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Background:  Treatment of HIV-1 infection with HAART can reduce viremia to below 50 copies of HIV-1 RNA/mL. However, a low level of virus production continues raising concerns regarding evolution of drug resistance. The present study determined whether drug resistance mutations could be detected in the plasma virus of these well-suppressed patients, and if so, to examine the significance of these mutations.  We describe longitudinal, clonal genotypic analysis of plasma virus from treated adults who had suppression of viremia to <50 copies/mL. 

Methods:  Genotypic analysis of plasma viral RNA from patients with viral loads below 50 copies/mL was carried out by a nested RT-PCR amplification strategy.  Using analytical approaches for distinguishing selected resistance mutations from non-selected mutations and PCR errors, we looked for resistance in the RT and protease genes. 

Results:  A total of 286 independent RT or protease clones were obtained from 8 HIV-1-infected adults who maintained suppression of viremia for up to 15 months. In patients with no history of prior non-suppressive therapy before starting HAART, no shared drug resistance mutations were detected. Sporadic resistance mutations were detected in some viral clones but were not fixed at subsequent times. In patients previously treated with nonsuppressive therapy, no new shared mutations developed and none of the existing mutations increased in frequency over the study period.

Conclusions:  The longitudinal nature of our study allowed insights into the dynamics of low-level viremia.  Despite ongoing low-level viremia, we did not detect accumulation of new mutations clearly attributable to the current, suppressive HAART in any of these well suppressed patients. In summary, our data suggests that in some patients on HAART, new cycles of replication are suppressed to a level that does not allow the evolution of drug resistance over a time frame of years.

Keywords: persistant viremia; drug resistance; genotype