HIV drug resistance detected during low-level viraemia is associated with subsequent virologic failure.

Many patients on antiretroviral therapy experience episodes of low-level viremia (LLV), commonly defined as viral loads between 50 and 1000 HIV-RNA copies/mL [1]. Since many treatment guidelines define virologic success as maintaining viral loads below the limits of assay detection [2–5], LLV can be a concern for both physicians and patients. Resistance testing has been shown to be an effective predictor of future virologic failure in a number of studies [6–9]. However, most commercial resistance assays can only be performed on samples with viral loads above a minimum of 500-2000 copies/mL [10,11]. Despite this, in-house resistance assays can be performed on samples with low-level viraemia below 1000 copies/mL [12–14], and the success rate of such testing has increased over time in some settings [15]. Indeed, several studies have found that LLV is associated with subsequent virologic failure, immune activation, inadequate CD4 recovery, and development of drug resistance [16–21], and that resistance can be detected at LLV [22–24]. However, there is limited evidence that risk of virologic failure after LLV can be further elevated by the presence of resistance. Intriguingly, however, two recent studies on a modest number of individuals indicated that LLV resistance may be associated with virologic failure [25,26]. In British Columbia, Canada, resistance testing on LLV samples has been performed since approximately 2000. Starting in 2004, the results of resistance testing on LLV samples were made available to the ordering physician prospectively. We undertook the present analysis to evaluate the impact of emergent HIV drug resistance at LLV on the risk of subsequent virologic failure.