Written by: Erin Yoo

Seventy million people suffered and are suffering through it (World Health Organization, n.d.a.). Thirty-three million people died from it (World Health Organization, n.d.a). In the U.S., about four hundred new cases emerged out of every thousand people every year from 2000-2015 (World Health Organization, n.d.d). HIV/AIDS has been the source of countless deaths, pain, trauma, and grief for millions of people around the world. As a result, there has been much effort in the scientific community to research, develop treatments, and fight the virus and its ensuing health problems. Fortunately, one such advancement was made in August 2020 with the research and news of a patient who seemingly beat HIV, without any medical help (Saey, 2020).

What is HIV?

HIV is an acronym that stands for “human immunodeficiency virus” (also seen in green in Figure 1). In brief, this virus weakens the immune system to the point of tremendous vulnerability to diseases—diseases that normally wouldn’t cause serious pain or damage to the typical healthy human body (HIV.gov, 2020). HIV does this by taking over white blood cells called CD4 cells and using the cell bodies and resources to generate new viruses (World Health Organization, n.d.b). This relies on HIV genetic material becoming integrated into cell DNA as most virus survival does; Once the cell reproduces, the code for virus production also reproduces throughout the body, spreading quickly. This gradually degrades the immune system, and patients will often become victims to other diseases such as tuberculosis, lymphoma, and cryptococcal meningitis which may end up taking their life (World Health Organization, n.d.b).

Initial symptoms of HIV are often comparable to influenza’s symptoms including a fever, rash, headache, sore throat, so many people do not realize they have been infected with HIV in the first few months (World Health Organization, n.d.b). Moreover, this initial period is also the most infectious period, so many unknowing people may spread the virus to others through sexual intercourse, sharing drug injection needles, or from a pregnant mother to her fetus (HIV.gov, 2020; World Health Organization, n.d.b). Symptoms also worsen with time, growing to include swollen lymph nodes, weight loss, and diarrhea (World Health Organization, n.d.b). After a certain point, especially if untreated, HIV patients will develop AIDS, which stands for “acquired immunodeficiency syndrome” (HIV.gov, 2020). This signifies a severely weakened, compromised immune system and the final stage of HIV infection. Life expectancy for those with AIDS and not taking medication is three years (HIV.gov, 2020). Positively, however, many patients today will not develop AIDS because HIV medication is widely accessible (HIV.gov, 2020). This type of medication is known as antiretroviral therapy/treatment, or ART, and can stop the progression and even spread of HIV infection (HIV.gov, 2020). Currently, about 99.5% of HIV patients around the world use ART (Saey, 2020).

Figure 1

Image of HIV (green) on a human cell (purple).

Source: Science News

Elite Controllers

Though HIV infection is infamous for being chronic and everlasting without a cure, one patient, known as patient EC2, has eliminated the virus wholly on their own (Saey, 2020). Scientists analyzed 1.5 billion of patient EC2’s cells and not one indicated the presence of a functioning virus*, even though the patient had not received any medical treatment or care (Saey, 2020). The phenomenon of a HIV-free body in an HIV patient has only previously happened two times. Both cases included bone marrow transplants, however, so those patients did receive external help (Saey, 2020). In a different analysis of over one billion cells of a different patient who didn’t receive medical treatment or outside help, patient EC1, only one functioning copy of the virus was found (Saey, 2020).

*Nonfunctioning copies of the virus were found.

These types of patients are categorized as “elite controllers,” or HIV patients that have been able to sweep their body of the deadly virus, effectively curing themselves without medical treatment. More officially, they are defined as people that have undetectable levels of the virus without medicine or antiviral drugs long-term. About 0.5% of those with HIV are elite controllers (Cairns, 2020). These patients barely experience any symptoms or damage of HIV/AIDS, if at all (Saey, 2020). Scientists hope that by researching these patients and the mechanisms their bodies use to beat HIV, they can develop better, more effective treatments and drugs for the disease afflicting so many (Saey, 2020).

