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
     

Experimental therapies for cervical cancer

How antiretroviral drugs could be used to treat cervical cancer 

Cervical cancer (CC) represents one of the main causes of morbidity and mortality in women worldwide, particularly in human papillomavirus (HPV) and human immunodeficiency virus (HIV) doubly infected women. CNAIDS is committed to developing new treatments to block CC onset and progression.

Despite the introduction of mass prevention screening, invasive CC is the 4th most frequent cancer in women worldwide and the 2nd in Africa, representing an important cause of morbidity and mortality. The risk of CC development is greatly increased by the persistent infection of cervical epithelial cells with the high-risk oncogenic papillomavirus (HR-HPV), the causative agent of CC. Of note, a significant fraction of CC is caused by HR-HPV types not targeted by current HPV vaccines, and dysplastic cervical lesions (CIN) can progress to invasive CC despite surgical intervention. Therefore, CIN/CC therapy could greatly benefit from targeted pharmacological interventions.
CIN incidence and aggressiveness are particularly dramatic in HIV/HPV co-infected women. In HIV+ patients, however, new combined antiretroviral therapies (cART) have reduced the appearance of CIN lesions or their progression in CC.
CNAIDS is committed to investigating the activity of antiretroviral drugs belonging to the HIV protease inhibitor (HIV-PI) class, which exert direct anti-angiogenic and anti- tumoral effects against various tumors, in the prevention of CC onset and progression. To this purpose, in collaboration with the IRCCS Istituto di Candiolo - FPO, we used the "transgenic" mice model expressing the HPV E6/E7 onco-proteins, which develop CIN/CC lesions. In this model, CIN progression occurs by activating an "angiogenic switch" that leads to progression into invasive cancer, thus allowing the study of HIV-PI activity in cervical lesions. CNAIDS is also involved in studies using HR-HPV-infected CIN/CC cell cultures "in vitro". These studies will allow to evaluate HIV-PI activity on key parameters of CIN/CC cells, such as proliferation, survival, invasion of surrounding tissues and differentiation. Our in-vivo and in-vitro results indicate that HIV-PI inhibit the activity and expression of extracellular matrix metalloprotease (MMP)-9, an enzyme responsible for "remodeling" the non-cellular component present in all tissues (the extracellular matrix), which has a key role in CIN development and progression into CC. 
This project will therefore help to clarify HIV-PI effects on CIN/CC development and progression independently of HIV infection, and to develop new therapies to prevent or treat tumors that arise in both HIV+ and seronegative patients.