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1.
Figure 2

Figure 2. From: Therapeutic Response to Peg IFN-alpha-2b and Ribavirin in HIV/HCV Co-infected African American and Caucasian Patients as a function of HCV Viral Kinetics and Interferon Pharmacodynamics.

Non-linear fitting of the viral load data (red circles) and the IFN concentration data (white triangles) by a pharmacodynamical model (solid lines, Eqs 1–6) for each individual patient (given here for 4 representative cases each for a different therapeutic response group). Note that the transient rebound in viremia at days 3–7 (and 10–14) are due to the decline in the IFN levels below the Ec90 threshold (dashed horizontal line). This non-linear fitting allowed us to obtain individual estimates for the pharmacodynamical parameters Ec90 (or Ec50) and Nhill.

L Rozenberg, et al. AIDS. ;23(18):2439-2450.
2.
Figure 3

Figure 3. From: Therapeutic Response to Peg IFN-alpha-2b and Ribavirin in HIV/HCV Co-infected African American and Caucasian Patients as a function of HCV Viral Kinetics and Interferon Pharmacodynamics.

Pharmacokinetic (PK) and pharmacodynamic (PD) parameters for individual patients given as function of race and therapeutic response. No difference in the IFN max concentration (Cmax, A) or in the IFN half-life (B) is observed between any of the groups. Ec50 (B) is significantly (P<0.03) higher for African-Americans as compared to Caucasians but is not predictive of therapeutic response. Nhill (F) is slightly but not significantly higher for African-American vs Caucasians. The combined PK/PD measures – Cmax/Ec90 (E) and days IFN level is above Ec90 during the first week (F) – are higher for Caucasians relative to African-Americans and are predictive of SVR. For comparison sake we also show here the parameters values obtained from our analysis of the data obtained for HCV mono-infected Caucasians treated with pegylated-interferon-a 2b 1.0 mg/kg [35]. Mono-infected patients show better Cmax/Ec90 properties than co-infected patients.

L Rozenberg, et al. AIDS. ;23(18):2439-2450.
3.

Figure 1. From: Therapeutic Response to Peg IFN-alpha-2b and Ribavirin in HIV/HCV Co-infected African American and Caucasian Patients as a function of HCV Viral Kinetics and Interferon Pharmacodynamics.

A–D: HCV Viral Kinetics (A and C) and pharmacokinetics (B and D) in HIV/HCV genotype 1 co-infected patients treated with peg-interferon alfa-2b (1.5 µg/kg/wk) and ribavirin (1–1.2 g/d). Median HCV RNA concentrations are plotted (A) as function of race (black circles for African Americans and red squares for Caucasians), and (C) according to the treatment outcome (green circles for SVR, blue triangles for REL, red squares for VB and black diamonds for NR) for the first 84 days of treatment. Note the different time scale in x-axis at days 0–7 versus days 7–84, in order to clarify the transient viral rebound at day 3–7. Interferon-alpha serum concentrations are plotted (B) as function of race (black circles for African Americans and red squares Caucasians), and (D) according to the treatment outcome (green circles for SVR, blue triangles for REL, red squares for VB and black diamonds for NR) for the first 14 days of treatment. Statistical significant differences in viral decline between the groups are marked with * (P<0.05) or ** (P<0.03). Dashed horizontal lines mark the level of HCV RNA and peg-IFN detection.
E–H: Correlation between early viral kinetic parameters and therapeutic response in African-American (A and C) and Caucasian (B and D) HIV/HCV co-infected patients. Sustained viral response (SVR, green circles) can be predicted in our study with NPV=100% and PPV=100% by the combination of HCV-RNA decline larger than 1.0 log IU/ml at day 3 (x-axis in A and B) and HCV-RNA load below 5.0 log IU/ml at day 28 (y-axis in A and B). Non-responders (NR, black diamonds) have lower decline in viral load than patients with viral breakthrough (VB, red squares) and patients with relapse (REL, blue triangles). Also, a second phase viral decline slope (y-axis in C and D) slower than 0.3 log/week is predictive of lack of SVR, but the transient rebound at days 3–7 (x-axis in C and D) is not correlated with therapeutic response). In addition, it is possible to observe the faster decline in Caucasians (B and D) as compared to African-Americans (A and C), in both first phase decline at day 3 and second phase decline, as well as viral load at day 28.

L Rozenberg, et al. AIDS. ;23(18):2439-2450.

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