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Your answer to a question about falling CD4's despite undetectable VL
Apr 20, 2004

Dr.Lee, I read a post in which you advised someone whose CD4's were continuously dropping despite an undetectable VL, not to worry and to stay on the same drug regimen.

I have seen many questions on this website and another HIV forum from different folks in this situation and all the doctors say not to worry if VL is suppressed (though sometimes to get off AZT that can lower WBC's, part of the CD4 calculation formula).

My Q is this: underlying all this advice is the assumption that the RNA VL tests are accurately quantifying viral copies. Yet none of the doctors asks if the subtype is a non B,in which case a Roche 1.0 assay would not accurately quantify..would need a 1.5or bDNA.The other question is whether some of these cases may not involve people with a subtype or mutation that even a bDNA or 1.5 may not be able to quantify - These assays only claim to be able to quantify M subtypes A through G and I gather that there are some issues with the 1.5 being able to fully quantify one or two of these subtypes. In addition, what about subtypes H through K of Group M for which there is no assay or infection with HIV-2 which is the same thing.

I guess my question is: couldn't some of these people with undetectable VL's have a subtype, combination of subtypes (through initial infection or later super infection) or couldn't HIV have mutated within them after a while of drug treatment such that the VL tests are not able to detect or quantify their RNA VL?

I would appreciate your thoughts on this.The scary thing about HIV is how it genetically keeps evolving...just as new subtypes and groups were created, additional new ones are in the process of being created. How is it possible to fully keep track of this and how far behind genetic mutations in HIV do VL tests and even ELISA tests lag?

Another question is, if in fact VL is suppressed below say 50, could someone with say 20 or 30 viral copies have a virulent form of the virus such that the low number of remaining viral copies could be destroying CD4's at a faster rate than normal? (bearing in mind too that only asmallpercentage of HIV is in plasma RNA)? Could the RNA VL test, while a dramatic breakthrough, still be an imperfect gauge of whether HAART is really taming the viral levels?On this issue, I have read various posts by people who have undetectable VL's, but who say they are really ill with many viremic symptoms. Could CD4's and symptoms sometimes be realted to virulence of the virus, not just numbers...or would a virulent virus tend to result in large numbers in plasma RNA?

I would very much appreciate your thoughts on the above and whether it is possible that at least some of these various cases of falling CD4's despite apparently undetectable VL's could not be due to the fact that the VL's are in fact not suppressed, nor being accurately quantified due to strains or mutations involved. If so, how can an HIV clinician address that possibility...again, even Roche and Bayer (bDNA?) do not claim that their VL tests can detect beyond M group G or even mutated or recombinant versions of M group A through G.

Or am I just wrong and these assays are reliable in detecting all strains and mutations? (I read that bDNA has more probes than the Roche 1.5...does that mean it is morelikely to detect all subtypes?).

Many thanks.

Response from Dr. Lee

To respond to your first question, the following is my answer from a question in switch/simplify dated Jan 15 04 on "Low VL":

You mentioned that you are from a third world country, although you did not specify which one. As you may know there are different families (clades) of HIV which are predominent in different areas of the world. In the Northwest Hemisphere (US and Canada), Australia and Western Europe the Clade B virus is the most common type of HIV. Therefore in those parts of the world, the viral load tests mostly measure Clade B viruses and may miss or undercount viruses from other clades.

The practical application of this is that people who have non-B clades of HIV cannot rely on the viral load numbers which come from tests for Clade B viruses. The tests that are routinely used in the US for example undercount the non B clade viruses.

One of my patients who was infected in East Africa has always had a very low viral load (<1000)on the conventional tests. However, when we tested his blood for non B viruses, his viral load was actually more than 250,000.

If you were only infected for three years, as you explained, your viral load would likely have been greater than 509 to have affected your CD4 count to the 392 level.

In your situation, the viral load tests may not pick up the actual level of virus active in your system. If that is the case,treatment decisions may be more complicated. Ask your physician about the interpretation of your viral load in light of this clade issue.

Another issue related to the clade differences is the choice of combination therapy. The different clades may have different susceptibilities to the medicines, especially the protease enzyme inhibitors. Again, check with your doctor about the cross-clade activity of your medications.

As an addendum- some of the tests in the US claim to pick up all the clades now, but not all are the same. Your doctor should check with the lab.

Second question related to the virulence and possibility that a low level but very virulent virus could account for some folks who have a decreasing T4 despite ND VL- Doubtful, but theoretically possible. Certainly what is unknowable today will be common knowledge tommorrow. Generally the T4 damage is related to the infection with HIV virions. Therefore the more virions the more T4 damage.

Keep thinking. It is good to question and your questions are well-thought out. Be well.



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