Drug Database: Vesatolimod

What is vesatolimod? What is vesatolimod?

What is vesatolimod?

Vesatolimod is an investigational drugthat is being studied to treat HIV infection. 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: See the ClinicalTrial.gov record for this study’s status. 
Locations: United States and Brazil
Purpose: The purpose of this study is the evaluate the safety and efficacy of a combination regimen in adults who initiated suppressive antiretroviral therapy (ART) during acute HIV infection. The combination regimen includes therapeutic HIV vaccines, vesatolimod, and two broadly neutralizing antibodies (bNAbs) (GS-5423 [also known as 3BNC117-LS] and GS-2872 [also known as 10-1074-LS]).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 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 outcomes after participants underwent an analytical treatment interruption of ART.^12,13

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

Phase: 2a
Status: This study is currently 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 given in combination with vesatolimod in women with clade C HIV who had received early ART treatment.⁵

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 or are ongoing. These include the following Phase 1 trials.

• GS-US-382-1450 (NCT02858401): A Phase 1b dose-escalation study that evaluated the safety and virologic effect of vesatolimod in adults with HIV who had viral suppression on ART. This study has been completed, and results are published in Clin Infect Dis (2021).¹⁴
• 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 2023.¹⁵
• GS-US-382-1587 (NCT05458102): A Phase 1 drug-drug interaction study of vesatolimod in adults with HIV who have viral suppression on ART. This study is ongoing, but not recruiting participants.¹⁶
   

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 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, the combination of therapeutic HIV vaccines and vesatolimod was safe. One participant had a serious side effect, which was deemed unrelated to the study drugs.^4,12

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. No participants discontinued the study because of 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 November 1, 2023
2. Gilead Sciences website. Pipeline. Accessed November 1, 2023
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 November 1, 2023
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 November 1, 2023
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 November 1, 2023
6. Treatment Action Group website. Research toward a cure trials. Accessed November 1, 2023
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 November 1, 2023
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 November 1, 2023
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 November 1, 2023
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 November 1, 2023
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 November 1, 2023
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 November 1, 2023
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 November 1, 2023
14. 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 November 1, 2023
15. 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 November 1, 2023
16. Gilead Sciences. A Phase 1, open-label, multicohort study to evaluate the impact of inhibitors and inducers of cytochrome P450 enzyme (CYP)3A and/or P-glycoprotein (P-gp) on the pharmacokinetics (PK) of vesatolimod (VES) in virologically suppressed adults with HIV-1 on antiretroviral therapy (ART). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 11, 2022. NLM Identifier: NCT05458102. Accessed November 1, 2023