Patients on HAART Often Have an Excess of Unintegrated HIV DNA: implications for monitoring reservoirs
Agosto LM, Liszewski MK, Mexas A et al. Virology 2010; Oct. 20, Pub. ahead of print.
It is thought that the majority of HIV DNA in treated patients is integrated since unintegrated HIV DNA appears to be unstable. In this paper, Una O'Doherty group in Philadelphia extend their findings previously published last summer in Vienna, showing that this is not always the case.
They evaluated total HIV DNA and integrated HIV DNA in PBMC from 7 closely monitored patients on suppressive HAART (for at least 1 year, EFV based regimen) and found an excess of total over integrated DNA in 3 cases. This observation implies that measurements of total HIV DNA do not always correlate to the level of integration, and could not be a suitable correlate of the reservoir size in some patients. Because unintegrated DNA has a short half life in vivo, this excess may represent new rounds of infection. Alternative explanations are the existence of undetected viral blips, or low levels of viral replication leading to the accumulation of 2-LTR circles over time prior to the initiation of therapy.
Based on these findings, the authors conclude that a measure of integrated HIV DNA is a better indicator of the reservoir size than total HIV DNA measurement. This method could also be employed for determining if novel drugs that target the reservoir, like HDACi, can decrease the level of integration over time.
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Key words: DNA, HAART, HIV, Proviral, Reservoir, Reservoirs, cure