Abstract
In most HIV-infected individuals adherent to modern antiretroviral therapy (ART), plasma viremia stays undetectable by clinical assays and therefore, additional virological markers for monitoring and predicting therapy responses and for measuring the degree of HIV persistence in patients on ART should be identified. For the above purposes, quantitation of cell-associated HIV biomarkers could provide a useful alternative to measurements of viral RNA in plasma. This review concentrates on cell-associated (CA) HIV RNA with the emphasis on its use as a virological biomarker. We discuss the significance of CA HIV RNA as a prognostic marker of disease progression in untreated patients and as an indicator of residual virus replication and the size of the dynamic viral reservoir in ART-treated patients. Potential value of this biomarker for monitoring the response to ART and to novel HIV eradication therapies is highlighted.
Highlights
The concentration of free virus particles in blood plasma, represented by the copy number of virion RNA per milliliter of plasma, which can be reliably quantified by PCR methods, is traditionally used as the biomarker of HIV-1 replication [1,2,3]
A similar conclusion can be drawn from the analysis, by the same authors, of CA HIV RNA in lymphoid tissues of patients on antiretroviral therapy (ART) [111]. These results seem to contradict the earlier work of Hockett et al that estimated, using in situ hybridization (ISH) and quantitative PCR methods, that the vast majority of CA HIV RNA in lymphoid tissue of patients on suppressive ART is contained within a few cells with an RNA copy number per cell similar to that in untreated patients (>3 log10 copies/cell) [57], suggesting that these cells are productively infected
We have demonstrated, by seminested real-time PCR, that higher levels of HIV-1 usRNA in peripheral blood mononuclear cells (PBMC) are predictive of future therapy failure in patients on ART with undetectable plasma viremia [70]
Summary
The concentration of free virus particles in blood plasma (plasma viremia or plasma viral load), represented by the copy number of virion RNA per milliliter of plasma, which can be reliably quantified by PCR methods, is traditionally used as the biomarker of HIV-1 replication [1,2,3]. This seminested real-time PCR assay allows routine detection and quantitation of HIV RNA and DNA in the vast majority of PBMC samples of patients on combination ART with undetectable plasma viremia [69,70].
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