February 27, 2002
It has been noted for the past few years that whatever regimen brings viral suppression to below 50 copies leads to the most prolonged control. Patients whose viral load gets close to 50 copies, but never actually gets there, do have a higher risk of viral rebound on most, if not all, regimens.
However, it has also been commonly observed that many who have a viral load below 50 copies will, on occasion, have a reading above 50 copies. The term "blip" has been used commonly as a way to describe these transient rises -- this term generally refers to rises that are temporary, with the next viral load readings going back below 50 copies.
For the past few years, researchers have explored the consequences of such "blips" on future viral control. Last year, studies done with those on their first regimen clearly show that the rate of eventual viral rebound over the next year in those who have these "blips" is similar to those whose viral load readings are consistently less than 50 copies. This presentation by Dr. Havlir reviewed the outcome of patients whose viral loads are controlled to below 50 copies on their current regimen, but who have experienced virologic rebound on previous combinations. This group is considered to have a more difficult time getting viral suppression, and with the underlying viral resistance, it is reasonable to explore the consequences of "blips" for this group as well.
Two studies were used for this analysis -- one study (ACTG 398) was done for those with rebounds on prior protease inhibitor-based regimens who were now on an amprenavir-based regimen containing four or five total antiviral agents. The other was ACTG 359, for those who had rebound on an indinavir-containing regimen and were now on a dual protease inhibitor regimen based on saquinavir.
The results from both studies were similar, and support the observations from those suppressed on their first combination -- "blips" do not appear to predict an increased risk of rebound when compared to those who never have "blips." The rate of those with "blips" did differ in the two studies -- ranging from 11-33 percent. The average viral load of a "blip" was about 80 copies, although some were as high as 500 copies. Not surprisingly, the CD4 counts of those with "blips" were similar to those with sustained suppression. It was noted that those who stopped one of the active medications did have viral rebound -- but these increases in the viral load were distinct from "blips" as the cause was the removal of one or more active antivirals. The presentation by Di Mascio reviewed the findings of the Aaron Diamond group from several treatment studies, and showed very similar findings -- "blips" did not predict subsequent loss of viral control on a variety of regimens. They also noted that this was a fairly frequent event -- noting "blips" in about ten percent of all viral load measurements. They also noted no evidence of resistance in these patients whose viral load remained suppressed despite these transient viral load rises.
Clinically, these results continue to confirm observations made in the past few years -- a regimen that is potent enough to get to a viral load of less than 50 copies will, for as many as a third, be associated with temporary readings above 50 copies. If these occur despite continued medication adherence, and not because someone has stopped taking one or more of their meds, it is reasonable to continue with the same regimen and just recheck the viral load in the next month or so. These studies continue to note that "blips" are transient, and do not predict the loss of viral control, at least for the period of time of these studies. Caution is however warranted since there may be an important difference between a temporary rise above 50 that is again suppressed on the next measurement, versus someone who has persistent measurements above 50, with a viral load trend that is increasing. This latter pattern is clearly a different one, and one that may indeed suggest that a loss of viral control is occurring. Overall, these studies add a level of comfort since this fairly common pattern of "blips" is one we can expect, and requires only monitoring, rather than an alteration in regimen that may not be needed, as "blippers" stay as suppressed as those that just never blip.
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