Nanoformulations of Rilpivirine for Topical Pericoital and Systemic Coitus-Independent Administration Efficiently Prevent HIV Transmission
Fig 4
Ability of RPV LA to offer coitus-independent protection from vaginal HIV-1 transmission in BLT mouse.
(A) Longitudinal analysis of RPV levels in plasma of NSG mice injected intramuscularly once with 7.5 mg or 15 mg RPV LA (n = 4 for each group, dotted line indicates IC90). (B) Plasma viral RNA in BLT mice challenged vaginally with HIV-1CH040 (3.5×105 TCID), a transmitted/founder virus 1-week post administration of RPV LA (15 mg, n = 6) or vehicle (n = 6) intramuscularly. Shown are plasma viral RNA (dotted line-LOQ 400 copies of RNA per ml of plasma). (C) Kaplan-Meier plots representing the percentage of BLT mice protected from HIV transmission by RPV LA as a function of the number of weeks post challenge until the first peripheral blood viral RNA detection. Protected animals were negative for viral RNA in plasma and viral DNA in tissue analyzed after necropsy (P = 0.0047, Log rank/Mantel Cox test). (D). Human CD45 cell levels in peripheral blood (percent of total live cells) and human CD4 levels (percent of human CD3 positive cells) were analyzed by flowcytometry at the indicated times. Solid lines: RPV LA treated mice, dashed lines: control animals.