Article Figures & Data
Figures
- FIG. 1.
Computer simulation of a 500-mg oral dose. Multidose pharmacokinetic data were modeled using the programs in the ADAPT II software package. The points are the computer-simulated weighted means for the patient population. The AUC24 for the 500-mg dose was determined to be 10.08 mg · h/liter. (A) Simulated profile for 500 mg administered once daily. (B) Simulated profile for 250 mg administered q12h.
- FIG. 2.
Comparison of the efficacy of abacavir on cell infection of CEM cells with HIV strains IIIB and MN versus cocultivation of CEM cells with HIV-infected H9 cells at a 100:1 ratio. The dose of drug was 0.42 μg/ml, which was the calculated value for a constant exposure of cells to the simulated 500-mg dose. HIV p24 was measured in cell supernatants of the cultures at day 7 postinfection.
- FIG. 3.
(a) Effect of abacavir on the spread of HIV strain IIIB. Three bioreactors were set with 3 × 107 CEM cells and 3 × 105 H9 IIIB cells (1:100 I/u). One hollow-fiber bioreactor was exposed to the calculated constant infusion level of a 500-mg dose (0.42 μg/ml abacavir) (▴). The second was exposed to a simulated 500-mg q24h dose (•) using the computer-driven pump to simulate an oral dose. The third was an untreated unit (▪) that was continuously exposed to medium without drug. Samples were taken at the indicated time points, and p24 was measured as indicated. (b) Effect of abacavir on the spread of HIV strain MN. Three bioreactors were set with 3 × 107 CEM cells and 3 × 105 H9 MN cells (1:100 I/u). One hollow-fiber bioreactor was exposed to the calculated constant infusion level of a 500-mg dose (0.42 μg/ml abacavir) (▴). The second was exposed to a simulated 500-mg q24h dose (•) using the computer-driven pump to simulate an oral dose. The third was an untreated unit (▪) that was continuously exposed to medium without drug. Samples were taken at the indicated time points and p24 was measured as indicated. (c) Effect of the schedule on the ability of the same total exposure of abacavir (AUC24 = 10.0838 mg·h/liter) on the spread of HIV strain MN. Three bioreactors were set with 3 × 107 CEM cells and 3 × 105 H9 MN cells (1:100 I/u). One hollow-fiber bioreactor was exposed to the 250-mg q12 dose (▪). The second was exposed to a simulated 500-mg q24h dose (▴) using the computer-driven pumps to simulate an oral dose. The third was an untreated unit (•) that was continuously exposed to medium without drug. Samples were taken at the indicated time points, and p24 was measured as indicated.
- FIG. 4.
Examination of the effect of no therapy and abacavir (300 mg q12h, 600 mg q24h, and 1,200 mg q48h) on the spread of HIV strain HXB-2. Samples for p24 analysis were from cell supernatant fluid from the ECS of individual hollow-fiber units and frozen at −70°C until the samples were taken at the 15- and 30-day points. At day 15 and day 30 samples from each hollow fiber were thawed, diluted, and tested in a p24 antigen capture enzyme-linked immunosorbent assay. The means of two determinations and the SDs are plotted on a linear scale.
