What Causes HIV Drug Resistance?

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  • Written By: Jillian O Keeffe
  • Edited By: PJP Schroeder
  • Last Modified Date: 09 November 2019
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The human immunodefiency virus (HIV), which causes Acquired Immunodeficiency Syndrome (AIDS), is a complex disease to control. Anti-HIV drugs target specific characteristics of the virus. As the virus mutates easily, these characteristics can change, and HIV drug resistance can occur. The high rate of mutation means that a person who has HIV does not carry only one strain of the virus. The myriad virus strains all have different characteristics, and all may have the potential to adapt to medication.

The virus is made of ribonucleic acid and is part of a group of viruses called retroviruses. It does not contain enough genetic information to reproduce by itself so it uses the machinery of the host cell. The viral genome produces essential protein products. The virus genes are prone to mutation, and these changes in sequence can produce altered protein products. These altered protein products are important in HIV drug resistance.

HIV drugs target specific sites on viral particles or on their genetic products. Major drug targets are the enzymes produced by the virus. For example, an essential part of HIV replication is the enzyme reverse transcriptase. This enzyme uses the host cell's machinery to reproduce itself. Another important enzyme target is protease, which cuts up long viral protein chains into useful products, like reverse transcriptase and structural molecules.


One effective drug targeting system binds to the active site of the enzyme and prevents it from carrying out replication. A genetic mutation in the viral genome can produce an altered version of this active site. The drug may then not be able to bind to the site and block the enzyme.

Another HIV drug resistance mechanism is to alter the structure of a drug to render it useless. For example, a drug may target the genome of the virus to prevent the genes from being expressed and essential viral proteins from being made. Mutations in the genome can make the binding site unrecognizable to the drug. A mutated genome can also produce enzymes that can alter the bound drug's structure, which can render it harmless to gene expression.

HIV treatment regimens generally use a combination of drugs to control the progression of HIV infection. Even three or more drugs cannot eradicate each of the many strains that are present in one infected person. The mutations that prevent the drug from acting may already be present in viral strains, and when susceptible strains are killed off, the resistant strains take over and multiply.

Two virus particles can also swap genetic material while replicating, which forms a new virus that may be resistant to drugs. HIV drug resistance can either develop in an infected person, which is known as acquired drug resistance, or can be transmitted from one person to another, which is known as transmitted drug resistance. Failure to follow a drug regimen correctly can encourage the development of drug resistance.


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