Specific Redistribution Effect that Results in Increased

HIV entry inhibitors such as maraviroc (MVC) prevent cell-free viruses from 24 entering the cells. In clinical trials, patients who were treated with MVC often 25 displayed viral loads that were above the limit of conventional viral load detection 26 in comparison with efavirenz-based regminens. We hypothesize that viruses 27 blocked by entry inhibitors may be redistri buted to plasma where they artificially 28 increase viral load measurements in contrast to use of antiretroviral drugs 29 (ARVs) that act intracellularly. 30 We infected PM-1 cells with CCR5-tropi c HIV-1 BaL or CXCR 4-tropic HIV-1 NL4-31 3 in the presence of inhibitory concentrati ons of efavirenz, ralt egravir, enfuvirtide, 32 maraviroc, and AMD3100, the latter three being entry inhibitors. Supernatant 33 viral load, reverse transcriptase enzyme activity, and intracellular nucleic acid 34 levels were measured at times up to 24 hr post-infection. Infectivity of 35 redistributed dual-tropic HIV-1 wa s assessed using TZM-bl cells. 36 Extracellular viral load analysis revealed that entry inhibitor-treated cells had 37 higher levels of virus in supernatant versus the other ARVs at 8 hours post-38 infection. By 24 hours, supernatant viral load was still higher for entry inhibitors