Low-level viraemia on HAART: significance and management

The source, significance and optimal management of low-level viraemia during highly active antiretroviral therapy (HAART) are poorly defined. This review highlights recent observations that have implications for clinical practice.

The definition of low-level viraemia remains elusive. Whereas evidence obtained with second-generation viral load assays indicates that confirmed detection of plasma HIV-1 RNA above 50  copies/ml predicts negative outcomes, third-generation assays detect HIV-1 RNA below this threshold. In patients monitored with the Abbott RealTime assay, the cutoff that should trigger confirmation of viraemia and clinical review can be revised to 40  copies/ml. Further data are needed on the cost-effectiveness of intervening when RNA detection is observed below this cutoff. Discrepancies among viral load assays prevent generalization of these observations. To further compound the issue, most patients on stably suppressive HAART show residual viraemia at around 1-10  copies/ml using research-based ultrasensitive assays. The source of residual viraemia remains controversial, but neither short nor long-term HAART intensification with antiretrovirals such as raltegravir reduces the viraemia. A transient effect of intravenous immunoglobulin has been reported, and different regimens may vary in their propensity to allow HIV-1 RNA persistence. Further studies are required to clarify the relationship between low-level viraemia and the size of proviral DNA reservoirs, and the contribution of cellular and tissue compartments and cell-to-cell spread to ongoing virus replication during HAART.

Understanding the source and clinical significance of HIV-1 RNA persistence in plasma during HAART is required to guide patient care and inform the design of HIV eradication strategies.