THV01Other Names: THV01-1, THV01-2 Drug Class: Therapeutic Vaccines Organization: Theravectys Phase of Development: I/IIa
(Compound details obtained from Treatment Action Group website,1 Theravectys website,2 and IAS Towards an HIV Cure Symposium 2015 Poster PE62 LB3)
Mechanism of Action: Therapeutic vaccine. THV01 is a therapeutic HIV vaccine regimen based on lentiviral vectors.3 Therapeutic vaccines are being investigated as an immunotherapeutic approach to correcting HIV-associated immune dysfunction, such as impaired dendritic cell (DC) responses to HIV and suboptimal adaptive immune responses (including HIV-specific T cell responses).4-7 A therapeutic vaccine may potentially increase the effectiveness of ART, simplify ART regimens, or allow for periodic structured treatment interruptions. A successful therapeutic vaccine would either completely eradicate the virus or improve an individual’s immune response sufficiently to suppress viral replication without ART. In either case, a therapeutic vaccine would help to circumvent a lifetime of ART.8
THV01 consists of two vaccines, THV01-1 and THV01-2, which are intended to be administered in succession as a prime-boost regimen. Both THV01-1 and THV02-2 are live lentiviral vector vaccines that are produced by recombinant technology and are derived from the NL4-3 strain of HIV-1. The vectors are modified to ensure that they are nonvirulent, virtually replication incompetent, and self-inactivating. Each vaccine vector carries a transgene encoding for the same HIV-1 clade B Gag, Pol, and Nef protein fragments. The THV01 regimen functions by targeting DCs, whereby 1) the transgene is integrated into the host cell genome and subsequently transcribed and processed into epitopes on the DC surface; 2) host cellular immune responses — specifically, cytotoxic T lymphocytes (CTLs) — are induced; and 3) the transduced DCs and HIV-infected cells are eliminated by the host. THV01 is being studied as a potential strategy to functionally cure HIV and has demonstrated the ability to induce vaccine-specific CD4 and CD8 cell responses in a Phase I/II clinical trial.3,9
Select Clinical Trials
Study Identifier: THV01-11-01; NCT02054286
Sponsor: Theravectys S.A.
Status: This study is ongoing, but not recruiting participants.
Study Purpose: The purpose of this study is to evaluate the safety and immunogenicity of the THV01 prime/boost vaccine regimen administered at three different dose levels.
- Participants are adults with clade B HIV and have been receiving a triple-ARV regimen (two NRTIs + one boosted PI or two NRTIs + one NNRTI) for more than a year prior to baseline. For more than 60 days prior to baseline, participants must have been receiving two NRTIs + a ritonavir-boosted PI (darunavir + ritonavir or lopinavir + ritonavir).
- Participants have never had HIV RNA >150,000 copies/mL (except for measurements during primary infection) and have had HIV RNA ≤50 copies/mL for the 12 months prior to screening.
- Participants have had CD4 counts ≥300 cells/mm3 since the time of diagnosis. From the time of diagnosis to initiation of ART, participants have had at least one CD4 count <500 cells/mm3. At baseline, participants have CD4 counts ≥600 cells/mm3.3,10
Selected Study Results:
- IAS Towards an HIV Cure Symposium, 2015: A first-in-human Phase I/II trial demonstrates the safety & the immunogenicity of a lentiviral-based therapeutic HIV vaccine eliciting potent polyfunctional multispecific CD8 & CD4 T-cell responses in HIV-infected individuals
In the Phase I/IIa trial (NCT02054286) assessing three escalating doses of THV01 in 38 total participants, analysis through Week 36 found no notable safety issues associated with the vaccine regimen and no occurrences of serious adverse events (SAEs). The incidence of treatment-emergent adverse events (AEs) was similar across each of the three THV01 groups and the placebo group. The only reported difference was with injection site pain, which was more common in the highest THV01 dosing group.3
Drug-drug interactions associated with THV01 are currently unknown.
- Treatment Action Group website. Research toward a cure trials. http://www.treatmentactiongroup.org/cure/trials. Accessed March 27, 2019.
- Theravectys website. Clinical trials. http://www.theravectys.com/clinical-trials/. Accessed March 27, 2019.
- Toussaint H, Sarry E, Bejanariu A, et al. A first-in-human Phase I/II trial demonstrates the safety and the immunogenicity of a lentiviral-based therapeutic HIV vaccine eliciting potent polyfunctional multispecific CD8 and CD4 T-cell responses in HIV-infected individuals. Poster presented at: International AIDS Society (IAS) Towards an HIV Cure Symposium; July 18-19, 2015; Vancouver, Canada. Poster PE62 LB. https://www.iasociety.org/Web/WebContent/File/HIV_Cure_Symposium_2015/Posters2/PE62_Toussaint.pdf. Accessed March 27, 2019.
- Lederman M, Rodriguez B, Sieg S. Immunopathogenesis of HIV Infection. In: Coffey S, Volberding P, eds. HIV InSite Knowledge Base. University of California San Francisco; 2004. http://hivinsite.ucsf.edu/InSite?page=kb-00&doc=kb-02-01-04. Accessed March 27, 2019.
- Miller E, Bhardwaj N. Advances in dendritic cell immunotherapies for HIV-1 infection. Expert Opin Biol Ther. 2014;14(11):1545-1549.
- Smith PL, Tanner H, Dalgleish A. Developments in HIV-1 immunotherapy and therapeutic vaccination. F1000Prime Rep. 2014;6(43). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047951/. Accessed March 27, 2019.
- Routy J-P, Boulassel M-R, Yassine-Diab B, et al. Immunologic activity and safety of autologous HIV RNA–electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy. Clin Immunol. 2010;134(2):140-147.
- Graziani GM, Angel JB. Evaluating the efficacy of therapeutic HIV vaccines through analytical treatment interruptions. J Int AIDS Soc. 2015;18(1):20497.
- The Joint Research Centre of the European Commission. GMO Register: Notification Number B/BE/12/BVW1. THV01-1; THV01-2 – Summary notification information format for the release of genetically modified organisms other than higher plants in accordance with article 11 of directive 2011/18/EC; Version 2.0; 04/27/2012. http://gmoinfo.jrc.ec.europa.eu/bsnifs-gmo/B-BE-12-BVW1.pdf. Accessed March 27, 2019.
- Theravectys S.A. A multi-center, randomized, double-blind, placebo-controlled Phase I/II trial to compare the safety, tolerability and immunogenicity of the therapeutic THV01 vaccination at 5.10E+6 TU (transducing unit) , 5.10E+7 TU (transducing unit) or 5.10E+8 TU (transducing unit) doses to placebo in HIV-1 clade B infected patients under highly active antiretroviral therapy (HAART). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 1, 2014. NLM Identifier: NCT02054286. https://clinicaltrials.gov/ct2/show/NCT02054286. Accessed March 27, 2019.
Last Reviewed: March 27, 2019