A long-term cure for HIV in the offing?

A short biographical sketch of IM Luca Shytaj

His name is Iart Luca Shytaj, and he was born in Albania (Tirana) in 1986. His parents moved to Italy when he was six years old and he became an Italian citizen, with dual Italian-Albanian citizenship, in 2007. Luca (as he is known to friends) is an International Chess Master and has one GM norm, earned in the Tromso Open 2009. He represented Albania twice in Olympiads (Calvia 2004 and Turin 2006) and Italy once in an Olympiad (Dresden 2008 – the picture above, by Cathy Rogers, was taken there) and once in a European Team Championship (Novi Sad 2009). He won the Albanian Championship (2003) and the Italian Rapid Championship (2009). His highest rating ever was 2507 (current rating 2456).

In the scientific field Luca holds a master degree in Genetics and Molecular Biology (from the “La Sapienza” University in Rome; his bachelor degree, from the same University, is in general Biology). Currently he is doing a PhD in Medicine (the full name of the course is “Medical Microbiology, Immunology and Infectious Diseases”). He performs his research both at the Italian Institute of Health in Rome and in the United States (Maryland) at Bioqual Inc. (a company collaborating with the Institute of Health).

IM Luca Shytaj (picture above in the Maryland medical research laboratory)

Luca Shytaj is the first author of both the articles in which the authors show the results of their novel therapy. He has also presented this work in several scientific conferences (Fifth International Workshop on HIV Persistence During Therapy, Sint Maarten, West Indies 2011; Towards and HIV Cure, International AIDS Society’s Pre-Conference Symposium Washington DC, USA; HIV DART, San Diego, California, USA 2012). Luca kindly sent us the following summary of his scientific work.

Background of the research

1. AIDS, caused by human immunodeficiency virus (HIV), is a major disease of mankind, having already caused more than 30 million deaths since its outbreak in the early 80’s and currently affecting ≈34 million people worldwide.

2. At the present time, the most successful treatment available for HIV infection is antiretroviral therapy (ART; usually in the form of a combination of at least three drugs). Antiretroviral therapy can stop viral replication and thus prevent the progression of HIV infection to AIDS.

3. Antiretroviral therapy, however, cannot completely eliminate the virus from the infected individual. As soon as the therapy is suspended the virus quickly takes over again, recreating the pre-therapy scenario.

4. Thus, antiretroviral therapy binds the patient to lifelong therapy adherence. This results in several problems such as drug toxicities, drug resistance (that may render the treatment ineffective) and a decreased life expectancy.

5. Even the sub-optimal scenario of antiretroviral treatment is not accessible to the majority of HIV infected people since they live in low/very low income countries (most of the HIV infect population lives in sub-saharian Africa) and cannot afford the very high cost of antiretroviral drugs (usually >15,000 US$ per year per patient). Also in high income countries (for example US), the poorest sections of the population are often unable to meet the expenses required for treatment. In the countries in which these expenses are covered by the government, they represent a significant burden for the health sector.

6. Moreover, the absence of a cure for HIV results in the persistence of a widespread stigma towards the infected population.

Our research goals and results

1. Our research project is aimed at finding a cure for HIV/AIDS that should allow the patients to either get rid of the virus completely (this is called “sterilizing cure” in the medical community), or to autonomously control the virus without showing disease symptoms and without the need for lifelong drug assumption (this is called “functional cure”).

2. The research is funded by the Italian Institute of Health (based in Rome) and is carried on with the collaboration of several universities and private companies both in Italy and in the US. The “core” research group is the one at the Italian Institute of Health, and the project director is Dr. Andrea Savarino (MD), my PhD thesis advisor.

3. Our work is conducted on monkeys (more precisely, on macaques). The macaques are infected with a virus that is closely related to HIV (it’s called SIV, “S” stands for simian). This virus causes AIDS like the human virus, but it is more aggressive and thus macaques usually develop the symptoms of AIDS earlier than humans.

4. Our most important result so far has been the achievement of a functional cure (see point 1) in macaques. We achieved this result by using a combination of antiretroviral therapy (the standard baseline therapy for HIV infected patients) and two experimental drugs: auranofin and buthionine sulfoximine.

5. Our drug combination is administered only once and only for three months. After these three months the therapy is stopped and the macaques are able to control the virus independently without showing signs of disease progression.

6. The rationale of our therapy is to induce a safe and gradual replacement of the "diseased" white blood cells (that are the cells infected with the virus) with fresh and efficient cells. Moreover, our therapy is able to boost a specific branch of the immune system and, as a consequence, the immune system can control the virus after the therapy is stopped. The virus is still present in the organism, but it is kept constantly under check and thus is unable to cause AIDS.

7. The main advantage of our therapy over the current situation is that it spans for three months instead of the whole life of the patient. This may allow to provide a globally scalable curing strategy.

8. The main advantages of our therapy over other proposed curing solutions are that:
   • We tested our therapy in the “late” phase of the disease (in medical terms, the “chronic phase”). The great majority of the infected population is revealed to be HIV positive in the chronic phase. Other strategies have obtained good results in the “early” phase (“acute” phase) in which the virus is less widespread and thus easier to target. Unfortunately only a very small minority of the patients is detected to be HIV positive during the early phase and thus successful treatments during this phase have no real impact on a global or even national scale.
   • Our therapy proved to be safe on macaques and relatively easy to administer. Moreover, the individual components of our drug combination have good safety profiles on humans. The only other therapies that have been successful in the chronic phase of the disease (one of them, performed in Berlin, achieved the complete elimination of the virus in the patient) require life threatening procedures such as aggressive chemotherapy followed by stem-cell transplants and thus their use has been restricted only to patients that have not only HIV but also advanced cancer.
      

9. The results that I mentioned have been published in two articles on two major peer-reviewed journals: Shytaj et al. PLOS Pathogens 2012 and Shytaj et al. Retrovirology 2013.

10. The results have been cited by non-specialized media both in Italy (for example in the main national newscast TG1 or in major newspapers such as “La Stampa”) and abroad (for example in the San Francisco Chronicle).