Viral Blips and Virologic Failure

Intermittent episodes of low-level viremia (viral load "blips") are often observed in people on highly active anti-retroviral therapy (HAART) with a suppressed viral load (HIV RNA below 50 copies). An increased frequency of blips is associated with a slower fall in the viral load (VL) and an increase in the number of viral mutations, but as of yet viral blips have not been associated with subsequent virologic failure (Abstract 532).

Dr. Diane Havlir has previously published in JAMA that VL blips do not predict virologic failure in people with limited or no prior antiretroviral experience. At the Ninth Retrovirus Conference, Dr. Havlir analyzed two ACTG salvage therapy trials to determine whether blips in the VL are associated with virologic failure in antiretroviral-experienced people (Abstract 93). A viral blip was defined as a VL of more than 50 copies in a patient who was previously suppressed, followed by a subsequent VL of less than 50 copies. Virologic failure was defined as two consecutive measures of VL above 200 copies.

In ACTG 398, 25 percent of people who had a VL below 50 copies were observed to have at least one blip. The median blip was 81 copies, and only 7 of the 41 people had blips in their VL over 500 copies. The CD4+ cell count at 48 weeks was similar in subjects who did and did not experience blips. Viral blips also were not associated with baseline drug resistance or virologic failure. Virologic failure was, on the other hand, associated with the failure to suppress HIV DNA to below 50 copies and drug treatment interruptions. Similar results were observed in the other salvage therapy trial, ACTG 359. These two studies demonstrate that highly treatment-experienced subjects can tolerate blips without HIV progression. Treatment changes are, therefore, not always necessary for transient low-level viremia, since blips in the VL is not synonymous with virologic failure. However, trials with longer follow-up are necessary to better clarify the significance of these observed viral blips.

M. Di Mascio analyzed the dynamics of viral blips during HAART therapy in 123 previously treatment-naïve people (Abstract 94). More than 75 percent of the participants had at least one blip during the period of observation, with a mean of 165 copies. People were found to have different tendencies to have viral blips and the frequency of an individual to blip over time remained constant. People who had more consecutive blips also had a higher frequency of blips overall. Two consecutive blips are thought more likely to represent two independent episodes of incomplete viral suppression rather than one prolonged period with increased viremia.

In conclusion, the authors felt that viral blips were not associated with the amount of time on HAART and therefore could not be explained by a decrease in drug adherence rates as was originally thought. Although viral blips should probably still spark discussions about drug adherence, it appears that they represent a random process that can occur even if people are completely adherent to their HAART regimen. New theories behind the causes of these blips were subsequently proposed. These blips may be a result of variable drug concentrations in the blood over time or periods of immune activation that stimulate HIV replication. Di Mascio speculated that the "intermittent viremic episodes might reflect a random, massive release of HIV virions (viruses) from one compartment [within the body], followed by transport to another [compartment] where they are more quickly cleared."

Dr. Lara Strick is a member of STEP's Board of Directors, and is completing her residency in internal medicine at the University of Washington.