A drug that used to be administered to individuals with HIV/AIDS, which has long been replaced with newer, novel antiretroviral therapies, has been rediscovered by scientists who used this drug to gain insight into the human body's natural ability to use its immune system to fight the virus. The study, published in this month's journal PNAS, could pave the way to find new targets for drugs.

The first clinical evaluation of the way in which the drug, called interferon, fights infection in people, was introduced by a team of U.S. and Swiss researchers who were led by scientists at the University of California in San Francisco (UCSF). The biotechnological drug interferon is based on a naturally produced protein that fights infection.

During the early phases of the HIV/AIDS epidemic, people received purified interferon to alleviate several of the disease's symptoms, however, the way in which the drug functions always remained a secret.

Leading researcher, Satish K. Pillai, PhD, assistant professor of Medicine at UCSF and the San Francisco VA Medical Center says:

Even though lab tests have shed light on how interferon may function to inhibit HIV in vitro during the past few years, until now there has been no clinical evidence of how the drug targets HIV in those who received treatment, as very few people still take the drug for HIV. Interferon is still administered in combination with other medicines to treat hepatitis C. This enabled the team to evaluate the drug's effect on HIV.

Pillai and his team recruited 20 people with both HIV and hepatitis C from the Swiss HIV Cohort Study that started in 1988. The researchers were able to assess how interferon works to inhibit the virus as all participants took interferon to treat hepatitis C, but none took antiretroviral drugs to treat HIV.

The study enabled the team to gain further insight into the immunity system's fairly obscure components, known as restriction factors that consist of naturally produced chemicals to control viruses, such as HIV and prevent them from infecting other cells.

These are just two aspects of the overall fight between HIV and the body's immune system. It is a fight whereby the immune system attempts to kill the virus, whilst the virus incessantly counter-fights by attacking the immune system.

In other parts of the immune system, entire cells eat up invading pathogens or attack other cells, however, in HIV the restriction factors' actions are more subtle and sophisticated and located within the infected cell itself.

This explains why scientists until recent years only had a limited understanding. One restriction factor, the APOBEC3 protein, targets viruses by secretly jumping onto new virus particles as they form. By doing this, the APOBEC3 protein violates HIV's genetic material through mutation so when the virus tries to infect another cell, it is no longer able to replicate. The approach of Tetherin, another restriction factor, is much more direct.

It connects to virus particles as they surface from the body's infected cells and literally ties them in place, and therefore disables them from moving to other locations within the body where they could infect new cells. However, HIV has its own weapons to counter-fight these attacks. HIV produces a protein, called Vpu, which neutralizes tetherin whilst another HIV protein called Vif, which destroys APOBEC completely.

Pillai and his team demonstrated in their new study that interferon fights HIV by negotiating both restriction factors' actions. The team used samples from the 20 participants and measured APOBEC3 and tetherin levels before, during and after they took interferon. They observed that the levels increased in response to interferon being in the bloodstream. During interferon therapy those participants who had the highest restriction factor levels displayed the most dramatic decrease in HIV viral load.

Pillai declares that even though they have gained a new understanding into HIV, the knowledge does not imply that new drugs or new therapies will soon become available for treating those infected HIV, however, he remains optimistic that scientists may figure out a way in the future of how to improve this defense mechanism and in particular how to improve the expression of restriction factors like tetherin and APOBEC3 in HIV-1 infected individuals.

If these factors can be brought forth to higher levels, their attack on the virus may have a stronger impact and can possibly even override any HIV counter-attacks and help in erasing the virus from infected cells.