BioWorld Today Correspondent

LONDON – A Phase II trial in Italy of a therapeutic vaccine for HIV has delivered encouraging interim results. The study, which involved giving a vaccine made from recombinant biologically active Tat protein, has been expanded to recruit more participants.

Barbara Ensoli, director of the National AIDS Centre at the Istituto Superiore di Sanità, of Rome, told BioWorld Today: "The first results of this open-label Phase II trial have indicated that we may be able to improve the treatment of HIV using this approach."

She emphasised that the work is still in the research phase and that much time and investment is still required in order to work toward an approved, commercial vaccine. "Nevertheless," she added, "this is the first time, to my knowledge, that any therapeutic vaccine in the HIV field has been shown to have any type of efficacy."

One important implication from the study, she said, is that researchers developing preventative vaccines for use in uninfected people will want to consider what role the immune response to the Tat protein might play and how they could stimulate this type of response. A much larger, placebo-controlled therapeutic trial of the vaccine in South Africa is also being organized, Ensoli said.

An account of the current study appeared in PLoS ONE: "Therapeutic Immunization with HIV-1 Tat Reduces Immune Activation and Loss of Regulatory T-Cells and Improves Immune Function in Subjects on HAART."

Enrico Garaci, president of the Instituto Superiore di Sanità, said: "The results published . . . in PLoS ONE demonstrate that it was worth it to pursue the Tat vaccine strategy. The improvement of the immunological parameters upon vaccination of patients being treated with antiretroviral drugs represents a key milestone."

Ensoli and her colleagues are now looking for partners to help them progress work on the candidate vaccine.

Recruitment for the study, being conducted by a consortium of researchers and clinicians at 11 centers throughout Italy, is still ongoing. The original design of the investigation was to recruit 128 HIV-positive patients who were taking highly active antiretroviral therapy (HAART).

These patients are being allocated at random, to receive one of two doses (7.5 mcg or 30 mcg) and one of two dosage schedules (three or five immunizations). The vaccine is given intradermally, without adjuvant, based on the data from previous monkey and Phase I studies.

To evaluate the effect of the vaccine, the researchers are comparing data from the trial participants with a cohort of patients in a prospective and parallel observational study that began before the trial and will last for five years.

Because the trial is open label, the researchers could see early on, when only 87 patients had been recruited, that the vaccinated individuals appeared to be responding well to the Tat vaccine, Ensoli said.

She said the vaccine-treated patients showed statistically significant (p < 0.05) improvements in several important parameters commonly used to assess the efficacy of HAART. For example, these patients had significant increases in numbers of CD4+ T cells and B cells, significant reductions in CD8+ T cells and other significant improvements in immune system function, compared to baseline data. When the researchers compared these interim results to those from a group of 32 HIV-infected patients with comparable baseline characteristics who were taking HAART but had not been vaccinated, they found that the nonvaccinated patients did not show the same improvements in CD4+ or B cell counts, or the overall benefit to immune system homoeostasis, that the vaccinated patients had shown.

Further analysis also demonstrated that the Tat vaccine was safe, and that it could induce specific and durable antibody and cellular immune responses. The interim results also suggested that the patients who were most immunocompromised may benefit most from Tat vaccination.

Following discussion with the appropriate regulatory authorities in Italy, Ensoli noted, the trial design has been amended to recruit 160 patients in total. It will also now recruit individuals who are more immunocompromised.

Additional follow-up of those who have received the vaccine will determine whether there is a need to give booster inoculations and, if so, at what intervals. "We are also discussing possible studies of controlled interruption of HAART therapy, to see if this therapeutic vaccination can offer patients a respite from treatment for periods of time," Ensoli said.