The Human Immunodeficiency Virus (HIV), the virus that causes AIDS, is one of the most pressing global health challenges of the past few decades. To date, 25 million people have died of AIDS since the first reported cases in 1981, with another 33.4 million living with HIV/AIDS. There is no known cure for HIV or AIDS and current treatment consists of a cocktail of antiretroviral drugs designed to keep the virus from replicating and propagating in the body. Resistance to these drugs, currently estimated at approximately 3.7 percent worldwide, has resulted in HIV virus mutations, new localized strains, and the need to develop more aggressive second-tier treatments.

Two new studies published this week represent both potential breakthroughs for effective HIV treatment as well as a new direction for experimentation in therapy and prevention. The first study, out of the University of Pennsylvania, utilizes gene therapy methodology to treat HIV patients with genetically modified T cells. These cells are infused with DNA coding for a retrovirus that recognizes the envelope protein of the HIV virus and kills any cells it encounters that contain the virus. Amazingly, all 43 patients treated with the T cells remain healthy over a decade later, with 41 showing strong populations of the cells remaining in their bodies fighting off HIV. A second University of California, Davis study harnessed a similar whole-scale immune approach, only they engineered stem cells with anti-HIV genes and then transplanted them into mice for immune replication and successful disease eradication.

In both of these studies, a novel approach uses the immune system’s precise and aggregate ability to seek out and destroy antigens, in this case cells containing HIV virus. One important difference is that the UPenn team used highly specific modified CD4+ T cells, the main target of the HIV replication machinery, as a subset of immune response in their human patients. The UC Davis team modified early-stage stem cells, giving rise to an eventual complete immune system of anti-HIV cells, even though only CD4+ populations were eventually measured in treated mice. This could be an important differentiation in studies going forward, because of notable worrying side effects of retroviral gene transfer into hematopoietic stem cells. T cells appear to be a safe immune cell population for gene transplantation. Nevertheless, immunological gene therapy presents a highly favorable plasticity in antigen recognition compared to antiretroviral pill therapy, which depends on consistent dose delivery, highly specific HIV gene recognition and the hope that in vivo HIV mutations would not occur or affect drug efficacy.

The impact of these limited clinical trials cannot be overstated on a scientific or socioeconomic level. Preventative HIV vaccine efforts have been largely frustrating, with the New England Journal of Medicine framing them as “one step forward, two steps back.” Merck’s most recent candidate was not only ineffective, but actually increased HIV susceptibility in patients. The principal aim of HIV vaccine development is the injection of an adenovirus type 5 vector to create an immune system capable of recognizing, and then killing, HIV the same way our bodies do measles or polio. But if genetic therapy successfully executes this approach after infection, it may render vaccine funding obsolete.

On a more grand medical scale, the impact of a one-time gene therapy treatment (with possible follow-ups after a decade in remission) for HIV is enormous. Even the one-a-day HIV drug cocktail, recently approved by the FDA, must be taken fastidiously and without pause for a lifetime. Other cocktails contain up to a dozen different pills, administered throughout the day. The side effects of HIV retroviral therapy, sometimes so severe that patients stop therapy, present a mixed blessing to HIV patients. The recent gene therapy trials, on the other hand, presented no adverse side effects in the (admittedly small) patient sampling, and 41 out of 43 patients had significant enough populations of anti-HIV CD4+ T cells to not necessitate further treatments. Even generic versions of current cocktail therapies cost $1,000 per year in countries like Brazil and India, a figure that is unsustainable in African countries, some of which are battling HIV/AIDS rates of greater than 15 percent.

Finally, the success of the aforementioned trials will resonate far beyond the HIV/AIDS community. For many years, pessimism and ethical debate about the ability of scientists to hone gene therapy methodology resounded in the biomedical community after several notable gene therapy trial deaths. While more wide-scale follow ups of the HIV study will surely need to occur, the astounding lack of even minor side effects in patients treated should buoy hopes for further funding and safer methodology. With several cancer studies showing similar results from T cell transplantation, the focus will naturally now turn to other disease types that might be combatted by such therapies, including arthritis.

Could we be looking at the inception of a medical miracle, thirty years in the making?