Many patients on highly active antiretroviral therapy with undetectable levels of HIV-1 RNA experience viral load blips. True periods of detectable viremia raise concerns that regimen potency is inadequate to suppress viral replication completely, which could lead to the development of resistance. Because blips are not associated with long-term clinical or virological failure in most studies, there is uncertainty over their clinical significance.
Recent data help explain the lack of association between blips and clinical or virological failure. Many blips are not an actual rise in viral load, but instead represent normal biological fluctuations around a mean viral load below 50 copies/ml as well as statistical variations around the detection limit of the viral load assay. Some blips may also result from laboratory processing artefacts. Therefore, most blips are not reproducible on duplicate viral load measurements. With frequent viral load measurements, there is less correlation between blips and demographic, treatment, or HIV-associated clinical factors than previously reported. Likewise, many blips are often unrelated to intercurrent illnesses, vaccination, non-adherence, or decreases in antiretroviral drug concentrations. Most importantly, new genotypic resistance mutations do not develop before, during, or immediately after most blips.
Despite recent findings suggesting that many blips are laboratory or statistical aberrations, it remains important to differentiate blips from early virological failure or persistent detectable low-level viremia. Once the episode of detectable viremia is clearly defined as a blip, however, there should be no cause for clinical concern.
Departments of Medicine, Johns Hopkins University School of Medicine, Baltimore Maryland, USA
Correspondence and requests for reprints to Richard E. Nettles, Bristol Myers Squibb, MS E12-16 PO Box 4000, Princeton, NJ 08543, USA Tel: +1 609 252 3719; fax: +1 609 252 7034; e-mail firstname.lastname@example.org
Sponsorship: This study received financial support from NIAID grants K08 AI060367 (to R.E.N.).
☆Current affiliations: R.E.N. is currently employed by Bristol Myers Squibb; T.L.K. is currently employer by Vertex Pharmaceutic.