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

HIV Infections Clinical Trial

— ISS OBS T-003  

Official title:

Observational Study With Additional Diagnostic Procedures on Anti-Tat Immune Response in HIV-1-infected Asymptomatic Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01029548
• Other study ID #: ISS OBS T-003
• Status: Completed
• Phase: N/A
• First received: December 9, 2009
• Last updated: March 3, 2016
• Start date: April 2008
• Est. completion date: May 2012

Study information

• Verified date: March 2016
• Source: Istituto Superiore di Sanità
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Observational

Clinical Trial 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 HIV-1 infected asymptomatic individuals, and to prospectively evaluate the immunological, virological and clinical outcome of anti-Tat positive versus anti-Tat negative drug naїve subjects (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 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 asymptomatic subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• To be clinically asymptomatic HIV-1 infected individuals with CD4+ T cell counts =400/µL

• To be naïve for antiretroviral therapy

• Levels of plasma viremia =100,000 copies/ml at baseline

• Age = 18 years

• Signed informed consent

Exclusion Criteria:

• Current therapy with immunomodulators or immunosuppressive drugs or chemotherapy for neoplastic disorders

• Concomitant treatment for HBV or HCV infection

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• HIV Infections

Locations

Country	Name	City	State
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	S.M. Goretti Hospital	Latina	Rome
Italy	L. Sacco Hospital	Milan
Italy	San Raffaele Hospital	Milan
Italy	General Hospital-University of Modena	Modena
Italy	San Gallicano Hospital	Rome
Italy	Giovanni Di Perri	Turin

Sponsors (1)

Lead Sponsor	Collaborator
Barbara Ensoli, MD

Country where clinical trial is conducted

Italy, 

References & Publications (9)

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, Mercur — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Rezza G, Fiorelli V, Dorrucci M, Ciccozzi M, Tripiciano A, Scoglio A, Collacchi B, Ruiz-Alvarez M, Giannetto C, Caputo A, Tomasoni L, Castelli F, Sciandra M, Sinicco A, Ensoli F, Buttò S, Ensoli B. The presence of anti-Tat antibodies is predictive of long-term nonprogression to AIDS or severe immunodeficiency: findings in a cohort of HIV-1 seroconverters. J Infect Dis. 2005 Apr 15;191(8):1321-4. Epub 2005 Mar 14. — View Citation

Rodman TC, To SE, Hashish H, Manchester K. Epitopes for natural antibodies of human immunodeficiency virus (HIV)-negative (normal) and HIV-positive sera are coincident with two key functional sequences of HIV Tat protein. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7719-23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Specific humoral and cellular immune responses to Tat will be monitored by assessing anti-Tat specific antibodies in sera, proliferative response (CFSE) and production of ?IFN, IL-4 and IL-2 (Elispot) by peripheral blood mononuclear cells.
Secondary	The decline of CD4+ T cells count, the increase of the HIV plasma viral load or the occurrence of AIDS-defining events will be assessed to determine the progression to disease

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