In examining the immune cells and genome of elite controllers, scientists discovered that much of their HIV genetic material was stored in atypical parts of the cell (Cairns, 2020; Saey, 2020). Normally, HIV will become embedded directly into or near a cell’s genome after being led there by “guiding proteins” (Saey, 2020). In contrast, copies of the virus were found in “gene-poor” areas of the genome, known as heterochromatin, and prevented from being expressed by cellular guards in elite controllers (Saey, 2020). In this way, the virus was largely inactive and nonthreatening (Saey, 2020).

One proposed hypothesis for this is that elite controller immune systems destroy cells with functioning copies of the virus in cell DNA, not including cells with inoperative viruses in heterochromatin (Saey, 2020). The next step for science would be to figure out exactly how the immune system targets and destroys the normal infected cells, because that mechanism isn’t known or understood yet (Saey, 2020). Figuring out this process could lead to greater developments in the pursuit of HIV/AIDS treatment, curing millions across the globe.

Natural Immunity

There are also some people who are naturally immune or greatly resistant to HIV and thus can’t be infected with it. This differs from elite controllers who are, or have been, infected with HIV but have the ability to naturally fight the virus off. Most people with this natural immunity have European ancestry, particularly Swedish ancestry, which has led some scientists to believe the immunity originated from the Vikings and spread through the Viking invasions (Paoli, 2013). The immunity is a result of the CCR5-delta 32 mutation, and carriers need to have two copies of the mutation in order for it to have effect (Paoli, 2013).

The reason this mutation works is that it reduces the size of cell receptors on the outside of immune cells, specifically the CCR5 co-receptor (Paoli, 2013). These cell receptors are needed in order for the virus to break into a cell and take over its machinery to reproduce; If the virus can’t attach itself to the receptors, immune cells will not become infected (Paoli, 2013). Interestingly, this mutation seems to have existed long before the first human contraction of HIV (Paoli, 2013). Some believe the mutation has helped protect people against other diseases throughout history such as smallpox or the bubonic plague* which is why it was passed down for so long (Paoli, 2013). However, it should be noted that carrying two copies of the mutation does not guarantee immunity to HIV since there have been cases of infected patients that carried both copies of the mutation.

*Smallpox seems the more likely story because it is viral—the bubonic plague is bacterial—and has stayed in humanity for hundreds of years causing millions and millions of deaths. The smallpox virus also depends on CCR5 receptors to invade immune cells (Paoli, 2013; University Of Liverpool, 2005).

Other Treatment Methods

Of course, the pursuit of HIV/AIDS treatments and research doesn’t stop there. Scientists have developed multiple ways of treating HIV patients, allowing many to live a normal life. In fact, daily ART pills are the way most patients have survived. In 2019, of the thirty-eight million people who had HIV/AIDS, 68% had access to ART (World Health Organization, n.d.b).

Another somewhat recent solution is inhibition drugs injections. In order for new copies of HIV to become infectious and spread to other cells, it has to mature. Part of this maturation process includes reassembly of the virus itself, which requires the virus to cut certain connection points in order to repiece different parts (European Molecular Biology Laboratory, 2016). One such cutting point includes the connection of the capsid protein and spacer peptide 1 (European Molecular Biology Laboratory, 2016). In an immature virus, this connection point is hidden from the cutting mechanism. The virus has to change its structure to expose the connection point and cut it. The inhibition drug takes advantage of this fact by preventing the immature virus from changing shape, preventing the cutting of that point and the maturation and spread of HIV (European Molecular Biology Laboratory, 2016).

