vesatolimod’s potential role as a latency-reversing agent has also been evaluated in preclinical and clinical trials; however, results thus far have been mixed.^3,7–10

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.

Select clinical trials of vesatolimod Select clinical trials of vesatolimod

Select clinical trials of vesatolimod

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 to evaluate the safety and efficacy of a combination regimen in adults who initiated suppressive antiretroviral therapy (ART) during acute HIV. The combination regimen includes therapeutic HIV vaccines, vesatolimod, and the broadly neutralizing antibodies (bNAbs) 3BNC117-LS (also known as teropavimab or GS-5423) and 10-1074-LS (also known as zinlirvimab or GS-2872).¹¹

Study Names: AEILIX-003; NCT05364035

Phase: 2a
Status: This study has been completed
Location: Spain
Purpose: The purpose of this study was to evaluate the safety, immunogenicity, and efficacy of therapeutic HIV vaccines and vesatolimod in adults who had received early ART treatment.⁴
Selected Study Results: Results presented at CROI 2023 and IAS 2023 and published in Nature Communications (2025) showed that the combination of therapeutic HIV vaccines with 10 doses of vesatolimod was safe with only one serious side effect reported, which was unrelated to the study drugs. Therapeutic HIV vaccines given with vesatolimod stimulated strong immune responses. Vaccine-specific T-cell responses contributed to improved viral control after participants underwent an analytical treatment interruption of ART.^12-14
Additional Published Material:

• Commun Med (Lond) article, 2025: Predictors of virological outcomes after analytical interruption of antiretroviral therapy and HTI vaccination in early treated people with HIV-1

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 given in combination with vesatolimod in women with clade C HIV who had received early ART treatment.⁵
Selected Study Results: Results presented at CROI 2025 and EACS 2025 showed that vesatolimod and the bNAbs VRC07-523LS and CAP256V2LS were safe, with no treatment-related serious side effects reported. Eighteen participants (90%) experienced infusion-related reactions, most of which were mild in severity and went away within 2 days. One participant had a side effect resulting in discontinuation of vesatolimod. During an analytical treatment interruption of ART, varying patterns of viral control were seen among the 20 participants.^15,16
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

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

Other studies looking at vesatolimod have been completed. These include the following Phase 1 trials.

• GS-US-382-1450 (NCT02858401): A Phase 1b dose-escalation study that evaluated vesatolimod's safety and effect on viral load in adults with HIV who had viral suppression on ART. This study has been completed, and results are published in Clin Infect Dis (2021).¹⁷
• GS-US-382-3961 (NCT03060447): A Phase 1b study that evaluated the safety and efficacy of vesatolimod in adults with HIV who had undetectable or low viral load levels before initiating ART and viral suppression on ART. This study has been completed, and results are available from Sci Transl Med (2021) and CROI 2023.¹⁸
  

What side effects might vesatolimod cause? What side effects might vesatolimod cause?

What side effects might vesatolimod cause?

One goal of HIV research is to identify safe new drugs that have fewer side effects. The following side effects were observed in some of the studies of vesatolimod listed above.

AELIX-003 (NCT04364035)

In this Phase 2a trial, 33 participants received therapeutic HIV vaccines plus vesatolimod and 17 participants received placebo. Most of the participants receiving therapeutic HIV vaccines plus vesatolimod experienced a drug-related side effect, all of which were mild or moderate in severity. Among the participants receiving therapeutic HIV vaccines plus vesatolimod, the most common side effects related to the study drugs were injection-site pain, influenza-like illness, headache, and fatigue. None of the drug-related side effects led to treatment discontinuation. No serious side effects related to the study drugs occurred.^4,12,14

GS-US-382-5445 (NCT05281510)

In this Phase 2a trial, 20 participants received up to 10 oral doses of vesatolimod and infusions of the bNAbs VRC07-523LS and CAP256VLS. Treatment-related side effects, most of which were mild, occurred in 18 participants. Two participants had severe treatment-related side effects (fever and chills). The most common treatment-related side effects were infusion-related reactions, headache, increased heart rate, fever, and chest discomfort. No serious side effects related to the study treatments were reported. One participant developed a mild side effect, called cytokine release syndrome, that led to discontinuation of vesatolimod. (Cytokine release syndrome is caused by immune cells rapidly releasing a large amount of cytokines in the body. This condition can occur after treatment with certain immune therapies).^15,16

GS-US-382-1450 (NCT02858401)

In this Phase 1b dose-escalation trial, 48 participants received multiple doses of either vesatolimod or placebo. Side effects related to vesatolimod included fatigue, headache, myalgia, and fever. Drug-related side effects occurred more frequently in each of the two highest vesatolimod dose groups compared to the placebo group. Study drug-related side effects were mild, temporary, and did not occur with each dose. There were no drug-related serious side effects or discontinuations due to a side effect.³

