Clinical trial NCT01029548: Observational Study on Anti-Tat Immune Response in HIV-1-infected Asymptomatic Adult Subjects
Official title: Observational Study With Additional Diagnostic Procedures on Anti-Tat Immune Response in HIV-1-infected Asymptomatic Adult Subjects
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: HIV
Therapeutic Vaccine
Lead sponsor: Istituto Superiore di Sanità
Sponsor class: OTHER
First posted: 2009-12-10
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Asymptomatic HIV infected individuals

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 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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 γIFN, IL-4 and IL-2 (Elispot) by peripheral blood mononuclear cells.
Secondary outcomes:
measure: 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
Other outcomes:
Locations:
city: Latina
country: Italy
facility: S.M. Goretti Hospital
state: Rome
city: Bari
country: Italy
facility: General Hospital of Bari
city: Brescia
country: Italy
facility: Spedali Civili di Brescia
city: Ferrara
country: Italy
facility: General Hospital-University of Ferrara
city: Florence
country: Italy
facility: A.M. Annunziata Hospital
city: Milan
country: Italy
facility: L. Sacco Hospital
city: Milan
country: Italy
facility: San Raffaele Hospital
city: Modena
country: Italy
facility: General Hospital-University of Modena
city: Rome
country: Italy
facility: San Gallicano Hospital
city: Turin
country: Italy
facility: Giovanni Di Perri
Study officials:
affiliation: A.M. Annunziata Hospital Florence, Italy
name: Francesco Mazzotta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: General Hospital of Bari
name: Giuseppe Pastore, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: General Hospital-University of Ferrara
name: Florio Ghinelli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: General Hospital-University of Modena
name: Roberto Esposito, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: L.Sacco Hospital - MI
name: Massimo Galli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: S.M. Goretti Hospital Latina
name: Fabrizio Soscia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: San Gallicano Hospital - Rome
name: Guido Palamara, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: San Raffaele Hospital - Milan
name: Adriano Lazzarin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Spedali Civili - Brescia
name: Giampiero Carosi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Amedeo di Savoia Hospital - Turin
name: Giovanni Di Perri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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, Butto 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. doi: 10.1086/428909. Epub 2005 Mar 14.
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. doi: 10.1073/pnas.90.16.7719.
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.
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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, 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.
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, 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.