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Divergent subtypes
Jul 24, 2004

Dr. McGovern,

Welcome to this forum!

I have a Q: if you strongly suspected HIV infection despite repeatedly negative ELISA and Roche 1.5 tests after the 6 month window period (e.g. known HIV exposure in Europe, where many non B subtypes exist, CD4's plunging from 900 to <400, CD4/CD8 ratio inverting and chronic lymphadenopathy, pharyngitis, thrush and occasional shortness of breath and burning skin)...what diagnostic tests would you use to cover the spectrum of clades? My liver enzymes (ALT and LDH) are also elevated, though Hep B and C were excluded through antibody and PCR testing.

Contrary to frequent perceptions, I understand that the FDA does not require the HIV ELISA's to prove efficacy with all subtypes, just the main ones (essentially A through E, with usually a handful of specimens for non B's)...and Roche only claims that the Monitor 1.5 detects M group subtypes A through G (same with Bayer and it's bDNA). In Europe, there are subtypes such as J (for example, in Spain) and recombinants that include H and K subtypes.

I would appreciate your advice on what tests to do to embrace all the M subtypes. The US is mainly focused on B infection and the further the clade departs from B, the less sensitive the ELISA's (per a well respected HIV scientist and clinician who works in Africa) and certainly the plasma RNA tests. I also understand that the commercial DNA PCR test is not very good at detecting non B's.

What further tests would you do if I were your patient and you still suspected HIV infection, perhaps with a divergent subtypes?

Many thanks.

Response from Dr. Sherer

You describe a difficult and complex clinical situation that does not lend itself well to a single question and answer session on the internet. I will answer your question as best I can, but I urge you to seek the answer to this question with your physician and consultants with expertise in the diagnosis and management of non-B clades of HIV infection.

As HIV has spread through the world, the existing viral clades are mixing, leading to circulating recombinant forms (CRFs). Some of these may evade detection by the usual methods. This is particularly true of the antibody tests, as these may induce the production of unique antibodies for which there are no diagnostic tests.

Generally, direct detection of such forms via PC-RNA testing is more successful, though I note that the first option, the Roche 1.5 RT-PCR test, was negative after 6 months from exposure.

I would first suggest a repeat of this test. I would also advise again that you do this with an experienced physician, as your clinical syndrome is certainly suggestive, though not conclusively, of HIV infection.

Thereafter, there are other options, such as viral culture in PBMCs, and alternative measures of HIV RNA and DNA.



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