Sensitivity analysis by background antigen prevalence.

<p>The results of one-way sensitivity analysis varying the background cryptococcal antigen prevalence in patients entering ART programmes with CD4 cell counts <100 cells/µL. The cost of current standard of care (no prevention, or status quo) is shown by the dotted line, and the cost of the CRAG screening with targeted treatment of CRAG positive individuals with high dose fluconazole (no LPs) is shown by the solid line. The screen and treat strategy dominated the standard of care at antigen prevalences of 0.6% and higher. The shaded area represents the range of baseline CRAG prevalence figures reported in patients with CD4 counts <100 cell/µL at ART programme entry. Costs are expressed as mean cost per patient/year in the ART programme.</p

Costs.

*<p>Medication costs were from government tender prices, test costs were from the National Health Laboratory Services, and lumbar puncture costs were based on the Uniform Patient Fee Schedule. The overhead and staff cost per inpatient day at the secondary level and the overhead and staff cost per outpatient department visit was taken from Cleary et al <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069288#pone.0069288-Cleary1" target="_blank">[48]</a>. The overhead components of these costs were inflated using the Consumer Price Index, while clinical staff costs were recalculated using 2010 government salary scales. Costs were expressed in 2010 prices, and were converted to United States Dollars (US$) based on the average exchange rate between 1 January and 31 December 2010 (US$1 = ZAR7.34; <a href="http://www.oanda.com" target="_blank">www.oanda.com</a>).</p

Baseline input assumptions and transition probabilities.

*<p>The incidence of CM varied according to CD4 count strata, and time on ART to account for CD4 cell count increases and the acompanying reduction in risk of developing CM. The time stratification was into 3 month blocks according to time from ART initiation, and the data used to derive these probabilities was from a large South African cohort <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069288#pone.0069288-Jarvis5" target="_blank">[45]</a>.</p

Simplified markov model structure.

<p>Transition probabilities are listed as C1, C2, S1 etc. Variable names, descriptions and values are derived from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069288#pone-0069288-t001" target="_blank">table 1</a>, as follows: <b><i>S1</i></b> - Proportion with subclinical CM at baseline, CD4<50 cells/µL = 0.13, CD4 50–100 cells/µL = 0.03. <b><i>S2</i></b> - Of those with subclinical CM, Proportion with CSF infection = 0.5. <b><i>P1</i></b> - Proportion starting ART with CD4<50 cells/µl = 0.5. <b><i>C1</i></b> - Probability of developing CM, by baseline CD4 category and time on ART: <i>CD4<50 cells/µl = </i>252 per 1000 patient years (pyo) up to 3 months on ART, 72 per 1000 pyo 4–6 months on ART, 36 per 1000 pyo 7–9 months on ART, 0 per 1000 pyo 10–12 months. <i>CD4 50–100 cells/µl</i> = 56 per 1000 pyo up to 3 months on ART, 16 per 1000 pyo 4–6 months on ART, 8 per 1000 pyo 7–9 months on ART, 0 per 1000 pyo 10–12 months. <b><i>R1</i></b> - Relative risk of CM with low dose fluconazole prophylaxis = 0.21. <b><i>R2</i></b> - Relative risk of CM for CRAG positive taking high dose fluconazole prophylaxis = 0.1. <b><i>R3</i></b> - Relative risk of CM for CRAG positive with amphotericin for CSF positive patients, fluconazole for CSF negative patients = 0. <b><i>D1</i></b> - Probability of dying of acute CM = 45% dead at 1 month with CM. <b><i>D2</i></b> - Probability of dying of CM within 1 year = 55% dead at 12 months on ART.</p

Cost-effectiveness.

<p>Mean cost = Mean per-patient cost for prevention and/or treatment of CM, US$, during first year of ART.</p><p>Life years = Mean life expectancy one year after ART programme entry.</p><p>ICER = ratio of difference in cost to difference in outcome.</p>*<p>Uncertainty interval.</p>†<p>Higher cost than more effective option(s).</p

Pathway of care for HIV-infected individuals presenting in with CD4 count < 200 cells/mm³ in intervention and standard care arms in Tanzania.

<p>*Under standard care, TB screening is done using smear microscopy examination or chest x-ray. For this study, Xpert screening was used in both arms at baseline.</p

Mean cost (in USD 2012) per patient month for patients initiating ART treatment with CD4 count <200 cells/mm³ in Tanzania for both standard care (control) and the REMSTART trial intervention arms.

<p>Mean cost (in USD 2012) per patient month for patients initiating ART treatment with CD4 count <200 cells/mm³ in Tanzania for both standard care (control) and the REMSTART trial intervention arms.</p

Results of the sensitivity analyses exploring the impact of uncertainty in key variables on the average cost estimates for patients initiating ART treatment with CD4 count <200 cells/mm³ in Dar es Salaam, Tanzania.

<p>Results of the sensitivity analyses exploring the impact of uncertainty in key variables on the average cost estimates for patients initiating ART treatment with CD4 count <200 cells/mm³ in Dar es Salaam, Tanzania.</p

Unit costs (in 2012 US$) of the different components of ART services for patients initiating treatment with CD4 count <200 cells/mm³ in Dar es Salaam, Tanzania.

<p>Unit costs (in 2012 US$) of the different components of ART services for patients initiating treatment with CD4 count <200 cells/mm³ in Dar es Salaam, Tanzania.</p

Characteristics, HIV disease progression and ART treatment regimen of for study participants (HIV patients presenting in the advanced stages of HIV-infection—CD4 <200cells/mm³), in Dar es Salaam, Tanzania.

<p>Characteristics, HIV disease progression and ART treatment regimen of for study participants (HIV patients presenting in the advanced stages of HIV-infection—CD4 <200cells/mm³), in Dar es Salaam, Tanzania.</p