A team at the University of North Carolina School of medicine has shown a novel and innovative treatment method which might surpass the ones currently used in modern medicine, publishing the work on the online journal PloS Pathogens. Led by J. Victor Garcia, PhD, the team researched this new technique on humanized mice, rodents with an immune system composed of human cells, with persistent HIV.
HIV, or Human Immunodeficiency Virus, is classified as a lentivirus, or slowly replicating retrovirus in more general terms, transferred by bodily fluids. Compared to other retroviruses, it is quite a large structure, spherical in shape and approximately one sixtieth of the size of a single red blood cell.
The virus replicates in the immune system cells of the body, causing a progressive decrease in the efficiency of our immune system and allowing more opportunistic conditions to thrive.
Modern treatment for HIV is based on Antiretroviral Therapy (ART), a high successful lifesaving treatment which may allow people with the condition to live almost as long as a healthy individual. Various classes of ART drugs are used depending on the stage of HIV lifecycle, and thus have varying effects depending on how advanced the condition is; some prevent the virus from entering the cells, whilst others prevent an viral enzyme that allows copies of the virus to bud out of host cells. In doing so, ART decreases the amount of HIV in the body to quasi-undetectable levels, and the drugs have been the most effective treatment for HIV patients around the globe.
However, ART drugs are unable to eliminate the virus from body, meaning people with the condition need to follow a lifelong regimen while the virus still persists in their cells as a dormant or slowly multiplying entity, despite the medicine does enter human tissue. In addition, the use of ART may theoretically produce drug-resistant forms of the virus in the future, adding impetus to developing what is essentially a “cure.”
The new technique developed by the research team at the American university has shown it may be possible to achieve what the ART drugs have been unable to do: eliminate host cells contain the virus. This work is a continuation of previous research of HIV elimination, using a strategy whereby persistent viral components are exposed, via the activation of certain enzymes for example, which allows certain compounds to eliminate the virus.
The compounds used in Dr.Garcia’s work were immunotoxins – man-made proteins that are composed of a toxin linked to a target structure. The researchers used a bacterial toxin known as PE38 and linked it to the antibody 3B3 to form the protein, the latter serving as the target portion of the compound which may attach to host cells containing the virus.
They hypothesized the antibody is likely to bind to cells displaying the unique HIV antigen on the cell surface of the host, allowing the toxin to enter the cell via endocytosis, where a cell engulfs a molecule. Once the mice had been given the immunotoxin, as well as the traditional ART drugs, the scientists looked to see what affect it had on the number of cells showing HIV antigens. The results were particularly promising. While some persistent HIV ridden cells still remained, the researchers saw a six-fold decrease in the total number of immune system cells which contained the virus.
While complete elimination may yet to be achieved, Dr. Garcia and his team’s work have offered new perspectives and techniques when curing HIV, meaning future work and progress towards a potential cure seems to be looking promising.
How might HIV patients feel knowing a cure is closer?