What is the role of drug resistance testing in the management of HIV infection?

Updated: Jun 23, 2020
  • Author: Philip A Chan, MD, MS; Chief Editor: John Bartlett, MD  more...
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Drug resistance testing

HIV rapidly develops resistance to antiretrovirals when they are used as single agents, but resistance can occur even with combination therapy. In addition, transmission of HIV from an individual who is already receiving therapy might result in drug-resistant virus being present even in treatment-naive individuals. For this reason, many experts recommend performing resistance testing before starting therapy. Nevertheless, the largest use of these tests is in the management of patients with established HIV disease.

There are two main methods to detect antiretroviral resistance in HIV: genotypic and phenotypic testing. Both are performed in specialty laboratories.

Genotypic testing relies on the fact that many drug-resistance mutations have been well described and characterized from in vitro studies or clinical cohorts of patients in whom HIV treatment is failing. [35] Amplification and sequencing of target areas of the genome can provide rapid detection of probable resistance mutations to several antiretroviral medications simultaneously.

The main limitations of genotypic testing are that sufficient virus must be present for testing. Resistance testing cannot be performed in the presence of a low viral load. Only those mutations known to confer drug resistance can be tested for. In addition, the presence of low-level resistance might be missed in a mixed population of viral pseudospecies, a situation that often exists in persons infected with HIV. In general, this subpopulation would be expected to expand in the face of pressure from treatment, and later testing should detect it.

Phenotypic testing is performed with actual viral culture, testing the virus’s ability to replicate in the presence of antiretroviral drugs. It too relies on sufficient virus being present to test and is limited in that it is more labor intensive. It may, however, be better at detecting mixed populations of resistant and sensitive pseudospecies.

Resistance testing is an important part of choosing an antiretroviral regimen and can be useful when monitoring treatment response. However, treatment should not be delayed while awaiting the results of resistance testing. Antiretroviral regimens can be initiated at diagnosis, and regimens can be modified as needed. [16, 36]

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