Observational Study on Anti-Tat Immune Response in HIV-1-infected HAART-treated Adult Subjects (ISS OBS T-002)

• ClinicalTrials.gov Identifier: NCT01024556
• Recruitment Status: Completed
• First Posted: December 2, 2009
• Last Update Posted: March 4, 2016
• Sponsor: Barbara Ensoli, MD
• Information provided by (Responsible Party): Barbara Ensoli, MD, Istituto Superiore di Sanità

Study Description

Brief Summary:

The present study is designed as a prospective observational study directed at evaluating the frequency, magnitude, quality and persistence (primary endpoint) of the anti-Tat immune response in highly active antiretroviral therapy (HAART)-receiving HIV-1 infected individuals, and to prospectively evaluate the immunological, virological and clinical outcome of anti-Tat positive versus anti-Tat negative subjects under successful HAART (secondary endpoint), in order to determine the impact of anti-Tat immunity on HIV disease progression as well as the potential use of anti-Tat immune response assessment for the clinical and therapeutic management of HAART-treated infected patients. This survey provided important information for the design, planning and conduction of future therapeutic vaccine trials based on the HIV-1 Tat protein in HAART-treated patients.

Condition or disease
HIV Infection

Study Design

• Study Type: Observational
• Actual Enrollment: 142 participants
• Time Perspective: Prospective
• Official Title: Observational Study With Additional Diagnostic Procedures on Anti-Tat Immune Response in HIV-1-infected HAART-treated Adult Subjects
• Study Start Date: March 2008
• Actual Study Completion Date: February 2012

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Assessment of anti-Tat antibodies in sera of subjects, and of the proliferative response (CFSE) and the production of γIFN, IL-4 and IL-2 (Elispot) by peripheral blood mononuclear cells (PBMC) in response to Tat.

Secondary Outcome Measures :

1. The decline of CD4+ T cell counts, the increase of HIV plasma viral load or the occurrence of AIDS-defining events were assessed to determine progression to disease.

Biospecimen Retention:   Samples With DNA

whole blood, serum, PBMCs

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Hiv-1-infected haart-treated adult subjects

Criteria

Inclusion Criteria:

• Diagnosis of HIV-1 infection
• To be under successful HAART treatment with plasma viremia <50 copies/ml in the last 6 months prior to initiation of the study, without a history of virologic rebound
• Known CD4+ T cells nadir
• Age ≥ 18 years old
• Signed informed consent

Exclusion Criteria:

• Current therapy with immunomodulators or immunosuppressive drugs, or chemotherapy for neoplastic disorders
• Concomitant treatment for HBV or HCV infection

Contacts and Locations

Locations

Italy

S.M. Goretti Hospital

Latina, Rome, Italy

General Hospital of Bari

Bari, Italy

Spedali Civili di Brescia

Brescia, Italy

General Hospital-University of Ferrara

Ferrara, Italy

A.M. Annunziata Hospital

Florence, Italy

L. Sacco Hospital

Milan, Italy

San Raffaele Hospital

Milan, Italy

General Hospital-University of Modena

Modena, Italy, 41100

San Gallicano Hospital

Rome, Italy

Amedeo di Savoia Hospital

Torino, Italy

Sponsors and Collaborators

Barbara Ensoli, MD

Investigators

• Principal Investigator: Roberto Esposito, MD; Azienda Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy
• Principal Investigator: Giovanni Di Perri, MD; Amedeo di Savoia Hospital, Turin, Italy
• Principal Investigator: Adriano Lazzarin, MD; San Raffaele Hospital - Milan, Italy
• Principal Investigator: Massimo Galli, MD; L. Sacco Hospital- Milan, Italy
• Principal Investigator: Giampiero Carosi, MD; "Spedali Civili" di Brescia , Brescia, Italy
• Principal Investigator: Florio Ghinelli, MD; Azienda Ospedaliero - Universitaria di Ferrara, Ferrara, Italy
• Principal Investigator: Francesco Mazzotta, MD; S. M. Annunziata Hospital, Florence, Italy
• Principal Investigator: Guido Palamara, MD; S. Gallicano Hospital- Rome, Italy
• Principal Investigator: Fabrizio Soscia, MD; S. M. Goretti Hospital- Latina, Italy
• Principal Investigator: Giuseppe Pastore, MD; "Ospedale Policlinico Consorziale"-Bari, Italy

More Information

Additional Information:

Related Info 

Publications of Results:

Ensoli B, Bellino S, Tripiciano A, Longo O, Francavilla V, Marcotullio S, Cafaro A, Picconi O, Paniccia G, Scoglio A, Arancio A, Ariola C, Ruiz Alvarez MJ, Campagna M, Scaramuzzi D, Iori C, Esposito R, Mussini C, Ghinelli F, Sighinolfi L, Palamara G, Latini A, Angarano G, Ladisa N, Soscia F, Mercurio VS, Lazzarin A, Tambussi G, Visintini R, Mazzotta F, Di Pietro M, Galli M, Rusconi S, Carosi G, Torti C, Di Perri G, Bonora S, Ensoli F, Garaci E. Therapeutic immunization with HIV-1 Tat reduces immune activation and loss of regulatory T-cells and improves immune function in subjects on HAART. PLoS One. 2010 Nov 11;5(11):e13540. doi: 10.1371/journal.pone.0013540.

