Immunogenicity and Safety Trial of the HIV-1 Tat Vaccine

The study is a randomized, open label, phase II clinical trial directed at evaluating the immunogenicity (as a primary end-point) and the safety (as a secondary end-point), of the recombinant HIV-1 Tat vaccine in HIV-1 infected adult subjects, anti-Tat antibody negative, HAART-treated with chronic suppressed HIV-1 infection, CD4+ T cell counts \>= 200 cells/microliter, levels of plasma viremia \< 50 copies/ml in the last 6 months prior to the screening and without a history of virologic rebound. The immunogenicity of 3 or 5 immunizations of the two different vaccine doses (7.5 and 30 micrograms) of the Tat vaccine has been evaluated.

This phase II clinical trial was 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 have been 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 sixty-eight subjects have been randomized 1:1:1:1 to one of the 2 arms (Arm A and Arm B) and each arm has been 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 have been tested by intradermal administration of the Tat vaccine at two different doses (7.5 microg or 30 microg) in 5 or 3 immunizations.

Eligibility Criteria:
Inclusion Criteria:

* Age 18-55 years
* Anti-Tat antibody negative subjects
* HIV-1 infected subjects under successful HAART treatment with HIV plasma viremia \< 50 copies/ml in the last 6 months prior to the screening
* Subjects with any pre-HAART CD4 nadir;
* CD4+ T cell counts ≥ 200 cells/μl at enrolment;
* 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:

* Concomitant AIDS-related opportunistic disease;
* Concomitant neoplastic diseases;
* History of malignant neoplastic diseases \[NOTE: Subjects with history of non malignant neoplastic diseases completely resolved according to the fulfillment of all the specific recovery criteria, in agreement with the current guidelines in medical oncology are eligible\];
* History of encephalopathy, neuropathy or unstable CNS pathology, immunodeficiency, autoimmune disease, angina or cardiac arrhythmias, or any other clinically significant medical problems;
* 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);
* Chest radiography showing evidence of active or acute cardiac or pulmonary disease within 6 months prior to study screening visit;
* 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);
* 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;
* Concomitant participation in any experimental study;
* Current or prior therapy with immunomodulators or immunosuppressive drugs and anticoagulant drugs within 30 days prior to study medication administration;
* 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 (subjects who despite their participation as placebo in a HIV-1 vaccine trial have never been effectively administered with a HIV-1 vaccine are eligible);
* Drug and/or alcohol abuse;
* Use in the last 6 months or concomitant use of anti CCR5 inhibitors and/or integrase inhibitors and/or fusion inhibitors;
* Pregnant or lactating women