• It will be measured by the induction, magnitude and persistence of the humoral and cellular immune responses to Tat and by comparing the immunogenicity of a 3/5 immunizations of the different vaccine doses, 7.5 microg and 30 microg at week 24 and 48
  

• The Secondary Endpoint will be focused on adverse events, including any significant change in hematological/biochemical laboratory parameters. [ Designated as safety issue: Yes ]
  

This phase II clinical trial is directed at evaluating the immunogenicity and the safety of the HIV-1 Tat protein-based vaccine. Anti-Tat antibody negative, HIV-1 positive subjects treated successfully with HAART will be screened and recruited for a 48-weeks study, including a period of 16 or 8 weeks treatment phase and a period of 32 or 40 weeks follow-up phase, in arm A or Arm B, respectively. One hundred twenty-eight subjects will be randomized 1:1:1:1 to one in 2 arms (Arm A and Arm B) and each arm will be divided in the following groups:

Arm A - Group I: 5 immunizations with Tat (7.5 microg) at weeks 0, 4, 8, 12, 16; Arm A - Group II: 5 immunizations with Tat (30 microg) at weeks 0, 4, 8, 12, 16; Arm B - Group I: 3 immunizations with Tat (7.5 microg) at weeks 0, 4, 8; Arm B - Group II: 3 immunizations with Tat (30 microg) at weeks 0, 4, 8.

Four vaccination regimens will be tested by intradermal administration of the Tat vaccine at two different doses (7.5 microg or 30 microg) in 5 or 3 immunizations.

Inclusion Criteria:

• Age 18-55 years
• Anti-Tat antibody negative subjects
• HIV-1 infected subjects under successful HAART treatment (with chronic suppressed HIV-1 infection) with CD4+ T cell counts > 400 cells/microliter determinated by 2 separate evaluations within the 3 weeks pre-study screening period (at day -21 and then between day -14 and -7)
• HIV plasma viremia < 50 copies/ml in the last 6 months prior to the screening and without a history of virological rebound
• Subjects with pre-HAART CD4 nadir > 250 cells/microliter
• Availability for the planned study duration
• Negative pregnancy test for women of childbearing potential (to be performed during the screening phase and just before the immunizations) and use of an acceptable mean of contraception (condom, hormonal or mechanical methods) for one month prior to immunization and for the all duration of the study
• Signed informed consent

Exclusion Criteria:

• History of AIDS-related opportunistic or neoplastic disease
• History of encephalopathy, neuropathy, or unstable CNS pathology (HIV or non-HIV related)
• History of non-HIV related neoplastic diseases, autoimmune diseases, severe and/or persistent angina or cardiac arrhythmias, or severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, thyroid gland or renal disease)
• Any evidence, as judged by the investigator, of unstable cardio-vascular disease (e.g. unstable hypertensive disease needing modification or introduction of an anti-hypertensive treatment)
• Laboratory findings exceeding the normal range adopted by each clinical site laboratory for haematology and biochemistry assessments will make undesirable for the subject the participation to the study. In particular, subjects presenting AST/ALT > 3 x the upper limit of normal will be excluded, as well as AST/ALT > 5 x the upper limit of normal in case of subjects having co-infections HIV/HCV related
• Chest radiography, within 6 months prior to study screening visit, showing evidence of active or acute cardiac or pulmonary disease
• History of anaphylaxis or serious adverse reactions to vaccines as well as serum IgE levels exceeding 1000 U.I./ml
• History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g. Steven-Johnson syndrome, bronchospasm, or hypotension)
• Early syphilis documented by Syphilis serology test [NOTE: if serology is documented to be a false positive or due to a remote (> 6 months), successfully treated infection, the subject is eligible]
• Active tuberculosis documented PPD skin test within one year [NOTE: if the PPD skin test is positive, then a chest x-ray will be done and if no findings consistent with active pulmonary tuberculosis and no indications exist for prophylaxis or treatment, the subject is eligible for participation in this trial]
• Medical or psychiatric condition which preclude subject compliance with the protocol. Specifically, persons with psychotic disorders, major affective disorders, suicidal ideation are to be excluded
• Current use of psychotropic drugs prescribed for major psychotic disorders;
• Use of any experimental HIV therapy or participation in another experimental protocol
• Current or prior therapy with immunomodulators or immunosuppressive drugs and anticoagulant drugs within 30 days prior to study medication administration;
• Concomitant treatment for HBV or HCV infections
• Live attenuated vaccines within 60 days of study inclusion [NOTE: Medically indicated sub-unit or killed vaccines (e.g., influenza, pneumococcal, hepatitis A and B) are not exclusionary, but should be given at least 4 weeks away from HIV immunizations]
• Receipt of blood products or immunoglobulin in the past year
• Previous participation in an HIV-1 vaccine trial
• Drug and/or alcohol abuse
• Pregnant or lactating women