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Session 90 Poster Abstracts
Evolution of Drug Resistance
Wednesday, 1:30 - 3:30 pm
Poster Hall


651    
Frequency, Magnitude, Duration, and Genotypic Characterization of Intermittent Viremia ("blips") in Patients with Sustained Suppression of Plasma HIV-1 RNA
T Kieffer*1, R Nettles1, T Quinn1,2, B Jackson1, J Cofrancesco1, J Gallant1, D Persaud1, and R Siliciano1,3
1Johns Hopkins Univ. Sch. of Med., Baltimore, MD, USA; 2NIAID, NIH, DHHS, Bethesda, MD, USA; and 3Howard Hughes Med. Inst., Baltimore, MD, USA

Background:  Treatment of HIV-1 infection with HAART can reduce viremia to below 50 copies of HIV-1 RNA/mL. However, many patients on HAART occasionally have higher measurements, or blips, following which virus levels fall back below 50 copies/mL. There is evidence that patients who experience blips have higher levels of viral replication leading to concerns about the emergence of drug resistance. The nature of this intermittent viremia and the long-term consequences of blips on viral suppression have not been established.  Here, we determine the frequency, magnitude, and duration of blips in 10 well-suppressed patients on HAART by monitoring viral loads 3 times a week over a period of 3 months.  The presence of drug resistance during these blips is determined by genotypic analysis before, during, and after a blip. 

Methods:   Viral RNA from the plasma of well suppressed patients on HAART is quantified using the ultrasensitive Roche Amplicor Monitor System (detection limit of 50 copies/mL), in 2 independent laboratories.  Genotypic analysis was carried out by nested RT-PCR which amplified regions of the protease and RT genes.  Sequences were analyzed for known drug resistant mutations using the Los Alamos HIV Sequence Database of drug resistance mutations.

Results:  Blips were detected in the majority of the patients, with a mean magnitude of 57 copies/mL (range = 53 to 61).  The duration of all the blips detected was <48 hours.  Genotypic analysis showed no new drug resistant mutations.

Conclusions:  Our results suggest that most, but not all, patients experience intermittent viremia in a setting of sustained suppression on HAART. Frequent sampling has allowed delineation of the magnitude and duration of blips. Genotypic analysis both during and after the blip shows no emergence of new resistance, suggesting that these episodes of viremia above 50 copies/mL do not necessarily result from partially resistant virus.  In summary, patients may experience blips without evolution of drug resistance.

Keywords: blips; drug resistance; genotype