Clinical Study of TUTI-16 in Asymptomatic HIV-1 Infected Subjects (THYMON-08001)

This protocol represents the first in human study of TUTI-16, and is being conducted to establish the safety and human immunogenicity (anti-HIV-1 Tat titers) of subcutaneously administered TUTI-16. Activity of TUTI-16 will also be determined in minimizing HIV-1 viral loads and sustaining CD4+ T-cell levels.

HIV-1 Tat protein, a virally encoded toxin, is secreted by HIV-1 infected cells and acts on uninfected cells, rendering them permissive for HIV-1 replication. HIV-1 Tat enhances chronic viral replication and induces immune suppression. Antibodies to Tat inhibit this Tat-mediated transcellular activation in vitro and minimize chronic plasma viremia. HIV-1 Tat activities can be blocked in vitro and in vivo by anti-Tat antibodies. The Thymon Universal Tat Immunogen (TUTI-16) is a fully synthetic, self-adjuvanting lipopeptide vaccine that is water soluble and administered by subcutaneous injection. In preclinical studies, a priming dose and a three week boost in rats induced a high titer antibody response to the eight known distinct epitope variants of HIV-1 Tat protein. These antibodies block the function of the HIV-1 Tat protein (toxin), which is essential to the maintenance of chronic HIV-1 viremia. Therefore, TUTI-16 has potential as a therapeutic vaccine for HIV-1 in humans.

Inclusion Criteria: Males and Females Age ≥18 and ≤50 years at Screening HIV-1 seropositive asymptomatic and in generally good health no prior anti-retroviral therapy within 6 months of screening viral load ≥ 3,000 ≤ 100,000 HIV-1 RNA copies/mL CD4+ T-cell count ≥ 400/mm3. Exclusion Criteria: Pregnant/nursing females positive for HBV or HCV acute Herpetic event any clinically significant out-of range laboratory value subject is unable or unwilling to discontinue during the study participation in another investigational drug/vaccine study within 30 days preceding the first injection of investigational agent in this study.

Goldstein G, Chicca JJ. Exploratory clinical studies of a synthetic HIV-1 Tat epitope vaccine in asymptomatic treatment-naive and antiretroviral-controlled HIV-1 infected subjects plus healthy uninfected subjects. Hum Vaccin Immunother. 2012 Apr;8(4):479-85. doi: 10.4161/hv.19184. Epub 2012 Feb 16.