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

HIV Infection Clinical Trial

— ISS OBS T-002  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01024556
• Other study ID #: ISS OBS T-002
• Status: Completed
• Phase: N/A
• First received: December 1, 2009
• Last updated: March 3, 2016
• Start date: March 2008
• Est. completion date: February 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• HIV Infection

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	Amedeo di Savoia Hospital	Torino

Sponsors (1)

Lead Sponsor	Collaborator
Barbara Ensoli, MD

Country where clinical trial is conducted

Italy, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. — 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, 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. — 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, Lati — View Citation

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. — 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

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of anti-Tat antibodies in sera of subjects, and of the proliferative response (CFSE) and the production of ?IFN, IL-4 and IL-2 (Elispot) by peripheral blood mononuclear cells (PBMC) in response to Tat.			No
Secondary	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.			No

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