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Measuring below the bar: what is it telling us?

While sustained suppression of plasma HIV-1 RNA below the limits of detection with standard assays is possible in many infected individuals, it is clear that virus still persists in cellular reservoirs for prolonged periods of time [1,2]. Nevertheless, there is little evidence that viral evolution is occurring in this reservoir or that it will be a source of drug resistant virus in the future [2]. In addition to the cellular reservoir, other pharmacologically privileged areas such as the central nervous system and the genital tract may act as an additional sources of residual virus in those with ’undetectable’ levels of plasma HIV-1 RNA. Several groups have reported data using investigational assays that measure plasma HIV-1 RNA levels below 50 copies/ml, showing that many patients on potent antiretroviral (ARV) therapy have detectable levels present below the limits of detection of standard assays [3,4]. It is not yet known what the clinical implications are of having quantifiable viral levels in this range or what is the source of this low level viremia. Defining these issues may have implications in the clinic as well as towards our understanding of HIV-1 pathogenesis. In fact, recent investigation of novel ARV treatment strategies has provided insight into these areas of interest.