GS-US-382-3961 (NCT03060447)

In this Phase 1b trial, 25 participants received 10 doses of vesatolimod or placebo. Most of the side effects that occurred during the study were mild to moderate in severity. Drug-related side effects occurred in 53% of participants in the vesatolimod group and 13% of participants in the placebo group. The majority of side effects related to vesatolimod were mild, temporary, flu-like symptoms — chills, headache, swollen lymph nodes, fatigue, and fever. One participant receiving vesatolimod had chronic inflammation of the stomach lining, which was considered a serious side effect. Another participant receiving vesatolimod had severe drug-related cases of gout; joint pain; and sciatica (a nerve problem affecting the legs). However, these drug-related side effects went away in the participant without the need for treatment. None of the participants discontinued treatment because of drug-related side effects.⁸

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

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

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

More information about vesatolimod-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 Center for Biotechnology Information. PubChem compound summary for CID 46241268, vesatolimod. Accessed February 10, 2026
2. Gilead Sciences website. Pipeline. Accessed February 10, 2026
3. Riddler SA, Para M, Benson CA, et al. Vesatolimod, a toll-like receptor 7 agonist, induces immune activation in virally suppressed adults living with human immunodeficiency virus–1. Clin Infect Dis. 2021;72(11):e815-e824. doi:10.1093/cid/ciaa1534. Accessed February 10, 2026
4. Aelix Therapeutics. A Phase IIa randomised, double-blind, placebo-controlled study of HIV-1 vaccines MVA.HTI and ChAdOx1.HTI with TLR7 agonist vesatolimod (GS-9620) in early treated HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 5, 2020. NLM Identifier: NCT04364035. Accessed February 10, 2026
5. 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 February 10, 2026
6. Treatment Action Group website. Research toward a cure trials. Accessed February 10, 2026
7. Tsai A, Irrinki A, Kaur J, et al. Toll-like receptor 7 agonist GS-9620 induces HIV expression and HIV-specific immunity in cells from HIV-infected individuals on suppressive antiretroviral therapy. J Virol. 2017;91(8):e02166-16. doi:10.1128/JVI.02166-16. Accessed February 10, 2026
8. SenGupta D, Brinson C, DeJesus E, et al. The TLR7 agonist vesatolimod induced a modest delay in viral rebound in HIV controllers after cessation of antiretroviral therapy. Sci Transl Med. 2021;13(599):eabg3071. doi:10.1126/scitranslmed.abg3071. Accessed February 10, 2026
9. Lim SY, Osuna CE, Hraber PT, et al. TLR7 agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral therapy. Sci Transl Med. 2018;10(439):eaao4521. doi:10.1126/scitranslmed.aao4521. Accessed February 10, 2026
10. Del Prete GQ, Alvord WG, Li Y, et al. TLR7 agonist administration to SIV-infected macaques receiving early initiated cART does not induce plasma viremia. JCI Insight. 4(11):e127717. doi:10.1172/jci.insight.127717. Accessed February 10, 2026
11. 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 February 10, 2026
12. Mothe B, Curran A, de Quirós JCLB, et al. A placebo-controlled randomized trial of the HTI immunogen vaccine and vesatolimod. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 19-22, 2023; Seattle, WA. Poster 433. Accessed February 10, 2026
13. Mothe B, Bailon L, Curran A, et al. T-cell responses induced by HTI vaccines and vesatolimod correlate with improved control of HIV rebound. Abstract presented at: International AIDS Society (IAS) Conference on HIV Science; July 23-26, 2023; Brisbane, Australia. Abstract LBEPB20. Accessed February 10, 2026
14. Bailón L, Moltó J, Curran A, et al. Safety, immunogenicity and effect on viral rebound of HTI vaccines combined with a TLR7 agonist in early-treated HIV-1 infection: a randomized, placebo-controlled phase 2a trial. Nat Commun. 2025;16:2146. doi:10.1038/s41467-025-57284-w. Accessed February 10, 2026
15. 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 February 10, 2026
16. Lim D, Fu Olivia, Liu Xiaopeng, et al. Safety and analytical treatment interruption outcomes in a clinical trial of 2 broadly neutralizing antibodies plus vesatolimod in early-treated South African women with clade C HIV-1. European AIDS Conference; October 15-18, 2025; Paris, France. Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2025. Accessed February 10, 2026
17. Gilead Sciences. A Phase 1b, randomized, blinded, placebo-controlled dose-escalation study of the safety and biological activity of GS-9620 in HIV-1 infected, virologically suppressed adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 26, 2016. NLM Identifier: NCT02858401. Accessed February 10, 2026
18. Gilead Sciences. A Phase 1b, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of GS-9620 in antiretroviral treated HIV-1 infected controllers. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 17, 2017. NLM Identifier: NCT03060447. Accessed February 10, 2026