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One goal of antiretroviral therapy (ART) is to suppress viral replication completely, thereby preventing further viral evolution and resistance development. Viral-load testing technology has evolved over time and now allows for detection of <50 viral copies/mL. However, it is not clear whether the presence of virus at such low levels has any effect on the development of virologic failure.
In this retrospective study, researchers identified 1247 patients on ART who had a viral-load measurement of <50 copies/mL on a sensitive assay and at least 12 months of follow-up data subsequent to that measurement: 240 of the patients had baseline viral loads between 40 and 49 copies/mL (group A), 507 had detectable but not quantifiable levels of HIV RNA below 40 copies/mL (group B), and 500 had undetectable HIV RNA levels (group C).
The proportion of patients who experienced viral rebound to >50 copies/mL was 34.2% for group A, 11.3% for group B, and 4.0% for group C. The proportion with rebound to >400 copies/mL was 13.0%, 3.8%, and 1.2%, respectively. These associations were independent of adherence levels. No significant differences were seen in the proportion of patients who developed resistance mutations after rebound: 12 of 35 in group A, 9 of 21 in group B, and 2 of 7 in group C.
Doyle T et al. Plasma HIV-1 RNA detection below 50 copies/mL and risk of virologic rebound in patients receiving highly active antiretroviral therapy. Clin Infect Dis 2012 Jan 11; [e-pub ahead of print]. (http://dx.doi.org/10.1093/cid/cir936)
Gandhi RT and Deeks SG. Plasma HIV-1 RNA levels during antiretroviral therapy: How low is low enough? Clin Infect Dis 2012 Jan 11; [e-pub ahead of print]. (http://dx.doi.org/10.1093/cid/cir933)
Comment
Although this study was of a decent size, baseline differences between the groups made it difficult to compare outcomes. For instance, the amount of time spent with a viral load <50 copies/mL before baseline varied significantly (median, 0.2, 1.3, and 2.8 years for groups A, B, and C), and group A included substantially fewer patients with high-level adherence. Overall, though, the results appear biologically plausible and are consistent with other studies suggesting that the lower the viral load, the better the virologic outcome. However, we still do not know what these ultra-low levels of HIV RNA mean clinically and whether they should affect treatment decisions. Debate is ongoing, for instance, on whether minute amounts of HIV represent true viral replication or release of virions from dying lymphocytes. Furthermore, viremia can represent patient factors (adherence), viral factors (virulence), or drug factors (susceptibility), and these may each have very different implications for management.