Human immunodeficiency virus (HIV) is said to have originated Hin chimpanzees from parts of West Africa in the 1930s. However, the world only came to know of the virus in the 1980s when doctors began to report rare types of illnesses. In 1987 the U.S Food & Drug Administration (US-FDA) approved the first antiretroviral drug, zidovudine. Over the years several drugs have been discovered which are used in combination with other anti-HIV drugs to treat HIV through antiretroviral therapy (ART).
ANTI-RETROVIRAL THERAPY (ART)
To understand how ART works it is important to understand HIV. When the virus infects a particular cell, it takes full control of that cell and uses it to make more copies of itself. Antiretroviral drugs such as zidovudine are used in combination with other anti-HIV drugs, usually from different classes to stop the virus replicating in the body.
There are 6 drug classes: Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs), Protease Inhibitors (PIs), Fusion Inhibitors (FIs), CCR5 antagonists and Integrase Inhibitors. All these classes have a different mechanism of action to inhibit replication, making it more effective in treatment. Although the antiretroviral therapy reduces the effect of HIV, it is not a cure. There are several barriers to universal uptake of ART such as having a medical regime everyday. These pills can also have long-term side effects and pose the possibility of developing a drug-resistant virus. It is also possible for viral rebound to occur within weeks of discontinuing ART which makes the patient in need for lifelong adherence.
BROADLY NEUTRALISING ANTIBODIES IN CLINICAL DEVELOPMENT
In a search for ART-free strategies multiple broadly neutralising antibodies (bNAbs) that target vulnerable sites on the HIV envelope are being assessed. Clinical trials have shown that viral rebound can be delayed significantly by bNAbs even after taking the patients off ART. This is more likely if the patients had started ART in early stages of their infection.
Previously single bNAbs showed little success in suppressing the virus as bNAb-resistant virus either already existed in the patient or was developed. To avoid this setback, researchers in the National Institute of Allergy and Infectious Diseases (NIAID) developed a combination bNAbs which targeted different parts of the virus envelope. This was successful in suppressing the virus for a longer period without ART. But the researchers faced a major challenge as bNAbs proved to be ineffective in suppressing HIV if the patients had a HIV strain which was resistant to one or both of the antibodies.
Thomas Splettstoesser (www.scistyle.com),CC BY - SA 4.0, via Wikimedia Commons
NEXT GENERATION BNABS
Going forward infrequent administration of antibodies along with long lasting ART antibodies is definitely possible on finding more potent and durable drugs and antibodies. These strategies will need to be further assessed in phase II and III of the clinical trials. The ultimate goal would be to identify antibody combinations which can also cover circulating variants so that screening for existing resistance to antibodies in HIV can be eliminated.
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