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HIV and Enteropathy
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Tropism Testing

What is HIV tropism?

What is tropism testing?

What tests are available?



 

What is HIV tropism?
HIV-1 enters target immune cells by interacting with the CD4+ T-cell receptor and 2 types of coreceptors: CCR5 and CXCR4. The tropism of HIV is defined by which coreceptor is used.1

HIV-1 infection of CD4+ T-cells begins with the fusion of the viral membrane and the target cell membrane. This is mediated by the binding of the viral envelope glycoprotein (gp120) to the CD4+ T-cell receptor on the target cell surface.1 A conformational change brought on by this binding exposes a binding site in the gp120 component of the Env for the CCR5 or CXCR4 coreceptors.2 Interaction with the CCR5 or CXCR4 coreceptor then triggers the fusion and entry of HIV-1 via gp41.3

The coreceptor used for HIV infection determines the tropism of the virus; CCR5-tropic HIV uses the CCR5 coreceptor, CXCR4-tropic HIV uses the CXCR4 receptor, and dual/mixed (D/M)-tropic HIV uses either or both coreceptors.4



What is tropism testing?
Tropism testing is a diagnostic tool used to identify which coreceptor HIV uses to infect target immune cells. The tests can be phenotypic or genotypic and are used to determine the coreceptor tropism of the dominant HIV population in patients.5 Tropism testing helps to provide information to enhance understanding of available treatment options.6



What tests are available?
Monogram BIOSCIENCES/LabCorp Specialty Testing Group offers a phenotypic assay called Trofile®.6 The plasma viral load of a patient must be ≥1000 copies/mL for this test. This assay involves the amplification of HIV RNA from a blood sample of the infected patient to make HIV particles that are specific to that patient. These particles are used to infect CCR5- and CXCR4-expressing cell lines. Once the cells have been infected and the particles have undergone replication, a signal detected from the expression of a reporter gene will identify the patient’s viral tropism.6

Monogram BIOSCIENCES/LabCorp Specialty Testing Group also has a test for patients who have an undetectable viral load on their current therapy, but require a regimen change for reasons other than virologic failure. Trofile® DNA, a phenotypic test that examines viral DNA in white blood cells infected with HIV, is effective even when plasma viral loads are undetectable.5,7,8 HIV envelopes encoded by the viral DNA are tested in a cell-based viral infectivity assay to determine which coreceptor the HIV population is capable of using.8

Genotypic assays are also available, such as the Quest Diagnostics HIV coreceptor tropism with reflex to ultradeep sequencing test, which is carried out on plasma HIV RNA. This test begins with standard sequencing of the third variable (V3) loop of the HIV-1 envelope gene, the primary determinant of viral tropism. If standard sequencing detects only CCR5-tropic virus, a more sensitive ultradeep sequencing test is performed to confirm that low levels of CXCR4-tropic virus are not present in the sample.9



References:
1.
Berger EA, Murphy PM, Faber JM. Chemokine receptors as HIV-1 coreceptors: roles
in viral entry, tropism, and disease. Annu Rev Immunol. 1999;17:657-700.
2. Monogram BIOSCIENCES, Inc. Tropism and HIV: viral entry. Trofile® Co-receptor
Tropism Assay Web site. www.trofileassay.com/Viral_Entry.html. Accessed May 21,
2012.
3. Clapham PR, McKnight Á. HIV-1 receptors and cell tropism. British Med Bull.
2001;58:43-59.
4. Monogram BIOSCIENCES, Inc. Tropism and HIV. Trofile® Co-receptor Tropism Assay
Web site. www.trofileassay.com/tropism_and_hiv.html. Accessed May 21, 2012.
5. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use
of antiretroviral agents in HIV-1-infected adults and adolescents. Department of
Health and Human Services. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Updated March 27, 2012. Accessed May 21, 2012.
6. Monogram BIOSCIENCES, Inc. FAQs - physician questions. Trofile® Co-receptor
Tropism Assay Web site. www.trofileassay.com/FAQs_Physician _Questions.html.
Accessed May 21, 2012.
7. Monogram BIOSCIENCES, Inc. Trofile® DNA. Trofile® Co-receptor Tropism Assay Web
site. http://www.trofileassay.com/. Accessed June 20, 2012.
8. Mayo Medical Laboratories. Test catalog.
http://www.mayomedicallaboratories.com/test-catalog/print/57159. Accessed June
20, 2012.
9. Quest Diagnostics. Test summary.
http://www.questdiagnostics.com/testcenter/testguide.action?fn=InfectDis/HIV/TS
_HIV-1_Coreceptor_Tropism.htm. Accessed June 20, 2012.




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