HIV and Biotechnology: a perfect match

It’s the 1940s, and you’re venturing through the Guinean Forests of West Africa. The scorching heat coupled with the concern of contracting Malaria and Dengue Fever from mosquitoes is probably at the front of your mind. As food supplies run low, it seems like any source of food and water would help satisfy your insatiable hunger and thirst. However, unbeknownst to you, a deadly virus steadily spreads among certain mammals you might find appetizing. And, as reality would have it, as you and other wanderers consume animals like chimpanzees—the primary carriers of the Simian Immunodeficiency Virus (SIV)—the deadly virus mutates into the infamous Human Immunodeficiency Virus (HIV). Way to go!

HIV is a virus that severely reduces the function of our immune system and gradually makes us vulnerable to a wide variety of pathogens. Eventually, it progresses to become the dreaded Acquired Immunodeficiency Syndrome (AIDS). Prior to recent medical innovations, this incurable affliction had been synonymous to a death sentence. Over the decades following the 1940s, the virus spread across Africa and later into other parts of the world. Fast forward to the late 1970s and early 1980s, and rare types of pneumonia, cancer and other illnesses were being reported by physicians in Los Angeles and New York among a large number of homosexual men. These conditions were not present in people with healthy immune systems. For years, physicians were unable to find a successful cure to HIV, and this resulted in the loss of many lives, including famous celebrities like Freddie Mercury, the lead singer of Queen. 

What makes HIV so difficult to eliminate? It’s the way it integrates itself within our genetic material to the extent that it becomes one with our cells. More specifically, HIV is a retrovirus, belonging to a family of RNA viruses that insert their genetic material in the form of DNA into our cells so that they can successfully replicate and spread across our bodies. Since the end of the 20th century, scientists have tested and administered dozens of medications that have effectively reduced, but not completely eliminated, the viral load of HIV in humans. To elaborate upon the biomedical lingo, viral load is defined as the relative measurement of the amount of a virus in an organism’s bloodstream, typically measured in virus particles per milliliter. The treatments have shown some degree of promise by providing those with HIV with hope for much longer lives after diagnosis. 

But, even though scientists still haven’t found a complete cure, recent advances in biotechnology are on the verge of eradicating this sinister virus. In fact, in our very own region, the Miami Center For AIDS Research (CFAR), part of the Miller School of Medicine, functions as South Florida’s premiere center for HIV and AIDS research. Researchers at CFAR have recently focused on gene editing, a method of rewriting and throwing out infected genetic material so that the virus is suppressed to the point of nonexistence. One promising example of this is an AIDS vaccine that uses genetically engineered Herpesvirus. Just this year, scientists were able to achieve significant vaccine protection against AIDS in monkeys for the first time by administering several doses of the aforementioned vaccine over four months. Prior to this, only live, attenuated strains of SIV had been able to provide a similar degree of protection. 

The implications of the treatment don’t stop there. Although SIV is incredibly difficult to neutralize in Rhesus Macaques monkeys, similar to HIV in humans, researchers found that monkeys exposed to the vaccine were completely protected against repeated intravenous SIV exposure. This was primarily due to the modified herpesvirus vaccine, which was made from rhesus monkey rhadinovirus (RRV), eliciting a longer-lasting cellular immune response to different strains of SIV. When coupled with the genetically combined recombinant strain, both the replicating RRV and noninfectious SIV were produced. This resulted in a profound synergistic effect that was efficient enough to elicit a powerful response to fight off and completely eradicate the SIV infection. 

Although this treatment is promising, scientists continue to investigate other avenues for a possible cure. An alternative approach from researchers at CFAR revolves around the idea of providing long-term viral suppression, making the virus’ negative immune system impacts negligible. Using this method, a single injection of anti-HIV monoclonal antibodies—antibodies that are all made by the same type of immune cell—was able to completely suppress the virus for almost three years in one monkey and for extended periods in two others. Dr. Ronald C. Desrosiers, Professor of Pathology and a renowned HIV researcher at CFAR says, “[Our] ultimate goal is to deliver these potent broadly neutralizing antibodies so that the patient is safe for life.” 

However, in contrast to the prior study of herpesvirus as a vaccine, this antiretroviral drug therapy treatment is not a permanent cure. Unfortunately, removal of the antiviral drugs results in a rebound of plasma viral loads in the vast majority of individuals. Hence, repeated infusions are needed to maintain a noticeable protective concentration. In yet another new study, CFAR researchers used an adeno-associated virus (AAV) to deliver gene products into muscle cells, turning them into cellular “factories” that can produce the genetically engineered antibodies indefinitely. The results are astounding: after receiving a single injection of the AAV-delivered antibodies, the HIV viral load of one of the test monkeys dropped below the limit of detection, and has remained undetectable for more than three years. While the AAV delivery strategy did trigger a defensive immune system response that inactivated the antibodies in two other test monkeys, these subjects also maintained long-term viral suppression.

Ultimately, Dr. Desrosiers claims that his current study provides a proof of concept that this approach could potentially deliver a fully functional cure of HIV around the globe. “One advantage to this AAV approach is that it could be readily applied throughout the developing world, specifically third-world countries, where antiretroviral therapies are not readily available,” he states. While he feels confident that his methods can help address the global epidemic, he also harbors an understanding that only time can tell the direction of future treatments. But indeed, it seems that within the next decade, advances in biotechnology will provide researchers with the tools needed to finally initiate clinical human trials, thus truly marking the beginning of the end for HIV.