Humanized Mice Recapitulate Key Features of HIV-1 Infection: A Novel Concept Using Long-Acting Anti-Retroviral Drugs for Treating HIV-1
Figure 1
PK data for 3TC, TDF, TMC278-LA and TMC181-LA.
(A and C) Plasma levels of 3TC and TDF, respectively, over a day of mice on food pellets containing 0.5 mg/g food of 3TC or TDF for 2 weeks. (B and D) Decay rate of 3TC (t½ = 5.5 h) and TDF (t½ = 3.5 h), respectively, when replacing the food containing 3TC or TDF with standard food. (E and F) Plasma levels after one dose of either TMC278-LA (160 mg/kg) or TMC181-LA (white dots: 200mg/kg; black dots: 400mg/kg) administered s.c. The data were obtained with mice on ART-containing food pellets for at least 2 weeks to permit PK equilibration. The shaded area in (A–D) indicates the therapeutic range as defined in humans [42], [43]. The dashed line in (E and F) indicates the target concentration (C target). Median effective concentration (EC) 50 values of TMC278 and TMC181 are 4.95 ng/ml and 1.29 ng/ml respectively in vitro in MT4 cells cultured with 50% human serum. The different colours indicate the experiments done with the same food batch, and whether we used mice transplanted with human CD34+ cells or not (White, red and yellow dots indicate humanized mice, green and blue dots indicate mice without transplantation of human CD34+ cells).