Pre-exposure Prophylaxis Prevents Intravaginal HIV-1 Transmission in Humanized BLT Mice

<div><p>(A) Kaplan-Meier plot of the time course to plasma antigenemia conversion following intravaginal HIV-1 exposure in BLT mice with or without the 7-d pre-exposure regimen of FTC/TDF (administered once daily starting 48 h prior to intravaginal inoculation).</p> <p>(B) Plasma from the seven infected BLT mice and the five FTC/TDF + HIV-1 mice was tested for the presence of HIV-1 RNA. Data presented depict the initial positive viral RNA value for each mouse examined. The dashed line indicates the limit of detection for this assay.</p> <p>(C–E) Shown are the levels of human CD4⁺ (orange squares) and CD8⁺ (blue circles) T cells in peripheral blood as well as the levels of HIV p24 antigenemia (black triangles) in plasma for (C) naive control (<i>n</i> = 6), (D) HIV-1 infected (<i>n</i> = 7), and (E) pre-exposure FTC/TDF-treated animals (<i>n</i> = 5). In (D), note that in seven of eight tested BLT mice, a single exposure to HIV-1 led to intravaginal transmission and an initial drop, with subsequent stabilization, in the levels of peripheral blood CD4⁺ human T cells. In contrast, no changes were observed in either the naive control (C) or BLT mice that received FTC/TDF for pre-exposure prophylaxis (E). In (D) and (E), day 0 is the day of inoculation and is indicated by an arrow. Gating strategy for flow cytometric analysis: live cells → human CD45 → human CD3 → human CD4 or CD8.</p> <p>(F) Immunohistochemical staining for human CD4⁺ cells within the vagina of a representative FTC/TDF-treated mouse demonstrating the continued presence of CD4⁺ T cells in this tissue (left, bar indicates 50 μm; right, bar indicates 12.5 μm; box indicates region magnified in subsequent image).</p>