521 Viral Blips During HAART in Primary HIV Infection M. Di Mascio*1, M. Markowitz2, M. Louie2, C. Hogan2, V. Simon2, A. Hurley2, D. D. Ho2, A. S. Perelson1 1Los Alamos Natl Lab, NM and 2Aaron Diamond AIDS Res Ctr, New York, NY
Background: We previously reported that chronically HIV-1 infected patients (pts) have a higher tendency to show viral blips during HAART than pts treated during acute and early HIV infection (PHI), with this tendency being independent of the drug regimen.
Methods: We analyzed 68 pts in 6 prospective studies [LPV/RIT/TDF/EFV/3TC; RIT/SAQ/AZT/3TC; ABC/APV/AZT/3TC; IND/AZT/3TC; RIT/AZT/3TC; ABC/APV/3TC]. All pts were naïve to HAART, treated within 6 months (mos) from the onset of symptoms of acute infection and achieved viral load (VL) suppression below 50 copies/ml. A viral blip is defined as any value of VL over 50 copies/ml and below 1000 copies/ml during the period of suppression. Pts were observed from the time they reached VL suppression for a mean period of 2 years and a mean number of 23 ±11VL measurements. Baseline, pre-treatment genotypic drug resistance testing was available for all pts.
Results: The mean viral blip frequency (VBF) per pt was 0.07 ±0.09/sample, with 40% of pts showing no blips. The mean blip amplitude was 133 ±101 HIV-RNA copies/ml. VBF did not change with longer times of observation. A positive correlation was observed between VBF and viral load at the start of therapy (V0) (r = 0.48, P = 1.0 x 10-5). Ten percent (10%) of the pts studied were found to have viruses with resistance-associated mutations. In 3 cases, drug resistance reduced the number of active compounds included in the regimen. In the 4 other pts only secondary resistance mutations were detected. No association was found between baseline drug resistance and VBF during the period of suppression. A parametric analysis where both V0 and the time from the onset of symptoms to the start of therapy were taken into account, reveals that in pts who started therapy later, for which the baseline viral load is more indicative of the set-point they would reach if left untreated, the baseline VL is a significant predictor of VBF during treatment.
Conclusions: Viral blip frequency in pts successfully treated with HAART during acute or early infection is not associated with baseline drug resistance. Pts showing higher viral blip frequencies are probably the ones who would achieve higher viral load set-points if they were left untreated, which has been proposed as an important predictor of disease progression. This suggests that VBF is determined, at least partially, by factors that precede the period of treatment.
