Metabolic impact of raltegravir-based salvage salvage regimens over 96 weeks.

<p>In both figures values are presented as mean±standard deviation (SD). The dimension of the cohort at each timepoint is reported below (n.). (2A) AST and ALT slope over 96 weeks, all data caught (even 1 acute hepatitis B), (2B) total and fractionated cholesterol slope.</p

Adverse events (n) reported during the observation, classified by CTCAE grade.

§<p>Acute hepatitis HBV,</p>*<p>Plus one case of: renal cancer, grade 3 rhabdomyolysis, non-Hodgkin’s lymphoma, coronary heart disease, diabetes, Basedow’s disease, portal hypertension, arterial hypertension, urinary tract infection, fever, acute psychosis, dizziness, flushing, macular rash of skin and glans, gout, cataract, dry skin, asymptomatic hyperuricemia and LDH increase.</p

Main demographic features of the SALIR cohort (n = 320).

<p>SD  =  Standard Deviation, IDU  =  intravenous drug user, MSM =  male having sex with males, IQR  =  interquartile range, ARV  =  antiretroviral, ART =  antiretroviral therapy, HDL  =  high density lipoprotein, AST  =  aspartate aminotransferase, ALT  =  alanine aminotransferase.</p

Predictors of raltegravir effectiveness.

<p>ITT  =  intention-to-treat analysis, OT  =  on-treatment analysis, IDU  =  intravenous drug user; ARV  =  antiretroviral; ART  =  antiretroviral therapy; HCV  =  Hepatitis C Virus; HBV  =  Hepatitis B Virus.</p>*<p>only including selected variables (P<0.15).</p>§<p>P<0.05.</p

CD4+ T cells/mmc slope over 96 weeks and proportion of subjects achieving and maintaining optimal viral suppression, set for homogeneity at <50 copies/mL.

<p>The dimensions of the population at each timepoint is reported below (n). In <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039222#pone-0039222-g001" target="_blank">figure 1A</a> values are presented as mean±standard deviation (SD). In <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039222#pone-0039222-g001" target="_blank">figure 1B</a> the spotted line presents data in the on treatment analysis, while the continuous line shows the intention-to-treat, missing data  =  failure analysis (ITT; M = F).</p

Population kinetic parameters for the best HCV and ALT kinetic model.

<p>Population kinetic parameters for the best HCV and ALT kinetic model.</p

Decrease of viral load and ALT at different time points under treatment according to NS5A-inhibitors and interferon administration.

<p>These graphs shows the median of predictions of ALT and HCV-RNA in different groups of treatment obtained by simulations from the parameter estimates of the two models. ALT, alanine transaminase; IFN, interferon.</p

Predicted kinetic profiles obtained by simulations from the viral and ALT kinetic models.

<p>(panel <b>A</b>) Different viral kinetics according to HCV-genotypes, NS5A-inhibitors and interferon administration, (panel <b>B</b>) Different ALT kinetics according to NS5A-inhibitors and interferon administration. ALT, alanine transaminase; IFN, interferon.</p

Biphasic kinetics of HCV-RNA decay, and ALT drop during all-DAA and TVR+PR treatment and follow-up.

<p>In <i>upper panels</i>, median values with 95% confidence interval of HCV-RNA (black dots) and ALT (grey squares) during all-DAAs (panel <b>A</b>) and TVR+PR (panel <b>B</b>) treatment are reported. End of follow-up is at 12 weeks after treatment discontinuation. Black dotted line represents the lower limit of detection of HCV-RNA (12–15 IU/ml). Grey dotted line represents normality range of ALT values in females (45 IU/ml). Histograms in <i>lower panels</i> represent the percentages of patients with HCV-RNA below the lower limit of detection (panel <b>C</b>) and with normal ALT values (panel <b>D</b>) during all-DAAs (black) and TVR+PR (grey) treatment. Normal ALT values were considered as <55 IU/ml in men, and <45 IU/ml in women. ALT, alanine transaminase; DAA, direct-acting antivirals; EOT, end of treatment; IU, international units; LLOD, lower limit of detection (<12–15 IU/ml, not detected); PR, pegylated interferon and ribavirin; TVR, telaprevir. * p-value <0.05 by Fisher exact test; ** p-value ≤0.001 by Fisher exact test.</p

Cox analysis for factors influencing ALT normalization during treatment.

<p>Cox analysis for factors influencing ALT normalization during treatment.</p