HIV-1 messenger RNA in peripheral blood mononuclear cells as an early marker of risk for progression to AIDS
CommentOne of the most interesting aspects of this study, as the authors point out, is the ability of peripheral mononuclear cell HIV mRNA to predict a subgroup of patients who are long-term non-progressors. Determining the importance of host-factors and viral factors in this non-progression will be important. Plasma HIV RNA load after seroconversion was recently found to correlate with clinical outcome, and plasma HIV RNA is easier to measure, but plasma HIV RNA does not appear as predictive when measured later in the course of the disease. The exact clinical role of peripheral mononuclear cell HIV mRNA determination remains to be seen but appears promising.
November 27, 1995
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Reader CommentsSubject: HIV mRNA and progression to AIDS
Date: Wed, 29 Nov 1995 21:44:17 -0500
Although markers for disease progression are great for research purposes, I feel they are used much too often in clinical practice. The value in checking CD4 counts has not been in knowing how much time one had left, but in knowing when to start various interventions. Similarly, with the mRNA assays, we should be doing studies to find out if various interventions (drugs, etc.) used to decrease viral load have a measureable impact on clinical parameters such as survival and AIDS-free survival. The early identification of those with low viral loads may be of use to researchers trying to figure out how their immune system accomplishes this.
Roger Spitzer MD
I agree with Dr. Spitzer...I have measured HIV-RNA "viral loads" in several patients (often at their request) but do not know really what to do with that info. In a couple of patients who were clinically doing well but had low CD-4 counts, I was somewhat reassured that the RNA titer was not all that high, either...however, whereas I have a lot of experience with CD-4 counts, I really don't have a feel yet for the HIV-RNA...what is really high, what is worrisome, what is reassuring that things are OK for the present. I have been sending more of these to try to get a feel of what they mean clinically...I will certainly be interested in more articles about "viral load" measurements.
Received 11/29/95 (the way the form was set up, I didn't get a return address) --mj
I find viral load testing very helpful. The patient who is reluctant to take a drug can be convinced if the load is high, or for the patient with a the stable CD4 count with low viral load, you intervene when the load increases, which tends to predate the drop in CD4 count. The major obstacle is cost and reimbursement. Hopefully the recent reports from the Washington retrovirus Conference will improve that problem.
Ronald Hirsch, MD, FACP
Date: Sun, 03 Mar 1996
Don't we remember all the efforts on various cholesterol-lowering agents, many of which have actually increased mortality (eg. d-thyroxine, clofibrate)? The paradigm of (X is associated with death, so lower X) fails for many human diseases. Why can't we put aside these surrogate endpoints, especially for clinical, day-to-day use? The researchers may get some insights from this kind of study, but the human payoff is in the years-of-life saved in a real clinical trial, not in some petri dish or EMIT assay.
The problem with HIV is that new therapies and combination therapies are appearing and are being used all the time, and it can take years to detect effects on mortality. Some sort of surrogate validation is needed to try to weed out the ineffective treatments, even if these markers are imperfect. Your point is well-taken, however, and we need to keep reminding ourselves that surrogate markers are not what count, in final analysis. -- mj
August 28, 1997
It has been almost two years since this study was published. In doing a quick literature search, it would appear that measuring HIV mRNA in peripheral blood mononuclear cells has not become a common test. In fact, I couldn't find any recent articles on this topic.
On the other hand, the use of plasma viral load measurements for gauging disease prognosis and response to therapy has become quite accepted. Presumably, these measurements (plasma viral load by PCR) are simpler and cheaper than the technique discussed in this article while yielding similar information. -- mj
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