Multivariable Results from Cox Proportional Hazards Regression Analyses of Predictors of Virologic Rebound.

<p>Abbreviations: HR, hazard ratio; CI, confidence interval; T0, time of first viral load result using the ultrasensitive Taqman assay (study entry); NNRTI, non-nucleoside reverse transcriptase inhibitor; ART, antiretroviral therapy.</p>a<p>N = 773 (5 cases with missing demographic or laboratory values).</p>b<p>Significant association, P<0.05.</p>c<p>N = 540, including 180 subjects with VL <48 copies, and 360 subjects with undetectable VL propensity score-matched to the <48 group. Only effects of the T0 VL group were compared as propensity score-matching adjusted for baseline differences between cohorts.</p

Baseline (T0) Study Population Characteristics.

<p>Abbreviations: T0, time of first viral load result using the ultrasensitive Taqman assay (study entry); TND, target not detected; NNRTI, non-nucleoside reverse transcriptase inhibitor.</p>a<p>4 missing values, N = 774.</p>b<p>Number and percent within T0 viral load group.</p>c<p>Includes protease inhibitor, integrase inhibitor-based and other regimens.</p>d<p>Includes 180 subjects with VL <48 copies, and 360 subjects with undetectable VL propensity score-matched to the <48 group.</p>e<p>Mean CD4 counts were identical after propensity matching.</p

Average estimated glomerular filtration rate in patients during and after telaprevir therapy, by baseline kidney function.

<p>3a. Baseline eGFR ≥ 90 mL/min/1.73m² 3b. Baseline eGFR < 90 mL/min/1.73m². Mean eGFR (solid gray circle) and one-standard deviation error bars are shown with shading at baseline, on treatment (nadir), 12 weeks after finishing telaprevir, while still on PegIFN and RBV, and then one year after completing telaprevir, off all treatment. P < 0.01 for changes between baseline eGFR and eGFR while on telaprevir in both groups. There is no signficant difference between baseline eGFR and eGFR 12 weeks or one year post telaprevir. Fig 3a shows patients with baseline eGFR ≥ 90mL/min/1.73m². (N = 44). 3b.) Includes patients with baseline eGFR < 90mL/min/1.73m² (N = 34). Values that fell outside of one standard deviation are shown with hollow gray circles. eGFR = estimated glomerular filtration rate.</p

Timeline of Triple Therapy, Short and Long-term Follow-up.

<p>Patients were prescribed triple therapy (telaprevir, Peg-IFN, and ribavirin) for twelve weeks. Based on clinical characteristics and at the providers discretion patients then continue Peg-IFN and ribavirin for a total of 24–48 weeks. Short-term follow-up was obtained 12 weeks after telaprevir was discontinued (at week 24). Long-term follow-up was obtained 12 months after telaprevir was discontinued (at week 62).</p

Univariate and multivariable logistic regression model predicting development of significant creatinine rise during therapy with telaprevir.

<p>^{Abbreviations: HIV = human immunodeficiency virus, eGFR = estimated glomerular filtration rate}</p><p>Univariate and multivariable logistic regression model predicting development of significant creatinine rise during therapy with telaprevir.</p

Peak rise in serum creatinine during telaprevir therapy.

<p>Bar graphs represent the numbers of patients who experienced a maximum rise in serum creatinine in the above ranges. The majority (55%) of patients experienced a small (< 0.2mg/dl) rise in creatinine during telaprevir therapy. However, thirty-one percent developed significant creatinine rise ≥ 0.3mg/dl, shown by a dashed vertical line.</p

Symptoms contributing to the discontinuation of telaprevir (n = 25).

<p>^{Twenty-five patients discontinued telaprevir therapy. Numbers may add up to more than total N if combinations of multiple symptoms led to discontinuation.}</p><p>^{<b>ϕ -</b> Significant at the level of P < 0.05}</p><p>^{*Other reasons for discontinuation that each affected one patient included fever and noncomplicance.}</p><p>Symptoms contributing to the discontinuation of telaprevir (n = 25).</p

Univariate and multivariable linear regression model predicting change in eGFR over one year follow-up.

<p>^{Abbreviations: HIV = human immunodeficiency virus, eGFR = estimated glomerular filtration rate}</p><p>Univariate and multivariable linear regression model predicting change in eGFR over one year follow-up.</p

Conflicting effects of atazanavir therapy on atherosclerotic risk factors in stable HIV patients: A randomized trial of regimen switch to atazanavir

<div><p>Bilirubin acts as a potent endogenous antioxidant, with higher concentrations associated with lower rates of CVD; the antiretroviral drug atazanavir (ATV) increases bilirubin levels but may also increase von Willebrand factor levels. We tested the hypothesis that increasing endogenous bilirubin using ATV would improve cardiometabolic risk factors and vascular function in older patients with HIV. Ninety participants were enrolled in two study protocols. In protocol 1, we evaluated markers of inflammation, thrombosis, and conduit artery endothelial function in subjects on non-ATV containing regimens. Participants were randomly assigned to continue baseline treatment or switch to an ATV-based regimen. Measurements were made at baseline and 28 days. In the protocol 2, we enrolled 30 subjects who received atazanavir for more than one year and were compared to the aim 1 protocol subjects at baseline. 60 subjects were enrolled in the first protocol (mean age 53, +/- 6 years), with 31 randomized to ATV and 29 continuing baseline treatment. Atazanavir significantly increased serum total bilirubin levels (p<0.001) and acutely but not chronically plasma total antioxidant capacity (p<0.001). An increase in von Willebrand Factor (p<0.001) and reduction in hs-CRP (p = 0.034) were noted. No changes were seen in either flow-mediated endothelium-dependent or vasodilation. In cross-sectional analysis (second protocol), similar findings were seen in the baseline attributes of non-atazanavir-based and long-term atazanavir users. Increasing serum bilirubin levels with atazanavir in subjects with HIV reduces hs-CRP, temporarily reduces oxidative stress, but increases von Willebrand Factor. Atazanavir does not improve endothelial function of conduit arteries.</p><p><b>Trial registration:</b> ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT03019783" target="_blank">NCT03019783</a>.</p></div

Baseline demographics and clinical characteristics of patients treated with telaprevir (n = 78).

<p>^{HIV = Human Immunodeficiency Virus, eGFR = estimated glomerular filtration rate, HCV = hepatitis C virus, SVR = sustained viral response}</p><p>Baseline demographics and clinical characteristics of patients treated with telaprevir (n = 78).</p