Mechanism of Action: HIV-1 CCR5 antagonist. Monomeric DAPTA (mDAPTA) is a reformulated monomeric form of peptide T ([D-Ala1] Peptide T Amide; DAPTA), a synthetic octapeptide compound derived from the gp120 V-2 region of HIV. Peptide T is a selective CCR5 co-receptor antagonist that prevents viral entry by directly binding to the CCR5 co-receptor and subsequently inhibiting the interaction between HIV-1 gp120 and CCR5.4-7In vitro, mDAPTA has been shown to inhibit the release of CXCR4- and CCR5-tropic HIV from CD8-depleted PBMCs isolated from HIV-uninfected patients and HIV-infected patients with viral load less than 50 copies/mL.8
mDAPTA has also been studied for its antiviral effect on the JC virus in individuals with progressive multifocal leukoencephalopathy (PML).9
Half-life (T½): In a Phase I study involving participants with AIDS or AIDS-related complex (ARC), peptide T demonstrated biphasic plasma kinetics following intravenous (IV) or intranasal (IN) administration, with a first compartment half-life of 30 to 60 minutes and a second compartment plasma clearance time of 4 to 6 hours.10
Metabolism/Elimination: In a Phase I study, participants with AIDS or ARC received peptide T via IV or IN administration. After administration, the drug could not be detected in urine.10
Resistance: In a small study of 11 HIV-infected participants receiving peptide T either alone or in combination with their current ART for up to 32 weeks, no obvious CCR5 to CXCR4 co-receptor shift occurred, and treatment-resistant viruses did not emerge.11
Select Clinical Trials
: Not available
: Not available
: Not available
: The purpose of this study was to evaluate the antiviral and immunological benefits of peptide T.
: Participants were long-term HIV-infected participants with stable viral loads. Participants were either treatment-naive or treatment-experienced.
: Participants received peptide T 2 mg administered intranasally 3 times a day for up to 32 weeks, given either alone or in combination with current ART.11
Selected Study Results
- Peptides article, 2003: Antiviral and immunological benefits in HIV patients receiving intranasal peptide T (DAPTA).
: National Institute of Mental Health (NIMH)
: The purpose of this study was to determine the ability of peptide T to treat HIV-associated cognitive impairment.
: Participants were HIV-infected adults with cognitive impairment. Participants had not received ART within 4 weeks of study entry or had been receiving stable ART for at least 12 weeks prior to entry.
: Participants received peptide T 2 mg administered intranasally 3 times a day for 6 months versus similarly administered placebo.12,13
: During this study, participant cerebrospinal fluid (CSF) and peripheral blood samples were frozen and stored. At a later time, the stored CSF and blood samples were used to conduct a retrospective analysis on the ability of peptide T to reduce viral load in a subgroup of participants from the original trial sample.6,7
Selected Study Results
Monomeric DAPTA – reformulation of peptide T
Study Identifier: NCT00951743
Sponsor: Rapid Laboratories Inc.
Study Purpose: The purpose of this study is to evaluate the safety and toxicity of mDAPTA and the ability of mDAPTA to eliminate treatment-resistant HIV in PBMCs.
Study Population: Participants are HIV-infected, treatment-experienced adults who have received continuous ART for at least 6 months and who have HIV RNA <200 copies/mL for at least 3 months prior to study entry.
Dosing: Participants will receive mDAPTA 0.01 mg administered intranasally twice daily for 24 weeks versus similarly administered placebo, each in combination with ART.14
* The recruitment status of this study is unknown.
In a small study investigating the antiviral and immune benefits of peptide T in 11 HIV-infected participants, peptide T was considered safe, with no drug-associated toxicities reported. No nasal pathologies were detected.11
In the Phase II study (NCT00000392
) of peptide T in patients with HIV-associated cognitive impairment, researchers indicated no clinically significant toxic effects associated with peptide T use. However, mood disturbance severity was significantly greater in the peptide T group versus the placebo group, with 7 Grade 3 events occurring in the peptide T group versus 1 in the placebo group. Investigators indicated that this difference could be attributed to more severe mood disturbances at study entry in the peptide T arm participants than in the placebo arm participants. In addition, rash was significantly more severe in the peptide T group than in the placebo group. Participants receiving peptide T had a higher prevalence (borderline significant) of nasal congestion, proteinuria, and eosinophilia than participants receiving placebo.12,13
Drug interactions related to monomeric DAPTA use are currently unknown.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: https://chem.sis.nlm.nih.gov/chemidplus/rn/106362-34-9. Last accessed on June 26, 2017.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on June 26, 2017.
