Date of download: 5/28/2016 From: When to Start Antiretroviral Therapy in Resource-Limited Settings Ann Intern Med. 2009;151(3): doi: / Decision tree that outlines ART strategy options over the next 5 years while trial results are pending.The payoffs in terms of both clinical outcomes and costs are delineated to the right of the tree. The probability P represents the chance that the forthcoming trials studying ART initiation will demonstrate a clinical benefit of ART initiation at a CD4 count threshold of × 10 9 cells/L. Using a cost-effectiveness willingness-to-pay threshold of 3 times the per-capita gross domestic product of South Africa ($16 200/year of life saved), the tree suggests that initiating ART at CD4 counts less than × 10 9 cells/L now would be optimal for values of P such that $ ≥ {[P × costs (left branch)] + [(1 − P) × costs (middle branch)] – [costs (right branch)]} ÷ {[P × outcomes (left branch)] + [(1 − P) × outcomes (middle branch)] – [outcomes (right branch)]}. As described in the Results section, values of P greater than 0.17 satisfy this decision rule. ART = antiretroviral therapy. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

Date of download: 5/28/2016 From: When to Start Antiretroviral Therapy in Resource-Limited Settings Ann Intern Med. 2009;151(3): doi: / Model-based projections over the next 5 years for strategies of ART initiation at CD4 count thresholds of × 10 9 cells/L and × 10 9 cells/L.Squares indicate total deaths and circles indicate total opportunistic diseases for the 2 strategies (left vertical axis). The bars indicate excess total costs of initiating ART at a threshold of × 10 9 cells/L compared with × 10 9 cells/L over a 5-year horizon (right vertical axis). The horizontal axis represents results at varying proportions of HIV cases identified and linked to care in the population. ART = antiretroviral therapy. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

Date of download: 5/28/2016 From: When to Start Antiretroviral Therapy in Resource-Limited Settings Ann Intern Med. 2009;151(3): doi: / Incremental cost-effectiveness of ART at CD4 count thresholds of × 10 9 cells/L versus × 10 9 cells/L at alternative probability values.P represents the probability that the trial will confirm model-based results indicating a benefit of earlier therapy (see Methods and Figure 1). The incremental cost-effectiveness is provided for the 5-year time horizon. The height of the bar provides the cost-effectiveness ratio of an initiation threshold of × 10 9 cells/L versus × 10 9 cells/L for alternative values of P; bars that remain below the horizontal solid line (<3 × GDP) are considered to be cost-effective and those that remain below the horizontal dotted line (<1 × GDP) are considered to be very cost-effective. ART = antiretroviral therapy; GDP = gross domestic product in South Africa (U.S. $5400); YLS = year of life saved. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

Date of download: 5/28/2016 From: When to Start Antiretroviral Therapy in Resource-Limited Settings Ann Intern Med. 2009;151(3): doi: / Sensitivity analysis on the benefit of ART at a CD4 count less than × 10 9 cells/L.Results from the model suggested a 2-fold decrease in the death rate with ART initiation at a CD4 count <0.350 × 10 9 cells/L. The vertical axis shows the threshold P value at which the trial will demonstrate a benefit of ART initiation at <0.350 × 10 9 cells/L and that also meets the cost-effectiveness threshold criterion of <$ (3 times the gross domestic product of South Africa). The solid arrow indicates the 17% threshold discussed in the article; the open arrow indicates the results if the benefit of ART initiation at <0.350 × 10 9 cells/L were half (1.5) of what the model projected. ART = antiretroviral therapy. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

Date of download: 5/28/2016 From: When to Start Antiretroviral Therapy in Resource-Limited Settings Ann Intern Med. 2009;151(3): doi: / Model-generated survival curves for ART.The annual mortality hazard 2 years after entry into care was 0.01 for a threshold of × 10 9 cells/L, 0.05 for × 10 9 cells/L, and 0.06 for no ART. Two years after entry into care, the composite annual hazard of severe opportunistic disease, tuberculosis, or death was 0.06 for a threshold of × 10 9 cells/L, 0.16 for × 10 9 cells/L, and 0.17 for no ART (data not shown). ART = antiretroviral therapy. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians