The Basics of HIV Drug Resistance

Errors in Replication Can Create "Mutant" Viruses Resist to HIV Treatment

HIV-1 infected CD4+ T-cell. Photo © National Institute of Allergies and Infectious Diseases (NIAID)

HIV drug resistance is simply defined as mutations to the genetic structure of HIV, which can makes certain viruses partially or fully resistance to antiretroviral medications. As these populations of mutant viruses continue grow, they eventually become the predominate virus within the "viral pool." When this happens, the person's HIV drug will become less and less effective until the treatment finally fails.

Newer antiretroviral drugs tend to develop resistance less slowly, although poor drug adherence can increase the risk of resistance by allowing the virus (include mutant viruses) to replicate unimpeded.

Why Does HIV Resistance Occur?

As cells reproduce, they make exact copies of themselves, growing in number with each replication cycle. But HIV is prone to genetic coding mistakes, in which the copies end up either misshapen or damaged. More often that not, these weaker "mutant" copies quickly die off.

In some rare cases, however, just the opposite happens. Rather than dying, some viruses are able to thrive because their mutated conformation does not allow the HIV drugs to either attach, penetrate or bind to them. So while the drugs are able to kill off the original predominate strain (known as the "wild type" virus), the mutated "variants" slowly take over to become the dominant strain.

Genetic resistance can also be passed from person to person through sex, shared needle use, or direct blood-to-blood exposure. If treatment failure occurs as result of HIV drug resistance, other classes of drugs be recruited to suppress the many variants within the person's viral pool.

See how HIV drug resistance develops in an informative, ten-part slide show. 

How to Detect and Confirm HIV Drug Resistance

There are simple blood tests that can detect HIV resistance and help doctors identify which medications will work best against the mutated virus.

Two types of resistance testing called genotypic and phenotypic assay are able to identify, respectively, which genetic mutations have occurred and how much these mutations confer to resistance.

  • Genotypic assays examine the genetic coding of the virus, first by
    • amplifying the genetic material and then looking to see what changes there may be compared to the control virus. Pathologist can then estimate what levels of resistance there are based on one or several genetic code variations. Some "single point" variations confer to high levels of resistance, while others are considered minor and only contribute to resistance.
  • Phenotypic testing differs from genotypic testing in that it takes the virus and physically exposes it to different concentrations of HIV medications. By doing so, it provides pathologists "real-world," measurable evidence of drug resistance.

These tests are commonly used to determine the best course of treatment in first-line and subsequent therapies in the U.S. and other resource-rich countries. However, the cost of genotyping and phenotyping is considered prohibitive in most resource-poor regions, with usage limited mostly to private sector patients.

Currently most insurance companies in the U.S., both private and public, pay for genotypic testing. Phenotype testing may not be covered by some insurers. Always check with your insurance provider to confirm whether these tests are included in your benefits package.

Learn more about how HIV genotyping and phenotyping work.

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