TOPIC

Infectious diseases, HIV

HIV/AIDS

The Italian National Institute of Health (ISS) is at the forefront in the fight against infectious agents which, constantly changing over time, make it necessary the frequent updating  of priority actions.

The ISS implements surveillance, prevention and control measures against emerging diseases such as those deriving from the spread of antibiotic-resistant biological agents commonly found in hospital environment, and those transmitted by vectors, such as chikungunya, dengue and West Nile.

Vaccine preventable diseases, although they have been reduced due to effective interventions, represent a significant burden of diseases which require to maintain a high level of attention.

Viral hepatitis and sexually transmitted infections, as human papillomavirus (HPV) infection, are a paradigmatic example of how chronic infections can result in degenerative diseases and even cancers. A vaccine is available for hepatitis B virus (HBV) and HPV infection.

Infectious diseases include also neglected tropical diseases, as intestinal parasitosis and echinococcosis, found in many parts of the world.

With regard to HIV / AIDS, the antiretroviral therapy (ART), although it has saved millions of lives, does not eliminate the HIV from the body nor restore the immune system completely back to normal. Furthermore, it has limited effects if started late or not taken regularly.

In order to stop the HIV epidemic and assure those living with the infection (about 38 million people with HIV / AIDS in the world, including 20.6 million in Africa) better quality of life and life expectancy, the ISS develops surveillance, prevention and treatment strategies, working in cooperation with the National Health Service (SSN), Regions, developing countries and international bodies.

General aims of ISS research activities on HIV/AIDS include:

  • study and surveillance of the spread of HIV and its variants, and of co-infections in general and vulnerable populations
  • study of the mechanisms of infection, of development of AIDS and associated diseases
  • facilitating ART adherence by improving its effectiveness and reducing its side effects
  • development of new strategies capable of preventing infection, reducing its progression and enhancing the effectiveness of ART, in particular preventive and therapeutic vaccines
     

ISS at the forefront in South Africa against HIV/AIDS

An extensive HIV program conducted jointly by the National HIV/AIDS Research Center and the South African Department of Health.

The project, funded for 20 million euros by the Italian Ministry of Foreign Affairs and International Cooperation (MAECI), was conducted by the National Centre for HIV/AIDS Research (CNAIDS) in close cooperation with the Department of Health of South Africa (NDOH) and the South African Medical Research Council (SAMRC).

The program, in support of the South African Department of Health's national plan to implement a global response to HIV/AIDS, has been conducted along three lines: the Service Component, aimed at capacitating and strengthening HIV/AIDS care and clinical research in the public sector in three provinces of South Africa; the Production Component, aimed at establishing a GMP ("Good Manufacturing Practice") facility for vaccine production in South Africa; the Vaccine Component, aimed at conducting a phase II clinical trial with the Tat vaccine against HIV/AIDS developed at CNAIDS. The program, conducted in close cooperation with South African counterparts, began in 2008 and has recently ended with activities aimed at ensuring the sustainability of the results through the "Tat Vaccine Partnership", an initiative aiming to mobilize public and private resources in Italy and South Africa to complete the testing of the Tat vaccine (i.e., phase III efficacy testing). The impact of the program has been positively evaluated by the United Nation Industrial Development Organization (UNIDO), which pled for mobilization of resources toward completion of vaccine testing.

Through the program, ISS and CNAIDS have built enduring operational and collaborative links with NDOH, the provincial "Department of Health", SAMRC and local communities in the provinces of Gauteng (Health District "Tswane 1"), in Eastern Cape (Health District "OR Thambo"), in Mpumalanga (Health Districts "Ehlanzeni", "Gert Sibande" and "Nkangala") and in Kwazulu Natal (KZN) (Health District "Umzinyathi"). Program intervention in the public health sector was aimed at the provision of equipment to strengthen basic clinical care and to promote the achievement of National Core Standards, strengthening clinical and laboratory data capture and analysis, and training of human resources (both medical and paramedical staff).

Further, the implementers have established a clinical and laboratory platform for conducting clinical research in the public sector in South Africa. Through the development of the Clinical Research Units "Mecru" and Walter Sisulu University HIV Vaccine Research Unit (WSUHVRU) (now Nelson Mandela Academic Clinical Research Unit), based in the public universities "Sefako Makgatho" (Pretoria area, Gauteng) and "Walter Sisulu" (Mthatha area, Eastern Cape), the platform is able to integrate clinical research with HIV patients recruitment, care and surveillance at rural or sub-metropolitan public health clinics. The platform also integrates public diagnostic laboratories of the National Health Laboratory Service and the research laboratories of the Clinical Research Units and ISS-CNAIDS. This operational network has also interfaced with some advanced Clinical Research Units in the Johannesburg and Soweto area (HIV Clinical Research Unit and Perinatal HIV Research Unit).

Through the program, a GMP facility for the manufacturing of recombinant vaccines was established at "BIOVAC", a South African public/private biotech company in the Cape Town area. Finally, the phase II trial of the Tat vaccine was completed, followed by a follow-up study for the evaluation of the persistence of the immuno-virological effects Tat vaccination. The results of the randomized, double-blinded and placebo controlled trial with the Tat vaccine, conducted in patients on antiretroviral therapy, showed the induction of persisting anti-Tat antibodies reactive against the Tat protein from different virus strains, which was associated with a significant increase in the number of CD4+ T lymphocytes in vaccinated subjects as compared to placebo.

The results of the studies conducted in Italy and South Africa indicate that the clinical development of the Tat vaccine should be continued with efficacy studies (phase III of the trial) toward vaccine registration. These studies will test the use of the vaccine in patients who respond poorly or are not adhering to the therapy, and will to evaluate its use in the pediatric population and in patients at the first diagnosis of infection (Test&Treat).