Raltegravir blocks the infectivity of red-fluorescent-protein (mCherry)-labeled HIV-1 _JR-FL in the setting of post-exposure prophylaxis in NOD/SCID/Jak3 ^−/− mice transplanted with human PBMCs

Employing NOD/SCID/Jak3 ^−/− mice transplanted with human PBMCs (hNOJ mice) and replication-competent, red-fluorescent-protein (mCherry; mC)-labeled HIV-1 _JR-FL (HIV _mC ), we examined whether early antiretroviral treatment blocked the establishment of HIV-1 infection. The use of hNOJ mice and HIV _mC enabled us to visually locate infection foci and to examine the early dynamics of HIV _mC infection without using a large amount of antiretroviral unlike in non-human primate models. Although when raltegravir (RAL) administration was begun 1 day after intraperitoneal (ip) inoculation of HIV _mC , no plasma p24 or plasma HIV-1-RNA (pRNA) were detected in 10 of 12 hNOJ (hNOJ _mC ^RAL+ ) mice as assessed on the last day of the 14-day continuous twice-daily RAL administration, all 10 untreated hNOJ _mC (hNOJ _mC ^RAL− ) mice became positive for p24 and pRNA and had significantly swollen lymph nodes in peritoneal cavity and abundant p24 ⁺ /mC ⁺ /CD3 ⁺ /CD4 ⁺ T cells and p24 ⁺ /mC ⁺ /CD68 ⁺ monocytes/macrophages were identified in their omenta and mesenteric lymphoid tissues/lymph nodes upon necropsy of the mice on day 14. In 12 hNOJ _mC ^RAL+ mice, no significantly swollen lymph nodes were seen compared to hNOJ _mC ^RAL− mice; however, in the omentum of the 2 hNOJ _mC ^RAL+ mice that were positive for pRNA and in site RNA, mC ⁺ /p24 ⁺ /CD3 ⁺ /CD83 ⁺ cells were identified, suggesting that viral breakthrough occurred later in the observation period. The present data suggest that the use of hNOJ mouse model and HIV _mC may shed light on the study of early-phase dynamics of HIV-1 infection and cellular events in post-exposure/pre-exposure prophylaxis.