- RAPID Pharmaceuticals: Press Release, dated March 4, 2014. RAPID Acquires All Peptide T Clinical Data. Available at: http://www.rapidpharma.com/rapid-acquires-all-peptide-t-clinical-data/. Last accessed on June 17, 2015.
- Polianova MT, Ruscetti FW, Pert CB, Ruff MR. Chemokine receptor-5 (CCR5) is a receptor for the HIV entry inhibitor peptide T (DAPTA). Antiviral Res. 2005 Aug;67(2):83-92. Available at: http://www.researchgate.net/profile/Maria_Polianova/publication/8658079_Update_on_D-ala-peptide_T-amide_%28DAPTA%29_a_viral_entry_inhibitor_that_blocks_CCR5_chemokine_receptors/links/5436af3e0cf2643ab9881308.pdf. Last accessed on June 26, 2017.
- RAPID Pharmaceuticals website. Monomeric DAPTA – the long path to discovery. Available at: http://www.rapidpharma.com/en/research-developement/technology-platform/path-to-discovery.html. Last accessed on March 31, 2014.
- Pollicita M, Ruff MR, Pert CB, et al. Profound anti-HIV-1 activity of DAPTA in monocytes/macrophages and inhibition of CCR5-mediated apoptosis in neuronal cells. Antivir Chem Chemother. 2007;18(5):285-95. Available at: http://journals.sagepub.com/doi/pdf/10.1177/095632020701800504. Last accessed on June 26, 2017.
- Goodkin K, Vitiello B, Lyman WD, et al. Cerebrospinal and peripheral human immunodeficiency virus type 1 load in a multisite, randomized, double-blind, placebo-controlled trial of D-Ala1-peptide T-amide for HIV-1-associated cognitive-motor impairment. J Neurovirol. 2006 Jun;12(3):178-89. Available at: http://www.researchgate.net/profile/Benedetto_Vitiello/publication/6909865_Cerebrospinal_and_peripheral_human_immunodeficiency_virus_type_1_load_in_a_multisite_randomized_double-blind_placebo-controlled_trial_of_D-Ala1-peptide_T-amide_for_HIV-1-associated_cognitive-motor_impairment/links/09e4150805c0ab6304000000.pdf. Last accessed on June 26, 2017.
- Agrawal L, Ducoudret O, Baichoo N, Laznicka M, Ruff M, Pert C. mDAPTA, a potent CCR5 receptor blocker, prevents viral recovery from CD8-depleted patient PBMCs with VL< 50 background. Abstract presented at: International AIDS Conference; July 18-23, 2010; Vienna, Austria. Abstract TUPE0017. Available at: http://www.abstract-archive.org/. Last accessed on June 26, 2017.
- Rapid Pharmaceuticals. PML. Available at: http://www.rapidpharma.com/pml-rap-101/. Last accessed on June 2, 2016.
- Ruff MR, Smith C, Kingan T, et al. Pharmacokinetics of peptide T in patients with acquired immunodeficiency syndrome (AIDS). Prog Neuropsychopharmacol Biol Psychiatry. 1991;15(6):791-801. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1763193. Last accessed on June 26, 2017.
- Polianova MT, Ruscetti FW, Pert CB, et al. Antiviral and immunological benefits in HIV patients receiving intranasal peptide T (DAPTA). Peptides. 2003 Jul;24(7):1093-8. Available at: http://www.rapidpharma.com/uploads/media/2003-02_Publication.pdf. Last accessed on March 31, 2014.
- Heseltine PN, Goodkin K, Atkinson JH, et al. Randomized Double-blind Placebo-Controlled Trial of Peptide T for HIV-Associated Cognitive Impairment. Arch Neurol. 1998 Jan;55(1):41-51. Available at: http://jamanetwork.com/journals/jamaneurology/fullarticle/773550. Last accessed on June 26, 2017.
- National Institute of Mental Health (NIMH). Phase II Study of the Efficacy of Peptide T in HIV-Positive Individuals With Cognitive Impairment. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 17, 2000. NLM Identifier: NCT00000392. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00000392. Last accessed on June 26, 2017.
- Rapid Laboratories Inc. Safety and Efficacy of ADAPTAVIR's Ability to Eliminate Treatment-Resistant Infectious Virus in the Blood Cellular Reservoir (PBMCs) of HIV Patients With Suppressed Plasma Viral Load. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 31, 2009. NLM Identifier: NCT00951743. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00951743. Last accessed on June 26, 2017.
Last Reviewed: June 26, 2017