Predictive Value of Viral Load "Blips" in Patients with Viral Suppression
A couple of very interesting trials were conducted to determine the frequency and significance of intermittent episodes of increases in viral load (HIV RNA) between 50 and 200 or 500 copies. These studies looked at whether these episodes, or "blips," in viral load can be used to predict subsequent virologic rebound. The first study (ACTG 343) examined people treated with indinavir (Crixivan, IDV), zidovudine (Retrovir, AZT, ZDV) and lamivudine (Epivir, 3TC) who achieved viral loads below 50 copies by 24 weeks of therapy. "Intermittent viremia," or blips, were defined as a viral load of less than 50 copies, with a subsequent measure above 50 copies and a return to full suppression. Virologic failure was defined as two consecutive HIV RNA measures above 200 copies. Intermittent viremia occurred frequently. Forty percent of subjects with viral suppression after 24 weeks of therapy had experienced a blip. However, these episodes were not associated with a higher rate of viral rebound, compared to people who had no blips.
Another study evaluated people who had transient increases in viral load above 50, but below 400 copies, after the virus had been suppressed to fewer than 50 copies for at least four months. On follow-up, 75% (24 of 32) patients reestablished a viral load of less than 50 copies without any change in therapy. Eight patients failed to re-suppress viral load and progressed to have higher viral load levels. Of the four people in this study who were on their first HAART regimen, all achieved re-suppression. The authors concluded that a rise from an "undetectable" viral load to a measurement between 50 to 400 copies is not necessarily an indication of actual or impending virologic failure, and they suggested that the most appropriate response is to retest the person's viral load.
These two studies raise some very interesting questions about the implications of intermittent low levels of viral replication, or blips, and their impact on the immune system and development of resistance. Also, there is a possibility that the HIV being measured is not capable of infecting other cells, possibly due to the effect of protease inhibitors. This may be why in the first study "blips" to levels of less than 200 copies did not result in increased failure. Another possibility is that these small "blips" in HIV replication may help stimulate an improved immune response to HIV, although this is mere speculation. The most important message from these studies is that if the viral load increases to only slightly above 50 copies, testing should be repeated prior to considering any change in therapy. The viral load should be followed closely to determine if the increase is merely a "blip," or if in fact it will soon be followed by a progressive increase in viral load, possibly necessitating a change in treatment.