What Are Genetic Resistance and Tropism Tests?

Understanding the Tests Used to Tailor Your Antiretroviral Drug Therapy

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Selecting the appropriate combination HIV therapy is about more than just picking and choosing options from a treatment menu. Tests are routinely performed to determine the drug combination that will be most effectively suppress the viral population within a person's body, essentially tailoring the treatment to that individual. The tests include the HIV genetic resistance test and HIV co-receptor tropism assays.

What Is an HIV Genetic Resistance Test?

When infected with HIV, the viral population within a person's body is comprised a multitude of different mutations—most of which are harmless and unable to reproduce. A few, however, may be resistant to certain drugs used in HIV therapy. Putting a person on these drugs would allow the resistant viruses to multiply and proliferate, unchecked, until the drugs no longer have any effect.

In order to avoid this, tests are given to determine the type of resistant mutation that exist within a viral population. These are called genetic resistance tests. An analysis of these figures allows doctors to select the antiretroviral drugs that will work in combination to ensure complete viral suppression.

The two tests regularly used in the detection of genetic resistance are the genotypic test genotyping) and the phenotypic test (phenotyping). Each work differently in determining levels of resistance, often in compliment to each other:

  • The genotypic test works by amplifying and examining the genetic makeup (genotype) of the predominant populations of virus within a blood sample. In doing so, labs are able to determine which genetic mutations will likely confer to drug resistance.
  • By contrast, a phenotypic test measures how HIV reacts in the presence of antiretrovirals. After splicing genes from a patient's virus onto a standardized laboratory strain, technicians place the test samples into escalating concentrations of different antiretroviral drugs. An interpretation is made based on lab results and a review of previous antiretroviral use.

    Genotyping is recommended before the start of antiretroviral therapy. It can determine whether a drug-resistant virus has been transmitted and can also be predictive of a developing drug resistance. A genotyping generally takes around one to two weeks to complete.

    If treatment failure has occurred or there is an indication of a transmitted multi-drug resistance, a phenotypic test may be used in conjunction with a genotyping. These tests take around two to three weeks to complete.

    Resistance testing is best performed while a patient is taking a failing drug regimen, or within four weeks of stopping. The person's HIV viral load should ideally be above 1,000 copies/mL in order to ensure reliable results.

    What Is an HIV Tropism Test?

    CCR5 receptor antagonists are a class of drug that differs from other types of antiretrovirals. Instead on inhibiting a process in the HIV life cycle, these drugs bind onto a receptor molecule on the surface of the host CD4 cell. Blocking the receptor prevents HIV from entering and infecting the cell.

     CCR5 and CXCR4 are two co-receptors that HIV can use to enter a cell (the primary receptor being CD4 itself). 

    In order to identify these, a test called a HIV tropism co-receptor assay (also known as a trofile assay) is used to confirm the presence of CCR5 and/or CXCR4.  If a person's virus is shown to CCR5 tropic—meaning that uses CCR5 for entry—then that individual is deemed a candidate for a CCR5 receptor antagonist drug like Selzentry (maraviroc).

    Generally speaking, the vast majority of patients harbor a CCR5-utilizing virus during the early/acute stages of HIV infection. By contrast, patients with extensive drug resistance tend to harbor CXCR4 or dual-tropic virus.

    An HIV tropism test takes about two weeks to perform and requires a HIV viral load of over 1,000 copies/mL.

    Sources:

    U.S. Department of Health and Human Services (DHHS). "Guidelines for Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents." AIDSinfo Update. Rockland, MD; February 12, 2013: C9-C21.

    Connor, R.; Sheridan, K.; Ceradini, D.; et al. "Change in coreceptor use correlates with disease progression in HIV-1-infected individuals." Journal of Experimental Medicine. February 7, 1997;185(4):621-628.

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