More reasons to reexamine the definition of viral blip during antiretroviral therapy.

According to Webster’s Dictionary [1], a ‘‘blip’’ is a sudden minor shock or meaningless interruption. One of the earliest uses of this term in the human immunodeficiency virus (HIV) literature was by Wodarz and Nowak [2] in their conceptual HIV dynamics model that involved ‘‘the occurrence of ‘blips’ of such [CXCR4-tropic HIV] mutants, which rapidly go extinct.’’ Use of the term in the context of antiretroviral therapy (ART) became popular in the bygone era of limited ART options when the goal of therapy for many patients was maintenance of a stable CD4 T-cell count. In that era, a transient increase in plasma HIV-1 RNA load to levels #1000 copies/mL would have provoked little concern and been considered meaningless or inconsequential. There has since been dramatic improvement in the potency and tolerability of modern ART, making sustained levels of HIV-1 RNA ,50 copies/mL achievable for most patients. The sensitivity of qualitative and quantitative tools that can be used to interrogate subterranean virologic events is increasing, seemingly daily. Consequently, the magnitude of transient viremia that can be considered minor or inconsequential (ie, a blip) needs continual reexamination. In the elegant retrospective observational cohort study by Grennan et al, published in this issue of the Journal [3], viral blip was defined as a transient HIV-1 RNA increase to 50–999 copies/mL after attaining ,50 copies/mL during ART. The investigators achieved their objectives of (1) determining correlates of the transient HIV-1 RNA increases and (2) determining the impact on virologic rebound. Incidentally, their results also strengthen the need to narrow the definition of viral blip in clinical and research domains. A strength of Grennan et al’s study is the large number of HIV-12infected patients (N 5 4560) enrolled in the Canadian Observational Cohort through January 2009. From this cohort, Grennan et al identified a study population of 3550 patients with confirmed virologic suppression, defined as HIV-1 RNA ,50 copies/mL on 2 consecutive occasions at least 30 days apart. To avoid overestimating the incidence of transient viremia after suppression, $2 HIV-1 RNA increases to 50–999 copies/mL within a 30-day period were considered to be part of the same event. During a median observation period of 2.7 years, HIV-1 RNA was quantified a median of 11 times per patient, mirroring the practice in many clinical settings. Onequarter of the patients had .6 HIV-1 RNA tests per year, possibly reflecting additional testing that was done to evaluate measurements .50 copies/mL. Grennan et al confirmed that transient viremia of 50–1000 copies/mL occurs commonly during ART and tends to cluster between 50 and 200 copies/mL. In addition, using an adjusted multivariable model, they revealed that patients monitored with the ultrasensitive Roche Amplicor HIV-1 Monitor (version 1.5) assay, a polymerase chain reaction (PCR) amplification–based assay, experienced lower rates of transient viremia compared with those monitored using the branched DNA (bDNA) assay (Chiron Corp). Techniques for HIV-1 RNA quantification can be divided broadly into those based on signal amplification with bDNA and those utilizing nucleic acid amplification with PCR. Although the results with different assays tend to have acceptable correlation at relatively high HIV-1 RNA levels, interand intra-assay variability may be significant around the lower quantification limits. In general, PCR amplification platforms are more likely to report low-level viremia in samples with undetectable HIV-1 RNA by bDNA [4], making Grennan et al’s finding intriguing. Because each plasma sample was not concurrently Received and accepted 15 December 2011. Correspondence: Babafemi Taiwo, MBBS, Division of Infectious Diseases, Northwestern University, 645 N Michigan Ave, Suite 900, Chicago, IL 60611 (b-taiwo@ northwestern.edu). The Journal of Infectious Diseases 2012;205:1189–91 The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected] DOI: 10.1093/infdis/jis109