Titanji, BK;
Pillay, D;
Jolly, C;
(2017)
Combination Antiretroviral Therapy (cART) and Cell-cell spread of Wild-type and Drug-Resistant HIV-1.
Journal of General Virology
, 98
pp. 821-834.
10.1099/jgv.0.000728.
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Abstract
HIV-1 disseminates between T cells either by cell-free infection or by highly-efficient direct cell-cell spread. The high local multiplicity that characterizes cell-cell infection causes variability in the effectiveness of antiretroviral drugs applied as single agents. Whereas Protease Inhibitors (PIs) are effective inhibitors of HIV-1 cell-cell and cell-free infection, some Reverse Transcriptase Inhibitors (RTIs) show reduced potency; however antiretrovirals are not administered as single agents and are clinically used as combination antiretroviral therapy (cART). Here we explored the efficacy of PI and RTI-based cART against cell-cell spread of wild-type and drug-resistant HIV-1 strains. Using a quantitative assay to measure cell-cell spread of HIV-1 between T cells, we evaluated the efficacy of different clinically relevant drug combinations. We show that combining PIs and RTIs improves the potency of inhibition of HIV-1 and effectively blocks both cell-free and cell-cell spread. Combining drugs that alone are poor inhibitors of cell-cell spread markedly improves HIV-1 inhibition, demonstrating that clinically relevant combinations of ART can inhibit this mode of HIV-1 spread. Furthermore, comparison of WT and drug-resistant viruses reveals that PI and RTI resistant viruses have a replicative advantage over wild-type virus when spreading by cell-cell means in the presence of cART, suggesting that in the context of inadequate drug combinations or drug resistance, cell-cell spread could potentially allow for ongoing viral replication.
| Type: | Article |
|---|---|
| Title: | Combination Antiretroviral Therapy (cART) and Cell-cell spread of Wild-type and Drug-Resistant HIV-1 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1099/jgv.0.000728 |
| Publisher version: | http://dx.doi.org/10.1099/jgv.0.000728 |
| Language: | English |
| Additional information: | This is an open access article published by the Microbiology Society under the Creative Commons Attribution License |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1540040 |
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