May 21st, 2008

When Expert Clinicians Disagree

Periodically, in AIDS Clinical Care, we publish a case in the “Antiretroviral Rounds” section and ask two clinical experts in our field how they would manage such a patient. The most recent case elicited responses that were 180 degrees different.

(This is exactly what we’re after, by the way — why present a case in which everyone would do the same thing?)

The full details of the case are on the AIDS Clinical Care web site, but in brief: A 50-year-old man with longstanding HIV was admitted to the hospital with gallstone pancreatitis, during which time he experienced virologic rebound since he couldn’t take anything by mouth. Athough for years he’d been mostly virologically suppressed — with some values between 50 and 500 cop/mL — on a regimen of TDF/FTC and boosted fosamprenavir, the resistance genotype sent after viral rebound showed extensive triple-class drug resistance. Resuming therapy after his recovery led to a drop in the viral load again to undetectable. Should this patient change treatment?

One of our respondents (Joe Gathe) said — confidently — to stay the course, no change; the other (Rick Elion) said — assuredly — to change to a completely new regimen. Is it possible that both are right? After all, both these guys have extensive clinical experience in HIV care and research; are widely respected in the field; and were able to cite excellent reasons defending their management decisions. These are the kind of doctors you’d send a family member or friend to if he/she had HIV.

So I’ll go out on a limb and say yes, both were right — but for the non-clinician, the fact that there are such different ways to manage one problem can be unsettling. Indeed, our executive editor (a non-MD) said she felt “uncomfortable” with these vastly different approaches to treatment.

Needless to say, the case is drawn from real life, but before I divulge how it was managed, I’d be interested to hear what others would do.

4 Responses to “When Expert Clinicians Disagree”

  1. Good arguments on either side but I would come to the same conclusion that Joe arrived at. We should always treat the patient and not the lab value, especially if the lab report makes no sense. The current regimen should not be able to suppress a viable virus with this genotype. Either the virus is not viable or the report is wrong. Neither of these scenarios require a change of therapy.

  2. Dr.Nadaraja Bathirunathan says:

    This is an interesting case showing the effect of immunity especially innate immunity on chemotherapy. It is the patient’s defence mechanisms which make chemotherapy effective.
    The pancreatitis lowered the immunity , the chemotherapy ceased to be effective and indeed selected for the resistant organisms. After recovery from pancreatitis the patient returned to his oiginal status.
    There is absolutely no need to change the therapy . The new drugs may be more toxic, more expensive, and have undesirable side effects and are uncalled for. Also you are one ladder up on resistant drugs.
    There has been a tremendous progress in our understanding of innate immunity which plays a powerful role in keeping us healthy. All medical personell should be famliar with it. It is our body which cures itself. The physician can only help or hinder it.
    Just to give you an example the best method of generating resistant mycobacteria would be to treat a tuberculosis patient with AIDS. Malnourished, stressed,unhappy and unloved patients are difficult to treat.

  3. Elizabeth Jenny-Avital says:

    The paradigm that resistance causes virologic failure is based mostly on observations of genotypic resistance that coincides with virologic failure. Our inability to measure “below the radar” resistance in patients who are virologically suppressed prevents us from knowing exactly how much resistance exists even in patients who are doing well. If we use a two-inch net to catch fish, we erroneously conclude that all fish are bigger than two inches. Same with most of our understanding of resistance—since we look for it in patients who are failing, we only find it in patients who are failing and perhaps erroneously believe that it does not occur in patients who are succeeding. When we do not find resistance in patients who are failing, we blame it on poor adherence, or as in the case of the enhanced trophile story with the CCR5 inhibitors, we develop better tests to look for resistance in failures, but not in suppressors. The same is true for adherence—we look poor adherence in failures but do not as vigilantly count pills or check refill dates in those who are doing well.

    I have similar examples to that in the case described. One patient, for example, was on trizivir for years with intial VL> 100,000/ml. He maintained a good CD-4 count but only took the trizivir daily at best and as a result, he had accumulated many TAMs and M184V. Rather than salvage him, given his clinical stability and lack of commitment to HAART, I continued the trizivir. At some point, he decided to mend his ways, and suppressed while adherent to BID trizivir.

    Exactly how much poor adherence and resistance jeopardizes outcomes is not altogether clear. Let us not forget that prognostic interpretation of resistance tests is validated by virologic observations in patients over fairly short periods. The meaning of resistance in myriad of clinically nuanced situations is by no means well established.

    I applaud the clinician for doing the resistance test just to learn. Only more time on the same regimen will tell us whether that regimen is prematurely doomed.

  4. EK says:

    I would not change the meds at this point. His low viral load could be due to changes in his replicative capacity and we might get a period of sustained response. This gives time to see what new drugs come on the market and to learn about the newer more recently approved ones.

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

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