Italy’s therapeutic AIDS vaccine shows drastic reduction of HIV virus reservoirs: study

ROME, FEB 13 — Clinical trials of an Italian therapeutic vaccine against AIDS showed a drastic reduction of virus reservoirs in treated patients, Italian researchers said on Wednesday.
The Tat vaccine was being developed by the AIDS Research Centre of Italy’s National Institute of Health (ISS), and the latest findings were published on “Frontiers in Immunology” scientific journal after an 8-year follow-up study.

It concerned 92 volunteers from the phase II of the research, who were monitored for 8 years after being firstly vaccinated.

“The administration of the Tat vaccine to patients on antiretroviral therapy (cART) proved able to drastically reduce the latent virus reservoir unassailable by cART alone,” the ISS said.
AIDS Research Center Director Barbara Ensoli further explained such results would open “new perspectives for a functional treatment of HIV, meaning a therapy able to control the virus even after suspension of antiretroviral drugs”.

“So far, the Tat vaccine has proved safe, immunogenic (induces the wanted immune system response) and most of all able to target the virus reservoirs, and to reduce the viral level there,” Ensoli told Xinhua.
“This latter function has never been observed before and, to the best of my knowledge, no other clinical tool has done this yet,” she stressed.

The new study was run in eight clinical centers in Italy, including San Raffaele and Sacco hospitals in Milan, S.M. Annunziata hospital in Florence, and University Policlinico in Bari.
The experimental vaccine targets a protein called HIV-1 Tat, which is known for playing a crucial role in the replication of the HIV virus causing the disease.

The vaccine would boost the response of the immune system to the protein, activating a stronger reaction compared to that triggered by antiretroviral drugs alone.

In fact, HIV could not be fully eliminated by cART drugs, since “the virus persists — without replicating — in some of the cells infected by pro-viral DNA”, ISS researchers said in a statement.
Scientists call this silent HIV form “latent virus reservoir” because it remains invisible to the immune system, and is not attacked by cART.

“The latent virus periodically reactivates and begins to replicate; therefore, interrupting the cART therapy inevitably leads to a restart of the infection, and this is why the therapy has to be followed throughout all life today,” they explained.

Yet, the latest findings showed patients treated with both antiretroviral drugs and Tat vaccine registered a strong decrease in pro-viral DNA levels in blood.
This reaction occurred “at an average speed 4 to 7 times higher than that observed in patients treated with cART therapy only during similar studies”, the ISS said.

Furthermore, the reduction of virus reservoirs in vaccinated patients was associated with an increase of CD4 cells and the CD4/CD8-T ratio (an indicator of strong immune system reaction), which were factors linked to low viral levels overall and to a good immune reaction, respectively.

This phenomenon sometime occurs in rare patients — called post-treatment controllers — who are spontaneously able to control the HIV replication after stopping the antiretroviral therapy.
As such, researchers believed the Tat vaccination might give patients “the ability to control the virus without taking medication, for periods of time that are yet to be evaluated through further clinical studies”.

“Valuable opportunities are emerging for the long-term clinical management of HIV, reducing toxicity associated with drugs, enhancing therapy adherence and, eventually, improving the people’s quality of life,” the AIDS Research Centre director stressed.
The study would proceed further, and the ISS has given no indication on when the vaccine might eventually be approved for the market.

The researchers’ goal in the next phase will be to test whether the suspension of the cART therapy in vaccinated volunteers was possible, and what effects it would bring about.
Yet, Ensoli told Xinhua such a new phase was yet to be scheduled for lack of funding.
So far, the Tat vaccine research cost some 26 million euros (29.3 million U.S. dollars) entirely provided by the Italian Health Ministry and Foreign Affairs Ministry, and overall involved some 350 patients through five trials (in Italy and in South Africa) – XINHUA