An additional solution is the mechanism of binding antibodies to immune cell receptors, blocking it off from the virus (Scripps Research Institute, 2017). This is more effective than the traditional method of letting antibodies float in the bloodstream to find immune cells. One trial of experimenting with this method showed how the immune cells then became resistant in the long-term to HIV with the antibodies tied to them (Scripps Research Institute, 2017). Those newly resistant cells were then able to quickly replace dead immune cells (Scripps Research Institute, 2017). Through this method, reliance on other HIV medications, such as daily pills which can be a nuisance, could become unnecessary. Furthermore, those who are taking HIV medication could become resistant to the virus, becoming “post-treatment controllers.” However, research and evidence for this is not sufficient for it to be considered a proven fact (Cairns, 2020).

Conclusion

The research and discovery of elite controllers holds important significance for the world and human health. Amid a pandemic that threatens even the healthiest populations, those with preexisting medical conditions and/or are immunocompromised, such as HIV and AIDS patients, face an unimaginable amount of scary possibilities for their wellbeing and future. With the discovery of Patient EC2, scientists and the public now know it is possible for the human body to eliminate HIV on its own. Figuring out and implementing the mechanisms of this lifesaving anomaly could perhaps one day provide a cure for a disease that millions died from and that millions are dealing with today. Improving treatments like drug injections and oral medications will continue to provide opportunities for patients to live longer, happier, and healthier lives. Meanwhile, research on the workings of natural immunity, not to mention the possible “post-treatment controllers,” allow us to hope for a future in which HIV and AIDS are completely eradicated.

References and Sources

Bernstein, L. (2021, January 22). FDA approves breakthrough injectable HIV medication. Microsoft News. https://www.msn.com/en-us/news/us/fda-approves-breakthrough-injectable-hiv-medication/ar-BB1d0MKj

Cairns, G. (2020, August 28). Elite controllers may self-vaccinate against active HIV infection, gene study suggests. Aidsmap. https://www.aidsmap.com/news/aug-2020/elite-controllers-may-self-vaccinate-against-active-hiv-infection-gene-study-suggests

European Molecular Biology Laboratory. (2016, July 15). How new HIV drugs lock virus in immaturity: Study provides insights into workings of new HIV drugs and how virus becomes resistant. ScienceDaily. www.sciencedaily.com/releases/2016/07/160715112935.htm

HIV.gov. (2020, June 5). What Are HIV and AIDS? https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids

Paoli, J. (2013, October 6). HIV Resistant Mutation. Scitable. https://www.nature.com/scitable/blog/viruses101/hiv_resistant_mutation/

Saey, T. H. (2020, August 26). In a first, a person’s immune system fought HIV — and won. ScienceNews. https://www.sciencenews.org/article/hiv-immune-system-elite-controllers

Scripps Research Institute. (2017, April 10). New approach makes cells resistant to HIV. ScienceDaily. www.sciencedaily.com/releases/2017/04/170410154718.htm

Singh, M. (2013, September 21). In Life, Man Immune To HIV Helped Scientists Fight Virus. NPR. https://www.npr.org/sections/health-shots/2013/09/21/224506556/in-life-man-immune-to-hiv-helped-scientists-fight-virus

University Of Liverpool. (2005, April 3). Biologists Discover Why 10 Percent Of Europeans Are Safe From HIV Infection. ScienceDaily. www.sciencedaily.com/releases/2005/03/050325234239.htm

World Health Organization. (n.d.a). Estimated number of people (all ages) living with HIV. https://www.who.int/data/gho/data/indicators/indicator-details/GHO/estimated-number-of-people-(all-ages)-living-with-hiv

World Health Organization. (n.d.b). HIV/AIDS. https://www.who.int/health-topics/hiv-aids#tab=tab_3

World Health Organization. (n.d.c). Number of deaths due to HIV/AIDS. https://www.who.int/data/gho/data/indicators/indicator-details/GHO/number-of-deaths-due-to-hiv-aids

World Health Organization. (n.d.d). Number of new HIV infections. https://www.who.int/data/gho/data/indicators/indicator-details/GHO/number-of-new-hiv-infections