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So which is it?
Jul 26, 2008

Looking back through the archives I noticed that on April 26, 2004 you stated that CRFs can be detected by standard Elisa tests, but on July 24, 2004 it is contradictory when you say that CRFs may elude diagnostic assays and that PCR tests are more reliable. So which is it? Can the more than 30 CRFs be "caught" by an Elisa test if the Elisa detects all of the subtypes (A-K) that are in the various CRFs. Thanks in advance for you time and answer.

Response from Dr. Sherer

I don't have the information from the specific fora and dates that you are referring to, but I'll do my best to answer your question.

There are at least two different tests and issues that you may be concerned with. The first is whether standard ELISA tests will give positive results for HIV antibodies following infection with a CRF or 'circulating recombinant form', i.e. a unique subtype formed by recombination of two or more viruses of the subtypes A-K. I believe that this is your central concern, i.e. proof of active HIV infection when infected with a CRF.

The standard method to confirm a past HIV infection is with two ELISA tests, followed by a confirmatory Western Blot, which is a direct test of the presence of the viral proteins in the blood.

The other test that you may be concerned with is a viral load assay, i.e. an HIV RNA polymerase chain reaction (or 'PCR' test), in the presence of an infection with a CRF. This test is useful to monitor the response to ART, to gauge the likelihood of an HIV opportunistic infection and/or HIV disease progression based on the viral load 'set point', to diagnose acute HIV infection (with a positive HIV RNA PCR test and a negative HIV antibody test), and to assess risk of sexual transmission.

To take the first test: An HIV antibody test is 99.5% sensitive for detecting HIV infection, and 99.99% specific. These overall numbers include infection with CRFs. It is quite possible that I used these numbers to reassure a questioner that, with a high (but not perfect) degree of certainty, that a standard HIV test, consisting of two standard ELISAs and a confirmatory Western Blot, would be sufficient to establish the presence of an HIV infection with a CRF and, if repeatedly negative, to establish the absence of an HIV infection with a high degree of certainty.

I may also have said, however, that no laboratory test is 100% perfect, and there are some circumstances under which a false negative HIV antibody test can occur. These include: 1) a test performed within the 1-4 week 'window' period during which infection has been established, but the ELISA test has yet to turn positive; 2) aggamaglobulinemia, in which the patient lacks the ability to produce globulins in response to infections; 3) a technical or clerical error, in which the test is improperly performed or reported; or (getting to your question) 4) infection with an N or O strain or HIV-2.

Note that this last example is not the same as being infected with a CRF. CRFs are recombinants of subtypes A-K, all of which are M (or 'main') subtypes. As I noted above, these infections are detected by current HIV antibody tests.

There are three major categories of sub-types, i.e. M, N, and O. N and O subtypes are rare. As of the year 2000, only two O subtypes were reported in the US, and no N subtypes.

Finally, HIV-2 infection causes a false-positive HIV antibody test in 20-30% of cases, and may require a specific test with activity against HIV-2, which some, but not all, current ELISA assays test for.

In sum, for detection of infection with an HIV CRF, a standard ELISA + Western Blot testing is sufficient. Rare forms of HIV infection with either N or O sub-types may cause a false-negative HIV ELISA test and require special testing, for which communication with the US CDC is necessary. The circumstances under which a request for such testing might be warranted are quite uncommon, e.g. a characteristic HIV clinical syndrome, a history of travel to areas of the world endemic to subtypes N or O, and repeatedly negative HIV antibody testing. And, as above, there are other possible reasons for false-negative HIV Ab tests to be aware of.

Regarding viral load assays, the current HIV RNA PCR tests are sufficient to detect viral loads in patients who are infected with CRFs, although there is greater test performance variance with some CRFs, specifically A-D, F, G, CRF01_AE, CRF01_AG, and group O). These tests are useful for diagnosing acute HIV infection, predicting the likelihood of transmission, predicting the rate of HIV disease progression, and for therapeutic monitoring.

I suggest that you talk to your doctor about your concerns and this response.

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