Recipients of the vaccine develop characteristics of spontaneous ‘post-treatment controllers’, whose immune system can control the reactivation of HIV after discontinuing therapy
— by the Italian National Institute of Health
A new study published in Frontiers in Immunology suggests that HIV infection could be controlled without the need for continuous lifelong antiretroviral medication. Administration of the Tat vaccine to people with HIV on antiretroviral therapy drastically reduced the drug-resistant ‘latent virus reservoir’, in a similar way to that seen in spontaneous ‘post-treatment controllers’ whose immune system can control the reactivation of HIV after discontinuing therapy. The Tat vaccine was developed at Italy’s National HIV/AIDS Research Center, under the leadership of its Director, Dr Barbara Ensoli.
“These results open new perspectives for a ‘functional’ cure of HIV, i.e. the ability to control the virus during the suspension of antiretroviral drugs,” says Dr Ensoli. “A functional cure would ease the long-term clinical management of people with HIV by reducing the cumulative toxicity of antiretroviral drugs while improving adherence to therapy and quality of life that are crucial especially for children and adolescents.”
Almost 40 years from the discovery of the virus, HIV/AIDS remains a global emergency. To date, almost 40 million people in the world live with HIV infection, half of them without any treatment, and international agencies are calling for a renewed effort, more investments and innovative strategies to find a cure for HIV and eradicate the virus.
Currently, strict adherence to lifelong therapy is required to control HIV, as a ‘reservoir’ of viral DNA invisible to the immune system and to antiretroviral therapy (ART) reactivates once therapy is interrupted. But according to Dr Ensoli, the results of the new study could change this.
The authors present data of the long-term clinical monitoring of 92 volunteers who completed the previous phase II clinical trial in Italy (ISS T002 ClinicalTrials.gov NCT00751595) and enrolled in the extended follow-up (ISS T-002 EF-UP, ClinicalTrials.gov NCT02118168). The 8-year study was conducted in 8 clinical sites in Italy: San Raffaele Hospital in Milan, L. Sacco Hospital of the University of Milan, San Gerardo Hospital in Monza, University Hospital of Ferrara, Policlinic Hospital of the University of Modena, Santa Maria Annunziata Hospital in Florence, San Gallicano Dermatological Institute in Rome, and the Policlinic Hospital in Bari.
The study shows that the volunteers vaccinated with Tat after being on ART for an average of 6 years, experienced, during the following 8 years, a continued decrease of viral DNA in blood, which occurred at an average speed 4-7 times greater than that observed in similar studies in patients treated with ART alone. Furthermore, in the vaccinated volunteers the reduction of the virus reservoir was associated with an increase in CD4+ T-cell number and CD4+/CD8+ T-cell ratio. A very small reservoir of latent virus (as evidenced by the low levels of proviral DNA in blood), and a good recovery of the immune system (as indicated by a high ratio of CD4+/CD8+ T lymphocytes) are found also in rare patients called ‘post-treatment controllers’, who can control the reactivation of HIV after discontinuing therapy.
“It is therefore conceivable that vaccination with Tat may confer to patients the ability to become post-treatment controllers, i.e. to control the virus without taking medications for periods of time,” concludes Dr Ensoli. “The duration of these periods will now be evaluated using controlled therapy interruptions in volunteers treated with ART and vaccinated with Tat.”
The economic impact of a functional cure for HIV is expected to be substantial. HIV is taking vast resources from the fight against poverty and inequality in the world: $ 563 billion between 2000 and 2015, a taxpayer contribution of $ 100 dollars in developing countries and $ 5,000 in Europe and North America ($ 330/$ year); and a net loss of national wealth (GDP) in African countries of between – $ 30 – $ 150 billion a year ($450 billion -4.5 trillion in 15 years), huge figures that impose urgent and innovative therapeutic solutions for HIV/AIDS.
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