Modest deviations from optimal adherence to antiretroviral therapy promote residual HIV-1 replication in the absence of virological rebound in plasma

Alexander O Pasternak,Marijun De Bruin,Jan M Prins,Vladimir V Lukashov,Suzanne Jurriaans,Margreet Bakker,Ben Berkhout

doi:10.1186/1742-4690-8-s2-o35

Alexander O Pasternak, Marijun De Bruin + Show 5 more

Open Access

https://doi.org/10.1186/1742-4690-8-s2-o35

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Journal: Retrovirology	Publication Date: Oct 3, 2011
Citations: 5	License type: CC BY 2.0

Affiliation: Academic Medical Center, University of Amsterdam

Abstract

Background Modern antiretroviral therapy (ART) is assumed to allow a certain degree of nonadherence while still maintaining complete suppression of viral replication (forgiveness”), as virological suppression, measured by the commercial plasma viral load assays, is common at adherence levels >55-70% [1]. Yet, it is unknown whether HIV-1 replication is completely suppressed at these levels of adherence. [2]Here we investigated whether modest nonadherence to ART influences levels of HIV-1 RNA and DNA in peripheral blood mononuclear cells (PBMC).

Highlights

Modern antiretroviral therapy (ART) is assumed to allow a certain degree of nonadherence while still maintaining complete suppression of viral replication ("forgiveness”), as virological suppression, measured by the commercial plasma viral load assays, is common at adherence levels >55-70% [1]
Materials and methods Levels of HIV-1 unspliced RNA and viral DNA were quantified by seminested real-time PCR [2,3,4] in peripheral blood mononuclear cells (PBMC) of 40 HIV-infected patients who had been on successful ART for a median of 3.8 years before the start of the study and with good immune reconstitution
As ART only blocks the infection of new cells, but not viral RNA transcription in infected cells, the observed effect of decreased ART pressure on HIV RNA levels in PBMC strongly suggests new replication cycles despite ART, and not enhanced HIV-1 transcription in cells infected prior to therapy initiation

Summary

Background

Modern antiretroviral therapy (ART) is assumed to allow a certain degree of nonadherence while still maintaining complete suppression of viral replication ("forgiveness”), as virological suppression, measured by the commercial plasma viral load assays, is common at adherence levels >55-70% [1]. It is unknown whether HIV-1 replication is completely suppressed at these levels of adherence. [2]Here we investigated whether modest nonadherence to ART influences levels of HIV-1 RNA and DNA in peripheral blood mononuclear cells (PBMC) It is unknown whether HIV-1 replication is completely suppressed at these levels of adherence. [2]Here we investigated whether modest nonadherence to ART influences levels of HIV-1 RNA and DNA in peripheral blood mononuclear cells (PBMC)

Materials and methods

Conclusions

Shuter J