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 donors without HIV and from donors with HIV with viral load levels of less than 50 copies/mL.8
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.9
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.9
Resistance: In a small study of 11 participants with HIV 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.10
Select Clinical Trials
Study Identifier: Not available
Sponsor: Not available
Phase: Not available
Status: This study has been completed.
Study Purpose: The purpose of this study was to evaluate the antiviral and immunological benefits of peptide T.
Study Population: Participants had HIV for a mean of 17 years and had stable viral load levels between 500 and 25,000 copies/ml. Some participants were treatment-naive; others were treatment-experienced.
Dosing: 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.10
Selected Study Results:
: National Institute of Mental Health (NIMH)
: This study has been completed.
: The purpose of this study was to determine the ability of peptide T to treat HIV-associated cognitive impairment.
: Participants were adults with HIV with cognitive impairment. Participants either had not used ART within 4 weeks of study entry or had been on 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.11,12
: 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.
Status: The recruitment status of this study is unknown.
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 treatment-experienced adults with HIV 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.13
In a small study investigating the antiviral and immune benefits of peptide T in 11 participants with HIV, peptide T was considered safe, with no drug-associated toxicities reported. No nasal pathologies were detected.10
In the Phase II study (NCT00000392
) of peptide T in participants with HIV-associated cognitive impairment, researchers indicated no clinically significant toxic effects associated with peptide T use. However, the severity of mood disturbances was significantly greater in the peptide T group than in the placebo group, with 7 Grade 3 events occurring in the peptide T group and 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 group than in the placebo group. 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.11,12
Drug interactions related to monomeric DAPTA use are currently unknown.
- United States National Library of Medicine. ChemIDplus Advanced: Adaptavir. https://chem.nlm.nih.gov/chemidplus/rn/106362-34-9. Accessed: August 7, 2018.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed: August 7, 2018.
- RAPID Pharmaceuticals. Press Release, dated March 4, 2014. RAPID acquires all peptide T clinical data. https://web.archive.org/web/20150513080447/http://www.rapidpharma.com/rapid-acquires-all-peptide-t-clinical-data/. Accessed: August 7, 2018.
- Polianova MT, Ruscetti FW, Pert CB, Ruff MR. Chemokine receptor-5 (CCR5) is a receptor for the HIV entry inhibitor peptide T (DAPTA). Antivir Res. 2005;67(2):83-92.
- RAPID Pharmaceuticals website. Monomeric DAPTA – the long path to discovery. http://www.rapidpharma.com/en/research-developement/technology-platform/path-to-discovery.html. Accessed: August 7, 2018.
- 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.
- 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;12(3):178-89.
- 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. http://www.abstract-archive.org/Abstract/Share/4495. Accessed: August 7, 2018.
- 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.
- 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;55(1):41-51.
- 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. https://clinicaltrials.gov/ct2/show/NCT00000392. Accessed: August 7, 2018.
- 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. https://clinicaltrials.gov/ct2/show/NCT00951743. Accessed: August 7, 2018.
Last Reviewed: August 7, 2018