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Figure 4 | Retrovirology

Figure 4

From: The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study

Figure 4

Synergistic inhibition of HIV-1 RT by TFV-DP+FTC-TP combination analyzed by different methods. (A) The median-effect analysis where the solid line presents curve fitting of the CI values as a function of the fractional effect. The red line at CI = 1 represents additivity. The dashed lines represent 95% confidence interval. TFV-DP and FTC-TP are combined at 1:1 IC50 ratios (1:10 molar ratios) with an average CI value of 0.47; (B) The isobologram analysis where the diagonally drawn solid line (in red) represents additivity. Average deviation from dose-wise additivity was -0.43 (p = 0.001), indicating a synergistic effect of the combination; (C) The Berenbaum combination indices analysis where the open circles are data from five experiments and the solid line represents the CI line. The red bar at the CI50 indicates the 95% confidence intervals. The bar is to the left of the CI50 = 1 line, indicating synergy for this combination. In this experiment, TFV-DP and FTC-TP were combined at 1:4 IC50 ratios (1:40 molar ratios); (D) The Yonetani-Theorell plot where FTC-TP was tested as the "first drug" and TFV-DP was added as the "second drug" at the following concentrations: (black circle) 0 μM, (open circle) 0.1 μM, (black triangle) 0.2 μM, (open triangle) 0.4 μM, (black square) 0.8 μM, and (open square) 1.6 μM. The Yonetani-Theorell plot shows the lines are converging at the left of the y-axis and the slopes of the lines increased with TFV-DP concentration, indicating the combination was synergistic.

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