522   Low-Level HIV Viral Rebound and Blips in Patients Receiving Potent Antiretroviral Therapy.

G. Greub¹, A. Cozzi Lepri*², B. Ledergerber¹, S. Staszewski², L. Perrin¹, V. Miller², P. Francioli¹, H. Furrer¹, M. Battegay¹, P. Vernazza¹, E. Bernasconi¹, H. F. Günthard¹, B. Hirschel¹, A. N. Phillips², and A. Telenti¹.
¹The Swiss HIV Cohort Study (SHCS) and²The Frankfurt HIV Clin. Cohort.

Background:After achieving optimal HIV suppression while receiving antiretroviral therapy (ART), low-level viral rebound may represent early treatment failure or a transient increase in viral load, commonly described as a "blip". The outcome of the latter event remains undefined.

Methods:We analysed data on low level viral rebound (51 to 500 HIV RNA copies/ml) among 1858 patients achieving two consecutive viral loads <50 copies/ml. Patients were receiving potent ART and participated in the SHCS (n = 908) or Frankfurt (n = 950) cohort. After low-level viral rebound, a "blip" was defined as a viral load <50 copies/ml, and "sustained low level viral load" was defined as a persistent value between 51 and 500 copies/ ml. "Confirmed viral failure" was defined as two consecutive values >500 copies/ml.

Results:Low-level viral rebound was observed in 604 (32.5%) patients, an incidence of 37.4 episodes per 100 person-years. Blips were observed in 235 of 308 (76%) patients with rebound to 51—100 copies/ml and in 184 of 296 subjects (62.2%) with rebound to 101—500 copies/ml (p < 0.001). Following the initial four ultrasensitive determinations, incidence of confirmed viral failure was 5.1 per 100 person-years (95% CI, 3.9—6.5) for "optimally controlled subjects" (all four viral loads <50 copies/ml), 7.9 (3.4—15.7) for subjects with a blip, and 21.7 (9.4—42.7) for those with low-level sustained viral load. In Cox's regression models, hazard ratios of confirmed viral failure were 1.06 (0.37—3.00) for blip and 3.01 (1.15—8.28) for low-level sustained viral load compared to optimally controlled subjects.

Conclusions:Low-level viral rebound, blips, and episodes of sustained low-level viral load are frequent. While patients with early blips are not at increased risk of subsequent failure, episodes of sustained low-level viral rebound should be followed closely. These findings are relevant for decisions regarding practical management of low-level viral rebound and for improving understanding of residual viral replication in patients receiving potent ART.