Virological markers

Although HIV mutates constantly, not every change causes resistance. If HIV is able to multiply when a patient is taking antiretroviral medications, the virus is said to be ‘resistant’ to the medication. Wild-type virus is the most common form of HIV. Once HIV mutates, it is no longer considered wild-type.

In a viral survival of the fittest, HIV that is resistant to a particular drug will multiply and eventually become the predominant form of virus in the body. If the person stops taking a particular ARV regimen, the virus no longer reacts against the missing medication, and there is an absence of ‘selective pressure’ driving the production of virus resistant to that particular drug.

The most recent treatment guidelines issued by the British HIV Association (BHIVA), the EuroGuidelines HIV Resistance Group, and the US Department of Health and Human Services all recommend routine use of resistance testing to assist in selecting an effective treatment regimen.

Unfortunately, availability and affordability limit access to many who would benefit from resistance testing. Hopefully, the increasing availability of low-cost diagnostic tests will mean that increasing numbers of antiretroviral-treated patients in poorer countries can have the level of viral load monitoring patients in industrialised countries often take for granted.

There are two types of resistance tests.

• A genotypic resistance test looks at the genetic code of an individual's virus to see if there are mutations present known to cause drug resistance.
• A phenotypic resistance test will show how much of a particular ARV drug is needed to control HIV.

Further information on the use of these tests can be found in the section on Drug resistance, in the subsection Resistance testing.

A tropism assay indicates viral preference for using the CCR5 or CXCR4 co-receptor after attaching to the CD4 receptor. Tropism testing should be used when considering the use of a CCR5 inhibitor drug in an antiretroviral regimen. It may also be of use in patients who are failing therapy on a CCR5 inhibitor-containing regimen.

Tropism test results indicate whether an individual's virus is R5 (or CCR5) tropic, X4 (or CRCX4) tropic, dual tropic, or mixed tropic (D/M). The Trofile assay has 100% sensitivity for detecting CXCR4-tropic virus.¹ An enhanced Trofile assay has been developed and is able to better identify dual/mixed-tropic HIV.²

A genotypic test, Geno2pheno, that looks at the V3 loop of the HIV's envelope protein has been developed that matches the Trofile assay's ability to detect CXCR4-tropic assay. This assay can be done during a standard genotyping test for drug resistance at no additional cost. This is a great advantage over the Trofile assay that can cost around USD $2000, takes three weeks for results, and can only be used effectively if viral load is above 1000 copies/ml.³

The section on Receptors, co-receptors and immunity to HIV provides further information on viral tropism.

This viral protein is found in the core of virions of HIV beneath the viral envelope. At certain times, it is detectable in blood, as p24 is made in quantities above that needed to make new HIV virions. Although p24 antigen is a crude measure of HIV replication, it is useful in predicting the risk of developing HIV disease in the future in individuals who have not yet made HIV antibodies.