Observational Study on Anti-Tat Immune Response in HIV-1-infected HAART-treated Adult Subjects

NCT01024556 | Completed

• 1 other identifier: ISS OBS T-002
• Study Type: observational
• Target: 142
• Locations: 1 country
• Sites: 10

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.

Conditions

HIV Infection

Keywords

HIV, HAART

Outcome Measures

Primary Outcomes (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 Outcomes (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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Hiv-1-infected haart-treated adult subjects

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Barbara Ensoli, MD: lead

Study Sites (10)

S.M. Goretti Hospital

Latina, Rome, Italy

Location

General Hospital of Bari

Bari, Italy

Location

Spedali Civili di Brescia

Brescia, Italy

Location

General Hospital-University of Ferrara

Ferrara, Italy

Location

A.M. Annunziata Hospital

Florence, Italy

Location

L. Sacco Hospital

Milan, Italy

Location

San Raffaele Hospital

Milan, Italy

Location

General Hospital-University of Modena

Modena, 41100, Italy

Location

San Gallicano Hospital

Rome, Italy

Location

Amedeo di Savoia Hospital

Torino, Italy

Location

Related Publications (12)

• Andre 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. doi: 10.1073/pnas.95.22.13120.

  PMID: 9789051 BACKGROUND

• 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. doi: 10.1126/science.2990040.

  PMID: 2990040 BACKGROUND

• 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. doi: 10.1038/345084a0.

  PMID: 2184372 BACKGROUND

• 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. doi: 10.1128/JVI.67.1.277-287.1993.

  PMID: 8416373 BACKGROUND

• Ensoli B, Fiorelli V, Ensoli F, Cafaro A, Titti F, Butto 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. doi: 10.1097/QAD.0b013e3280112cd1. No abstract available.

  PMID: 17117011 BACKGROUND

• 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, Butto 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.

  PMID: 23152803 BACKGROUND

• 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, Foca 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.

  PMID: 24961156 BACKGROUND

• 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.

  PMID: 25250026 BACKGROUND

• 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.

  PMID: 25924841 BACKGROUND

• Cafaro A, Tripiciano A, Sgadari C, Bellino S, Picconi O, Longo O, Francavilla V, Butto 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.

  PMID: 26096836 BACKGROUND

• 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.

  PMID: 21085635 RESULT

• Tripiciano A, Picconi O, Moretti S, Sgadari C, Cafaro A, Francavilla V, Arancio A, Paniccia G, Campagna M, Pavone-Cossut MR, Sighinolfi L, Latini A, Mercurio VS, Pietro MD, Castelli F, Saracino A, Mussini C, Perri GD, Galli M, Nozza S, Ensoli F, Monini P, Ensoli B. Anti-Tat immunity defines CD4+ T-cell dynamics in people living with HIV on long-term cART. EBioMedicine. 2021 Apr;66:103306. doi: 10.1016/j.ebiom.2021.103306. Epub 2021 Apr 7.

  PMID: 33839064 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, serum, PBMCs

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PHD

Study Record Dates

• First Submitted: December 1, 2009
• First Posted: December 2, 2009
• Study Start: March 1, 2008
• Study Completion: February 1, 2012
• Last Updated: March 4, 2016

Record last verified: 2016-03

Locations

IT (10)