Other Publications:

André P, Groettrup M, Klenerman P, de Giuli R, Booth BL Jr, Cerundolo V, Bonneville M, Jotereau F, Zinkernagel RM, Lotteau V. An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13120-4.

Arya SK, Guo C, Josephs SF, Wong-Staal F. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science. 1985 Jul 5;229(4708):69-73.

Ensoli B, Barillari G, Salahuddin SZ, Gallo RC, Wong-Staal F. Tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients. Nature. 1990 May 3;345(6270):84-6.

Ensoli B, Buonaguro L, Barillari G, Fiorelli V, Gendelman R, Morgan RA, Wingfield P, Gallo RC. Release, uptake, and effects of extracellular human immunodeficiency virus type 1 Tat protein on cell growth and viral transactivation. J Virol. 1993 Jan;67(1):277-87.

Ensoli B, Fiorelli V, Ensoli F, Cafaro A, Titti F, Buttò S, Monini P, Magnani M, Caputo A, Garaci E. Candidate HIV-1 Tat vaccine development: from basic science to clinical trials. AIDS. 2006 Nov 28;20(18):2245-61. Review.

Monini P, Cafaro A, Srivastava IK, Moretti S, Sharma VA, Andreini C, Chiozzini C, Ferrantelli F, Cossut MR, Tripiciano A, Nappi F, Longo O, Bellino S, Picconi O, Fanales-Belasio E, Borsetti A, Toschi E, Schiavoni I, Bacigalupo I, Kan E, Sernicola L, Maggiorella MT, Montin K, Porcu M, Leone P, Leone P, Collacchi B, Palladino C, Ridolfi B, Falchi M, Macchia I, Ulmer JB, Buttò S, Sgadari C, Magnani M, Federico MP, Titti F, Banci L, Dallocchio F, Rappuoli R, Ensoli F, Barnett SW, Garaci E, Ensoli B. HIV-1 tat promotes integrin-mediated HIV transmission to dendritic cells by binding Env spikes and competes neutralization by anti-HIV antibodies. PLoS One. 2012;7(11):e48781. doi: 10.1371/journal.pone.0048781. Epub 2012 Nov 13.

Bellino S, Tripiciano A, Picconi O, Francavilla V, Longo O, Sgadari C, Paniccia G, Arancio A, Angarano G, Ladisa N, Lazzarin A, Tambussi G, Nozza S, Torti C, Focà E, Palamara G, Latini A, Sighinolfi L, Mazzotta F, Di Pietro M, Di Perri G, Bonora S, Mercurio VS, Mussini C, Gori A, Galli M, Monini P, Cafaro A, Ensoli F, Ensoli B. The presence of anti-Tat antibodies in HIV-infected individuals is associated with containment of CD4+ T-cell decay and viral load, and with delay of disease progression: results of a 3-year cohort study. Retrovirology. 2014 Jun 24;11:49. doi: 10.1186/1742-4690-11-49.

Ensoli B, Cafaro A, Monini P, Marcotullio S, Ensoli F. Challenges in HIV Vaccine Research for Treatment and Prevention. Front Immunol. 2014 Sep 8;5:417. doi: 10.3389/fimmu.2014.00417. eCollection 2014. Review.

Ensoli F, Cafaro A, Casabianca A, Tripiciano A, Bellino S, Longo O, Francavilla V, Picconi O, Sgadari C, Moretti S, Cossut MR, Arancio A, Orlandi C, Sernicola L, Maggiorella MT, Paniccia G, Mussini C, Lazzarin A, Sighinolfi L, Palamara G, Gori A, Angarano G, Di Pietro M, Galli M, Mercurio VS, Castelli F, Di Perri G, Monini P, Magnani M, Garaci E, Ensoli B. HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: results of a randomized phase II exploratory clinical trial. Retrovirology. 2015 Apr 29;12:33. doi: 10.1186/s12977-015-0151-y.

Cafaro A, Tripiciano A, Sgadari C, Bellino S, Picconi O, Longo O, Francavilla V, Buttò S, Titti F, Monini P, Ensoli F, Ensoli B. Development of a novel AIDS vaccine: the HIV-1 transactivator of transcription protein vaccine. Expert Opin Biol Ther. 2015;15 Suppl 1:S13-29. doi: 10.1517/14712598.2015.1021328. Epub 2015 Jun 22. Review.

• Responsible Party: Barbara Ensoli, MD, PHD, Istituto Superiore di Sanità
• ClinicalTrials.gov Identifier: NCT01024556
• Other Study ID Numbers: ISS OBS T-002
• First Posted: December 2, 2009
• Last Update Posted: March 4, 2016
• Last Verified: March 2016

Keywords provided by Barbara Ensoli, MD, Istituto Superiore di Sanità:

HIV, HAART

Additional relevant MeSH terms:

HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases