FIG 1.
I-BET151 treatment activates HIV-1 reservoirs under suppressive cART in vivo. (A) Pharmacokinetics/pharmacodynamics of I-BET151 in NSG mice. NSG mice were treated with 18 mg/kg of I-BET151 through gavage, and drug concentration in blood was measured by high-performance liquid chromatography (HPLC). (B to D) Humanized mice were infected with HIVJR-CSF. cART was initiated at 13 wpi. BETi treatment was initiated at 21 wpi by daily gavage (18 mg/kg) until termination at 22.3 wpi. (B) HIV plasma load. (C) Relative cell-associated viral RNA levels in human cells of lymphoid tissues (spleen [SP], bone marrow [BM], liver [LV], and lung [LU]), normalized to human CD4 mRNA level. (D) Cell-associated HIV-1 DNA copies in human cells in different tissues (spleen, bone marrow, liver, and lung) were measured by real-time PCR. Bars in dot graphs indicate mean values. *, P < 0.05.