This is a headache-giving job: finding a cure against HIV. Now, a new research made at the University of Florida has revealed the way HIV changes over the course of a person's lifetime into a more lethal form that leads to the onset of full-blown AIDS and new therapeutic agents could target the virus earlier during its development.

"We were very interested in understanding how the virus mutates from the beginning of the infection until the end. Previously, the only thing known was that somehow the HIV population mutates. And as soon as that happens, patients start developing AIDS. But no one knew how and where the population evolved over time," said lead author Marco Salemi, an assistant professor of pathology, immunology and laboratory medicine in the UF College of Medicine.

The UF team monitored four children born with HIV, investigating blood samples and tissue samples at birth, throughout life and just after death. A high-resolution computational technique tracked mutations in a protein enabling HIV to bind to human cells and assigned the virus into two groups, R5 and X4.

The R5 population is predominant during the infection's early stages, while the X4 population appears later, just before the full-blown AIDS installs.

"The general dogma has always been that the X4 viruses are more pathogenic than the R5 viruses. And that really isn't true. People die from the R5 viruses. But certainly evolution of these X4 viruses is not a good prognostic indicator. So if we could understand the selective pressures that push viruses to develop like that, and the steps involved in the conversion of viruses, then we might be able to set up new targets for drug development." said senior author Maureen Goodenow, AIDS researcher in the UF College of Medicine.

Other researches were made on cell culture or animal models to investigate the virus over time, but this is one of the first studies following the progression of HIV in human patients. The UF team found that most viral changes occur in the thymus, a gland situated behind the breastbone and controlling the immune cell development in children.

"We found that the late-stage viruses, the X4 viruses, were localized predominantly in the thymus. It says that the thymus is the place where these viruses develop, or at least where they're localized and replicate." said Goodenow.
The UF team shows that the X4 viruses are not present in the whole body, but rather they evolve directly from the R5 population before the onset of AIDS. HIV had a similar way in each child, no matter the variations in the subjects' medical histories.

"We're starting to see what looks like a program of virus development over time. And it doesn't matter who the person is. And it doesn't matter what the time scale is. It's raising the possibility that, in fact, the evolutionary track of the virus is not totally random. There could be a real developmental program that the virus goes through." said Goodenow.

8 years ago, when the research started, pregnant women infected with HIV had less therapeutic options, while recent drugs can decrease the levels of mother-to-child transmission to less than 2 %. Without medication, about 40 % of infected mothers would transmit HIV to their babies. The new therapies came too late for the children registered in the research, they all developed full-blown AIDS by their first birthdays.

"Their whole virus infection was what we call the natural history. This tells you what happens in the absence of combination antiretroviral therapy. The next step will be to track the evolution of HIV in adults before and after treatment. The researchers hope their findings will pave the way for new drugs that interfere with the virus' ability to evolve in the thymus." said Goodenow.