RT Journal Article SR Electronic(1) A1 Titanji, Boghuma Kabisen A1 Pillay, Deenan A1 Jolly, ClareYR 2017 T1 Combination antiretroviral therapy and cell–cell spread of wild-type and drug-resistant human immunodeficiency virus-1 JF Journal of General Virology, VO 98 IS 4 SP 821 OP 834 DO https://doi.org/10.1099/jgv.0.000728 PB Microbiology Society, SN 1465-2099, AB Human immunodeficiency virus-1 (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 used clinically 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 wild-type 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., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000728