Antiretroviral therapy: a key to helping HIV patients

Human Immunodeficiency Virus, commonly called HIV, is a sexually transmitted disease that affects approximately 40 million people worldwide and is mostly common in ages 15-49 years. It is spread through direct contact with the blood, semen, pre-seminal fluid, and vaginal fluids of an infected person through mucous membranes—contact with male and female genital tracks. Additionally, HIV can be spread through breast milk from mother to child—studies have shown that infants likely contract the virus when the milk makes contact with the mucous membranes of the gut. 

How does HIV affect immune cells?

HIV is a retrovirus—enveloped RNA viruses that can evade the immune defense system and live within host cells indefinitely. To infect cells HIV uses several mechanisms to make contact with the host cell's membrane. This involves the binding of HIV envelope protein (Env) with the cell receptor CD4 of an immune cell (T-helper cells). Env then binds to a co-receptor on the surface of the cell membrane, triggering membrane fusion. Membrane fusion leads to formation of a fusion pore where HIV successfully enters into the cell's cytoplasm through. 

Following this, HIV converts its RNA to DNA using enzyme reverse transcriptase and then uses integrase enzymes to become a permanent part of the host cell’s DNA. This allows HIV to replicate at a rapid rate, eventually causing the cells to bloat and rupture, killing the cell all while also “hiding” from the immune defense system and going into latency. Such a process is what weakens the immune system as there is a significant depletion in T-helper cells—cells that fight off infections and diseases.

The evolution of ART

For the reasons above, HIV is almost impossible to cure. While research is still being conducted to find a cure for HIV, most studies are now being diverted to Antiretroviral Therapy (ART). ART is a revolutionary treatment introduced in the late 198 0s that aims to prevent transmission of HIV, prolong survival, improve immune function and increase CD4 cell count, and improve overall mortality. 

The first drug released in the late 1980’s was Zidovudine, a nucleoside reverse transcriptase inhibitor (NRTI) that essentially prevents HIV’s RNA from being converted to DNA. This restricted replication hence increasing T-helper cell count. However, while shown to improve the condition of HIV patients, zidovudine did not work well on its own and caused drug resistance from prolonged use. 

Combination therapy was later introduced where scientists discovered zidovudine to be effective when used alongside another NRTI (dideoxycytidine). This combination did improve CD4 cell count and the overall condition of most patients, not in patients with advanced HIV who had prior use of zidovudine alone. 

Now, several medications such as NRTI’s, non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, and integrase inhibitors have been introduced and are used in a combination of three (Triple-Drug Therapy) to help suppress viral load to undetectable levels in the blood and improve the overall quality of life for patients. Triple-drug therapy can be tailored by doctors to improve the patient's condition.

HIV is a sexually transmitted, chronic condition that affects less than 1% of the world's population. There is no cure for HIV, however, treatments (ART) have been introduced to reduce the viral load of HIV as well as improve the overall quality of life of patients. Compared to the past where these medications had to be taken multiple times a day, often causing severe side effects, patients can now take just a single tablet daily. This has changed the course of HIV treatment, allowing people to live lengthy, normal lives with the disease. 

Written by Sherine A Latheef 

Related article: CRISPR-Cas9 to potentially treat HIV

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