At the Workshop AMJ Wensing (University Medical Centre, Utrecht, The Netherlands) reported on a study regarding the association between viral load "blips" above detection and resistance and viral load rebound. In patients who achieve plasma HIV RNA <50 copies/ml during HAART, transient relapses ("blips") of the plasma viral load to levels above 50 copies/ml are regularly observed in some individuals. The goal of this study was to determine the mechanisms underlying these transient relapses of the plasma (blood) viral load during HAART.

Fifteen patients with a transient viral load relapse during HAART (3 or 4 drugs) were selected. The regimens of all patients included 3TC. All patients achieved viral load <50 copies/ml prior to relapse. Using an ultra-sensitive sequencing approach, the presence of resistance mutations was determined at the moment of relapse in both the protease and RT genes. The PCR product was sequenced according to the Big-dye-terminator protocol (Perkin-Elmer). Sequence analysis was performed using the ABI automated sequencer.

The median plasma viral load at the time of relapse was 72 copies/ml (range 50-1253). The genotype of the HIV plasma virus could be determined in 11 of the 15 patients. Primary mutations NRTI, NNRTI or protease inhibitors were seen conferring resistance to 1 or more of the administered drugs were observed in 8 of 11 patients, all of whom had the M184 3TC mutation in thr RT gene. Some of the 8 patients were treatment naÔve and some were experienced prior to the regimen they were taking at the time of this study. The median duration of follow-up after the relapse was 12 months. Failure of HAART defined as plasma levels above 50 copies/ml ocurred in only one patient after the transient relapse. Some patients were treatment naive and some were not.

The authors concluded that 2 mechanisms account for the blips during HAART. In approximately half of the cases resistant viruses are selected, indicating that viral replication occurred due to incomplete suppression, probably caused by a temporary decrease in the active drug concentrations. In the remaining cases, blips were due to the production of wild-type viruses most likely caused by activation of pre-therapy infected memory cells. In both cases a transient relapse of the plasma viral load did not preclude successful inhibition of viral replication <50 copies/ml by HAART therapy for at least 1 year after the relapse. As I previously mentioned, I spoke with one of the authors of this study and additional researchers. Their instinct was that viral load might rebound given enough time. I think the question is not answered until individuals are followed for a much longer period of time.