Background: The phase II multicenter, randomized, open label, therapeutic trial (ISS T-002, Clinicaltrials.gov NCT00751595) was aimed at evaluating the immunogenicity and the safety of the biologically active HIV-1 Tat protein administered at 7.5 or 30 μg, given 3 or 5 times monthly, and at exploring immunological and virological disease biomarkers. The study duration was 48 weeks, however, vaccinees were followed until the last enrolled subject reached the 48 weeks. Results: The vaccine was safe and well tolerated and induced anti-Tat Abs in most patients (79%), with the highest frequency and durability in the Tat 30 μg groups (89%) particularly when given 3 times (92%). Vaccination promoted a durable and significant restoration of T, B, natural killer (NK) cells, and CD4<sup>+</sup> and CD8<sup>+</sup> central memory subsets. Moreover, a significant reduction of blood proviral DNA was seen after week 72, particularly under PI-based regimens and with Tat 30 μg given 3 times (30 μg, 3x), reaching a predicted 70% decay after 3 years from vaccination with a half-life of 88 weeks. This decay was significantly associated with anti-Tat IgM and IgG Abs and neutralization of Tat-mediated entry of oligomeric Env in dendritic cells, which predicted HIV-1 DNA decay. Finally, the 30 μg, 3x group was the only one showing significant increases of NK cells and CD38<sup>+</sup>HLA-DR<sup>+</sup>/CD8<sup>+</sup> T cells, a phenotype associated with increased killing activity in elite controllers. Conclusions: Anti-Tat immune responses are needed to restore immune homeostasis and effective anti-viral responses capable of attacking the virus reservoir. Thus, Tat immunization represents a promising pathogenesis-driven intervention to intensify HAART efficacy.
HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA : Results of a randomized phase II exploratory clinical trial / F. Ensoli, A. Cafaro, A. Casabianca, A. Tripiciano, S. Bellino, O. Longo, V. Francavilla, O. Picconi, C. Sgadari, S. Moretti, M.P.R. Cossut, A. Arancio, C. Orlandi, L. Sernicola, M.T. Maggiorella, G. Paniccia, C. Mussini, A. Lazzarin, L. Sighinolfi, G. Palamara, A. Gori, G. Angarano, M. Di Pietro, M. Galli, V.S. Mercurio, F. Castelli, G. Di Perri, P. Monini, M. Magnani, E. Garaci, B. Ensoli. - In: RETROVIROLOGY. - ISSN 1742-4690. - 12:1(2015 Apr 29).
|Titolo:||HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA : Results of a randomized phase II exploratory clinical trial|
|Parole Chiave:||Antibodies; CD38<sup>+</sup>HLA-DR<sup>+</sup>/CD8<sup>+</sup> T cells; HAART; HIV-1; Neutralization; Proviral DNA; Tat protein; Vaccine; AIDS Vaccines; Acquired Immunodeficiency Syndrome; Adult; Antibodies, Neutralizing; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; Follow-Up Studies; HIV Antibodies; Humans; Immunoglobulin G; Immunoglobulin M; Italy; Leukocytes; Male; Middle Aged; Treatment Outcome; Young Adult; tat Gene Products, Human Immunodeficiency Virus; Viral Load; Virology; Infectious Diseases|
|Settore Scientifico Disciplinare:||Settore MED/17 - Malattie Infettive|
|Data di pubblicazione:||29-apr-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1186/s12977-015-0151-y|
|Appare nelle tipologie:||01 - Articolo su periodico|