Cumulative incident of toxicity and treatment failure in the first treatment

<p><b>Copyright information:</b></p><p>Taken from "Impact of drug classes and treatment availability on the rate of antiretroviral treatment change in the TREAT Asia HIV Observational Database (TAHOD)"</p><p>http://www.aidsrestherapy.com/content/4/1/18</p><p>AIDS Research and Therapy 2007;4():18-18.</p><p>Published online 17 Sep 2007</p><p>PMCID:PMC2048495.</p><p></p> x axis is "years". Y axis is "cumulative incidence". green line represents toxicity failure. red line represents treatment failure [see Figure 2

Immune reconstitution inflammatory syndrome in association with HIV/AIDS and tuberculosis: Views over hidden possibilities-0

<p><b>Copyright information:</b></p><p>Taken from "Immune reconstitution inflammatory syndrome in association with HIV/AIDS and tuberculosis: Views over hidden possibilities"</p><p>http://www.aidsrestherapy.com/content/4/1/29</p><p>AIDS Research and Therapy 2007;4():29-29.</p><p>Published online 30 Nov 2007</p><p>PMCID:PMC2216023.</p><p></p>ion. Initiation of HAART in the subject leads to abrupt restoration of CD4+ T-cells and almost any pathogen-specific immune response. IRIS developers have a high burden of LPS and proinflammatory cytokines produced against LPS could result in an exaggerated, nonspecific attack on latent mycobacterial antigens that are presented in the local lymph nodes leading to localized inflammation. We also hypothesize that subjects that do not develop IRIS could have developed either tolerance (anergy) to persistent LPS and tubercle antigens or could have normal FOXP3+ gene (not shown) and that those with defective FOXP3+ gene or enormous plasma LPS could be vulnerable to IRIS (as demonstrated by researchers that defective FOXP3+ gene is associated with increased risk for inflammatory conditions). (Bold lines indicate the availability of clinical/experimental evidence and dashed lines indicate the possible mechanism)

Incremental cost-effectiveness of additional strategies for TB preventive therapy.

<p><b>TB</b>: Tuberculosis; <b>USD</b>: US Dollars; <b>YLS</b>: Years of life saved: <b>IPT</b>: Isoniazid-based preventive therapy; <b>6H</b>: Six-month regimen of isoniazid; <b>3RH</b>: Three-month regimen of isoniazid plus rifampin; <b>6EH</b>: Six-month regimen of isoniazid plus ethambutol; <b>36H</b>: Three-year regimen of isoniazid; <b>3RPTH</b>: Three-month regimen of isoniazid plus rifapentine.</p>*<p>The incremental cost-effectiveness ratios may not exactly match the ratios of lifetime cost and life expectancy reported in the table due to rounding.</p>a<p>Weakly dominated (more expensive but confers less clinical benefit than some combination of other strategies) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036001#pone.0036001-Gold1" target="_blank">[12]</a>.</p>b<p>Strongly dominated (more expensive but confers less clinical benefit than some other strategy) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036001#pone.0036001-Gold1" target="_blank">[12]</a>.</p

Multi-way sensitivity analysis of 6EH major toxicity, regimen completion, and efficacy

<p>. Major toxicity associated with 6EH, percent cohort completion of the regimen, and efficacy of the regimen are varied simultaneously. The solid line represents the point estimate of efficacy for the 6EH regimen as observed in the trial, i.e. a rate ratio of tuberculosis incidence of 0.35 compared to no IPT, varied over a range of percent cohort completion of the regimen and probability of major toxicity. The shaded area to the right of the line represents all values at which the 6EH regimen is cost-effective, based on 3x the GDP <i>per capita</i> of India. The hatched line represents the leftwards shift in the boundary of cost-effectiveness when the rate ratio of TB incidence with 6EH is 0.21 compared to no IPT, as calculated from the lower bound of the 95% confidence interval of the trial. The dotted line represents the rightwards shift in the boundary of cost-effectiveness when the relative risk of TB with 6EH is 0.50 compared to no IPT, as calculated from the upper bound of the 95% confidence interval of the trial. The diamond in the lower right corner represents the base case, trial-based scenario, where percent cohort completion is 100% and the probability of major toxicity is 0.0029. <b>6EH:</b> Six-month regimen of isoniazid plus ethambutol, <b>IPT</b>: Isoniazid-based Preventive Therapy, <b>GDP</b>: Gross Domestic Product.</p

Model validation and 10-year outcomes for TB incidence and cost of 6EH and 36H compared to no IPT.

<p><b>TB</b>: Tuberculosis; <b>PY</b>: Person-Years; <b>USD</b>: US Dollars; <b>IPT</b>: Isoniazid-based TB preventive therapy; <b>6EH</b>: Six-month regimen of isoniazid plus ethambutol; <b>36H</b>: Three-year regimen of isoniazid.</p

Tornado diagram of one-way sensitivity analyses comparing the 36H regimen to the 6EH regimen

<p>. Selected model parameters are listed on the vertical axis, with the range examined in sensitivity analyses listed in parentheses. The horizontal axis demonstrates the impact of changes in the parameter values on the incremental cost-effectiveness ratios for the 36H regimen compared to 6EH regimen. The solid vertical line indicates the incremental cost-effectiveness ratio estimate ($3,120/YLS) of the base case, and the dashed vertical line indicates the suggested cost-effectiveness threshold ratio of$2,940/YLS (3x GDP India). Values in white in the center of the bars indicate the threshold value of each parameter at which the cost-effectiveness ratio for 36H compared to 6EH is equal to $2,940/YLS. For example, a total cost of$90 for the 36H regimen was assumed in the base case. The incremental cost-effectiveness ratio of 36H compared to 6EH was less than or equal to $2,940/YLS (i.e. cost-effective by international standards) when the cost of 36H was less than$70. <b>36H:</b> Thirty-six-month regime of isoniazid, <b>6EH</b>: Six-month regimen of isoniazid plus ethambutol, <b>YLS</b>: Year of Life Saved, <b>GDP</b>: Gross Domestic Product.</p

Baseline cohort characteristics, TB and HIV natural history, HIV treatment parameters.

<p><b>SD</b>: Standard deviation; <b>IQR</b>: Interquartile range; <b>TB</b>: Tuberculosis<b>; PY</b>: Person-Years; <b>MDR</b>: Multidrug-resistant; <b>ART</b>: Antiretroviral therapy.</p>a<p>Probability of death within 6 months after active TB.</p

Virologic response at Week 96, by randomised arm, study population and screening strata.

<p>RAL = lopinavir/ritonavir+raltegravir Control = lopinavir/ritonavir+2/3 nucleoside/nucleotide reverse transcriptase inhibitors. *grey circle = screening plasma viral load strata, P interaction = 0.81, bars are 95%confidence intervals (CI).</p

Mean change from baseline in CD4+ T cells/mm³ over 96 weeks by randomised arm.

<p>RAL = lopinavir/ritonavir+raltegravir Control = lopinavir/ritonavir+2/3 nucleoside/nucleotide reverse transcriptase inhibitors. (Control- - - RAL ---, bars indicate standard deviation).</p

Absolute mean cholesterol fractions and ratio over 96 weeks by randomised arm.

<p>(A) total cholesterol, (B) high density lipoprotein (HDL) cholesterol, (C) low density lipoprotein (LDL) cholesterol, (D) Total:HDL cholesterol ratio. RAL = lopinavir/ritonavir+raltegravir Control = lopinavir/ritonavir+2/3 nucleoside/nucleotide reverse transcriptase inhibitors. (Control - - - RAL ---, bars indicate standard deviation).</p