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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
     

Back Anti-Tat immunity in HIV infection

The immune response against Tat protein protects against HIV/AIDS progression.

The HIV-1 Tat protein is a regulatory protein produced early after viral infection that plays a key role in virus replication and expression, cell-to-cell viral transmission and HIV/AIDS progression. CNAIDS has thus undertaken studies to evaluate the effects of the host immune response against Tat. The results of these observational studies indicate that only a minority of HIV+ patients develops an anti-Tat immune response and that in these individuals disease progression is very slow. In particular, the presence of an anti-Tat humoral (antibody) response is associated to an asymptomatic state and clinical stability of the disease. Tat represents therefore an optimal target for the development of a vaccine against HIV that could counteract the progression towards AIDS.

CNAIDS conducted 4 observational studies in Italy and South Africa for a total of 738 HIV+ volunteers with the aim of collecting data on the frequency, intensity, quality and persistence of the anti-Tat immune response in both asymptomatic and antiretroviral (cART)-treated HIV+ subjects. The results of these studies indicate that anti-Tat antibodies, for reasons still to be determined, are detected only in a minority (15-25%) of HIV+ individuals, and that their presence is associated with a slower progression towards AIDS and a more effective response to therapy.
Further analyses of the following observational studies are ongoing to clarify the role of anti-Tat immunity and to identify other prognostic markers useful to the clinical and therapeutic management of HIV/AIDS:

  1. Longitudinal observational study to evaluate the impact of anti-Tat immunity in the progression of HIV infection under cART (ISS OBS T-002). This study was conducted in Italy on 128 cART-treated, virologically suppressed (i.e. with virus not measurable in blood) HIV+ adults, followed for 3 years
  2. Longitudinal observational study to evaluate the impact of anti-Tat immunity on the progression of HIV infection in asymptomatic, naïve-to-therapy HIV+ adults (ISS OBS T-003). This study was conducted in Italy on 61 participants that were monitored for 3 years
  3. Cross-sectional observational study aimed at evaluating the prevalence of anti-Tat antibodies in South African naïve-to-therapy or cART-treated HIV+ adults (ISS OBS T-004). The study was conducted on 531 volunteers (265 naive and 266 cART-treated) at the MEDUNSA Clinical Research Unit (MeCRU), in Gauteng, and the Walter Sisulu University HIV Vaccine Research Unit in Mthatha, Eastern Cape, South Africa
  4. Finally, a new longitudinal observational study is ongoing to identify the effects of the Tat protein and anti-Tat immune responses (induced by infection or Tat vaccination) in the formation and maintenance of HIV-1 reservoirs in the peripheral blood of cART-treated HIV-infected participants (ISS OBS T-005). The study is conducted in collaboration with the Istituti Fisioterapici Ospitalieri (IFO) - S. Gallicano Hospital, Rome, and foresees the enrolment of about 100 volunteers


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