The importance of HIV RNA detection below 50 copies per mL in HIV-positive patients on antiretroviral therapy: an observational study

Abstract

BackgroundSuppression of plasma HIV viral load to less than 50 copies per mL is associated with durable clinical and immunological benefits and is the recommended goal of antiretroviral therapy (ART). Currently available viral load assays can detect HIV RNA below this threshold but the importance of low-level detection is unclear. We aimed to determine whether HIV RNA detection below 50 copies per mL is associated with an increased risk of virological rebound in ART-treated patients. Methods1247 HIV-positive patients on ART with viral load less than 50 copies per mL at a single arbitrary timepoint as measured by RealTime PCR (Abbott, Maidenhead, UK) were stratified by the clinically unreported viral load into three groups: 40–49 copies per mL (RNA40–49), less than 40 copies per mL but not quantifiable (RNA+), and not detected (RNA−). Virological outcomes over the following 12 months were analysed. Time to viral load rebound according to baseline viral load category was assessed and the factors associated with rebound were identified in a Cox proportional hazards model incorporating baseline viral load, clinical and demographic data, and adherence levels. FindingsOver 12 months of follow-up the proportion of patients experiencing viral load rebound of more than 50 copies per ml in the RNA40–49, RNA+, and RNA–groups were 34·2% (82/240), 11·3% (57/507), and 4% (20/500), respectively. For viral rebound of more than 400 copies per mL the proportions were 13% (31/240), 3·8% (19/507), and 1·2% (6/500), respectively. After multivariate adjustment, the hazard ratio for rebound of more than 400 copies per mL was 6·91 (95% CI 2·90–16·47, p<0·0001) for baseline RNA40–49 and 2·88 (1·24–6·69, p<0·0001) for baseline RNA+. Baseline viral load category predicted rebound independently of adherence levels. InterpretationIn ART-treated HIV-positive patients, detection of viral load between 40 and 49 copies per mL and less than 40 copies per mL (as measured by RealTime PCR) is associated with an increased risk of virological failure. The currently recommended goal of ART of 50 copies per mL might be suboptimal and might need to be revised to a lower cut-off. FundingRoyal Free Hospital NHS Trust, European AIDS Treatment Network.