Test for the virus antigen viral DNA and RNA subtypes mutants

Viral antigens are present in serum, in particular the HIV core antigen, p24. This is only detectable for as long as it is in excess of antibody to p24, typically at the outset of infection. Tests for this HIV antigen are commercially available, and they assist in the diagnosis of early infection and the recognition of infection in infants. In practice, however, tests for HIV antigen have proved of limited value due to lack of sensitivity, although this may be enhanced by preliminary acid or alkali dissociation of immune complexes in the specimen. Viraemia may also be recognised by isolation of HIV from plasma in cultured lymphocytes, but this is time consuming and not especially sensitive. Essentially it has become a research tool.

HIV can also be detected in specimens in the for m of genome sequences. Though only rare lymphocytes carry the HIV genome, the polymerase chain reaction (PCR) can be used greatly to amplify chosen HIV genome sequences in those clinical specimens that contain these small numbers of infected lymphocytes. To a large extent, therefore, viral culture has been superseded by PCR amplification of HIV DNA extracted from mononuclear cells in the circulation. Even more commonly, reverse transcription and amplification of HIV RNA is now being used to detect and quantify virus present in blood. While these procedures are no more accurate than anti-HIV assays and much more expensive, they may be useful in diagnosis, for example in infancy when any anti-HIV detected may be of maternal origin. PCR amplification also provides rapid access to the HIV genome and can lead to characterisation of an HIV isolate to strain level. The (semi) quantification of viraemia (i.e. to within about 0.5 log10 ) is an important determinant of the need for, and the effect of treatment. It is especially useful as the choice of antiviral combinations widens. Targets for genome amplification include the genes coding for the main envelope, core and transcriptase proteins. On the basis, particularly, of analysis of the sequences of amplified sections of the envelope gene, HIV-1 has been subtyped — so far from A to K. In some cases the sequences found in the various HIV genes are not concordant, showing that recombination occurs in HIV.

Figure 2.5 The evolution of plasma laboratory markers of the naturalisation of HIV infection ('x' axis not to scale). The course of HIV may now be modified by combined antiviral treatment which will suppress HIV PCR reactivity but not usually modify the anti-HIV response

Sequencing of PCR "amplicons" is also the basis for proving HIV transmission events in special settings, for example, health care.

The growing use of antiretroviral drugs, especially singly, has encouraged the emergence of resistance. This is usually associated with point mutations in the HIV genome. As the common resistance mutations have become better known, testing for them has begun to be used to guide changes in therapy. There is also growing interest in the epidemiology of those mutations that confer resistance for the obvious reason that a highly transmissible resistant mutant might be untreatable and assume an epidemic character.

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