The Lingering Threat of HIV
In 1981, young adults began getting rare lung infections. As the years progressed, more people fell ill, and scientists and doctors tried to figure out what was the cause. In the early 1980s, several labs around the world found HIV to be responsible for this. However, the first antiretroviral drugs were approved by the FDA in 1987, three to four years after the virus was identified (Avert 2018). Human Immunodeficiency Virus, HIV, was responsible for the epidemic in the 1980s, and is still a problem today. HIV can progress to Acquired Immune Deficiency Syndrome, AIDS, which makes people susceptible to other infections.
The immune system is responsible for protecting the body against pathogens that cause disease. While it does not function perfectly, it does provide a substantial amount of protection against the outside world. This system is exactly what HIV attacks. There are two arms of defense to the immune system: innate and adaptive. The innate immune system encounters the pathogen and relays the information to the adaptive immune system, which works to destroy or inactivate the threat. A key part of the adaptive immune system is a T-helper cell, also known as a CD4 cell. The CD4 cell helps to communicate between different types of cells, including B cells which produce antibodies that can neutralize the virus. HIV not only infects the CD4 cell, but inserts itself into the nucleus. Cells are constantly making proteins from the genetic information in the nucleus, and viral proteins from HIV are now included as well (AVERT 2018). The CD4 cells start dying, wiping out a key part of the immune system and leading to immune deficiency.
HIV is still being researched and studied in labs today. And while great progress has been made on the treatment, there is no vaccine for HIV; however, there are preventative medications one can take if they are exposed or at high risk. Pre-Exposure Prophylaxis (PrEP) has been shown to be highly effective at preventing HIV infection (CDC 2019). As of April 2020, only two people have been completely cured of HIV. In 2018, 1.7 million people worldwide became newly infected (MHAF 2020). While vaccines take years to develop, they can still be developed relatively quickly in times of need. Though there is no general cure for HIV, it has been found that antiretroviral medication can reduce the amount of HIV in the blood to an undetectable level, which helps prevent HIV transmission (CDC 2019). However, the medication must be taken for the rest of a person’s life and any interruption could result in a re-emergence of the virus. HIV can remain dormant for a long time in the nucleus, which makes it difficult to completely eliminate all viral genetic material (Sankaranantham 2019). Since HIV can always re-activate, it proves to be a particularly difficult pathogen to eliminate.
Vaccines utilize the body’s natural immune response to protect against future infection. Since the immune system retains memory cells, an introduction of a weak or inactivated virus should help prepare the immune cells for a potential infection. Unfortunately, a big part of the seriousness of HIV is that it can hide from the immune system. Even inactivated HIV, which is not hiding in the nucleus of cells, does not stimulate good immune response. There are many additional challenges, as HIV mutates quickly and most vaccines are targeted towards respiratory or gastro-intenstinal (GI) viruses (Case-Lo 2019). It is more common for a virus to enter the body through the airway or GI tract, as they provide a quicker means of the virus being transmitted from person to person. HIV is a sexually transmitted infection (STI), and can also be spread with the introduction of infected blood into the bloodstream. This adds to the differences between HIV and the common viruses that humans usually come into contact with.
Despite the numerous challenges, two people were completely cured of HIV. HIV enters the CD4 cell through a co-receptor CCR5. A very small percentage of the population (around 1%) contains a mutation that leads to having no CCR5 on the cell surface. The mutation is called Delta 32, and has been shown to lead to immunity to HIV (Sankaranantham 2019). In 2005, a man who was HIV positive learned that he had acute myeloid leukemia. Through the rounds of chemotherapy, he developed fungal pneumonia and a severe infection, but recovered in both instances. His doctor found more than 200 matches for a potential stem cell transplant and chose a donor with the CCR5 Delta 32 mutation. When the patient received the transplant, the antiretrovirals were stopped. Multiple blood tests were taken and it was determined that the patient no longer had any HIV in his blood and was proclaimed as cured in 2008 (Brown 2015). Doctors tried to cure many other patients with this method, however, they could not replicate the results. They found another form of HIV that utilizes a different receptor, and thus can infect the cell even with a CCR5 Delta 32 mutation (Kempner 2019). Then, another person was cured of HIV, with a very similar story to the first person. In 2003, he discovered he was HIV positive, and in 2011, he learned he had a Stage 4 lymphoma. There was added difficulty in simultaneously undergoing chemotherapy and taking HIV medications, and dosages often had to be recalculated as a result. With the treatments not working, the patient found a doctor who was an expert in bone-marrow transplants, including with HIV positive patients. A matched donor with the CCR5 Delta 32 mutation was identified, and he received a transplant in 2016. After his recovery from the transplant, he stopped his HIV medication and the doctors found no trace of a present HIV infection (Mandavilli 2020). Today, both men are doing well.
Two people being cured of HIV is great news. It provides hope and motivation for the scientific and medical community to add more people to that list. Unfortunately, a cure or vaccine is still a while away. Both patients had severe cancers and did not respond to chemotherapy, which resulted in a stem-cell transplant. These are risky and the survival rate for a person receiving a transplant is about 50% (Brown 2015). A person also needs to be matched with a donor that has the CCR5 Delta 32 mutation, which is not common in the general population. There was a controversial experiment done in 2018, where a Chinese scientist genetically altered embryos of twin girls to have the CCR5 Delta 32 mutation (Kempner 2019). This raised ethical concerns. Genetic alteration is not precise and could have impacted other genes. Also, the CCR5 Delta 32 mutation gets rid of an immune cell receptor, and so there might be some subsequent issues down the road. While there are still many challenges, there are many, many labs and resources around the world focused on preventing HIV infections and finding a more definitive cure. Already, there are more treatments based on this mutation. Maraviroc is a drug that binds to the receptor and prevents HIV from binding. There are also gene therapies being tested, to introduce immune cells to eliminate the receptor (Kempner 2019). The scientific community is getting closer to developing a cure.
Works Cited
Avert. (2018). Avert: Global information and education on HIV and AIDS. Web. Retrieved from https://www.avert.org/about-hiv-aids/what-hiv-aids
Brown, Timothy Ray. (2015). I Am the Berlin Patient: A Personal Reflection. AIDS Res. Hum. Retroviruses 31(1): 2-3. Doi: 10.1089/aid.2014.0224
Case-Lo, Christine, Reviewed by Cochrane, Zara Risoldi, PharmD. (2019). HIV Vaccine: How Close Are We? Healthline. Retrieved from https://www.healthline.com/health/hiv-aids/vaccine-how-close-are-we
CDC. (2019). HIV. CDC: Centers for Disease Control and Prevention. Web. Retrieved from https://www.cdc.gov/hiv/basics/whatishiv.html
HHS. (2020). HIV Vaccines. HIV.gov. Web. Retrieved from https://www.hiv.gov/hiv-basics/hiv-prevention/potential-future-options/hiv-vaccines
Kempner, Martha. (2019). The Genetic Mutation Behind the Only Apparent Cure for HIV. TheBodyPro: For the HIV/AIDS Workforce. Web. Retrieved from https://www.thebodypro.com/article/genetic-mutation-behind-hiv-cure
Mandavilli, Apoorva. (2020). The ‘London Patient,’ Cured of H.I.V., Reveals His Identity. New York Times. Retrieved from https://www.nytimes.com/2020/03/09/health/hiv-aids-london-patient-castillejo.html
Sankaranantham, Murugan (2019). HIV – Is a cure possible? Indian J. Sex. Transm. Dis. AIDS 40(1): 1-5. Doi: 10.4103/ijstd.IJSTD_112_15
