Claudia Singh Gill discusses the mechanism of HIV infection and the potential advances to treat the deadly retrovirus.
37.7 million people are living with HIV in 2020. Almost one million people die each year from the acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV). The HIV virus targets the cells in the immune system, preventing them from fighting infections. One of the most fatal diseases, HIV, remains a mystery to the entire scientific community. Recent evidence suggests stem cells as a potential therapy for targeting the infection. With the use of stem cell transplantation, patients can be cured of HIV but what’s more miraculous is when a patient’s immune system can naturally detect the virus and prevent it from spreading. Could this bring hope to those living affected? Such findings are yet to be discussed and up for debate.
HIV is a virus that targets the immune system. Over time, the immune system begins to fail and this increases the risk of infections. The retrovirus targets CD4+ cells which are cells that have a specific molecule on the membrane called CD4 (shown in the diagram below). The CD4 molecule helps immune cells communicate with each other which is very important when the immune system attacks foreign pathogens. The HIV virus attaches to CD4 by binding to gp120, a “finger-print” like molecule (glycoprotein) on the viral envelope coating the virus. The glycoprotein gp120 binds to a co-receptor at the host cell membrane. There are two main co-receptors at the cell surface which are CXCR4 and CCR5. These are present in T-cells, macrophages, monocytes, and dendritic cells which are vital for an innate immune response. Finally, HIV injects its single-stranded ribonucleic acid (ssRNA) into the host’s cell genetic material. During infection, the cell begins to replicate HIV viruses which exit the host cell and infect more cells. This virus induces viral tropism, a process that creates numerous mutations which initiate different strains of viruses inside the body.
First drug to treat HIV
Attempts for HIV cure began in 1964, when scientists developed azidothymidine (AZT), a potential drug for cancer treatment. After multiple trials, AZT proved to be ineffective but was identified as a potential cure to treat HIV/AIDS. In the laboratory, AZT repressed the replication of HIV without damaging normal cells. Further studies experimented with AZT in HIV patients and evaluated that the drug decreased further infections in the body, however, it instigated serious side effects. In 1987, the AIDS Clinical Trial Group (ACTG) began working on the use of AZT to treat HIV. It was concluded that prescribing lower doses could prevent the adverse effects. ACTG showed that AZT could be used to stagnate the mechanism of HIV but not cure it. Thus, AZT was the first demonstration to manage HIV infection.
Stem cell therapy and HIV
Stem cells serve as a prospective solution to multiple diseases, especially HIV. Current findings suggest stem cell therapy as a way to combat the virus. A stem cell transplantation on a patient in London with cells not expressing the CCR5 co-receptor was carried out. Viral load was a measure to detect the amount of virus inside the body. The findings showed undetectable viral load from HIV-1 in plasma up to 30 months after the transplantation. Similarly, the viral load in semen specimens was undetectable for about 21 months. Models on altering T-cells are a potential advancement against HIV as well. A model developed from the UCLA Center of Regenerative Medicine and Stem Cell Research engineered a modified virus that carried a special gene called the chimeric antigen receptor (CAR) gene. CAR is artificially constructed and inserted into blood-forming stem cells where they differentiate into modified CAR T-cells. These cell types are then able to locate and kill the infected HIV cells in mice models. Thus this evidence suggests stem cells as a promising possibility for treating HIV in humans.
“Esperanza patient” naturally cured of HIV?
Can a human be naturally cured of HIV? In recent news, a woman from Argentina became the second patient worldwide to be naturally cured of the virus. The 30-year-old patient under the name ‘’Esperanza’’ was diagnosed with HIV in 2013 and gave birth to a HIV-negative offspring in March 2020. Researchers have used several tests and scans on her cells but were unable to detect viable HIV. People like the Esperanza woman are the so-called elite-controllers of HIV which can suppress viral replication to low levels without the use of antiretrovirals. After such a phenomenon, scientists are searching for strategies to cure HIV with gene therapy by trapping the virus in cells, and enhancing the body’s immune system with therapeutic vaccines. Could such cases be the hope for 38 million people globally living with HIV? These findings are yet to be discussed and up for debate.
Want to find out more about the Esperanza patient? Read our new article here!
Written by Claudia Singh Gill and edited by Diana Jorge.
Claudia Singh Gill is a 2nd year neuroscience student, hoping to pursue a medical profession in the future. Find her on Instagram @clashunya or LinkedIn @Claudia Singh.