Centers for Disease Control and Prevention
Cost-Effectiveness of Community-Based TB/HIV Screening and Linkage to Care in Rural South AfricaSUPPLEMENTARY APPENDIXJennifer A. Gilbert1,2*, Sheela V. Shenoi3, Anthony P. Moll3,4, Gerald H. Friedland1,3, A. David Paltiel5, and Alison P. Galvani1,21 Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA2 Center for Infectious Disease Modeling and Analysis, Yale School of Public Health, New Haven, CT, USA 3 Department of Medicine, Section of Infectious Diseases, AIDS Program, Yale University School of Medicine, New Haven, CT, USA4 Church of Scotland Hospital, Tugela Ferry, KwaZulu-Natal, South Africa 5 Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA E-mail: jennifer.gilbert@aya.yale.edu (JAG)Additional MethodsMathematical modelTo examine the potential impact of community-based TB/HIV screening and linkage to care over a 10-year period, we extended our previous model of TB and HIV transmission in a rural area of South Africa ADDIN EN.CITE <EndNote><Cite><Author>Gilbert</Author><Year>2015</Year><RecNum>93</RecNum><DisplayText><style face="superscript">1</style></DisplayText><record><rec-number>93</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1429651825">93</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, J A</author><author>Long, E F</author><author>Brooks, R P</author><author>Friedland, G H</author><author>Moll, A P</author><author>Townsend, J P</author><author>Galvani, A P</author><author>Shenoi, S V</author></authors></contributors><titles><title>Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0126267</pages><volume>10</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>1 to include healthcare costs and years of life saved. We additionally updated the model parameters to reflect the most current data for TB and HIV incidence and treatment coverage. ADDIN EN.CITE <EndNote><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><DisplayText><style face="superscript">2,3</style></DisplayText><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite><Cite><Author>Statistics South Africa</Author><Year>2014</Year><RecNum>171</RecNum><record><rec-number>171</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1438704334">171</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>Statistics South Africa,</author></authors></contributors><titles><title>Mid-year population estimates 2014</title></titles><dates><year>2014</year></dates><pub-location>Pretoria, South Africa</pub-location><urls></urls></record></Cite></EndNote>2,3 We modeled drug-sensitive TB, MDR-TB, and XDR-TB, including acquired and amplified drug resistance, self-cure, strain fitness, exogenous re-infection, and mortality,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 4 and parameterized our model using data from clinical and epidemiological studies (Tables I and II). In line with other models of TB infection,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EeWU8L0F1dGhvcj48WWVhcj4yMDAwPC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 6,7 and consistent with clinical studies, a small percentage of smear-negative patients are categorized as infectious. ADDIN EN.CITE <EndNote><Cite><Author>Hernandez-Garduno</Author><Year>2004</Year><RecNum>40</RecNum><DisplayText><style face="superscript">8</style></DisplayText><record><rec-number>40</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">40</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hernandez-Garduno, E.</author><author>Cook, V.</author><author>Kunimoto, D.</author><author>Elwood, R. K.</author><author>Black, W. A.</author><author>FitzGerald, J. M.</author></authors></contributors><auth-address>Department of Medicine, The University of British Columbia, Vancouver, BC, Canada.</auth-address><titles><title>Transmission of tuberculosis from smear negative patients: a molecular epidemiology study</title><secondary-title>Thorax</secondary-title><alt-title>Thorax</alt-title></titles><periodical><full-title>Thorax</full-title><abbr-1>Thorax</abbr-1></periodical><alt-periodical><full-title>Thorax</full-title><abbr-1>Thorax</abbr-1></alt-periodical><pages>286-90</pages><volume>59</volume><number>4</number><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>British Columbia/epidemiology</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Cluster Analysis</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Tuberculosis/epidemiology/*transmission</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0040-6376 (Print)
0040-6376 (Linking)</isbn><accession-num>15047946</accession-num><urls><related-urls><url> The effectiveness of TB treatment is determined by drug efficacy, adherence, and default. ADDIN EN.CITE <EndNote><Cite><Author>WHO</Author><Year>2013</Year><RecNum>10</RecNum><DisplayText><style face="superscript">9</style></DisplayText><record><rec-number>10</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753037">10</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>Global Tuberculosis Report 2013</title></titles><dates><year>2013</year></dates><pub-location>Geneva, Switzerland</pub-location><urls></urls></record></Cite></EndNote>9 Individuals who receive effective treatment recover from active disease, while individuals who are ineffectively treated remain infectious and are at risk for acquired or amplified resistance.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NdWtoZXJqZWU8L0F1dGhvcj48WWVhcj4yMDA0PC9ZZWFy
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ADDIN EN.CITE.DATA 10 A small proportion of patients with active TB or ineffective treatment may also self-cure and return to a latently infected state. ADDIN EN.CITE <EndNote><Cite><Author>Dye</Author><Year>1998</Year><RecNum>34</RecNum><DisplayText><style face="superscript">11</style></DisplayText><record><rec-number>34</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">34</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dye, C.</author><author>Garnett, G. P.</author><author>Sleeman, K.</author><author>Williams, B. G.</author></authors></contributors><auth-address>Global Tuberculosis Programme, WHO, Geneva, Switzerland. dyec@who.ch</auth-address><titles><title>Prospects for worldwide tuberculosis control under the WHO DOTS strategy. Directly observed short-course therapy</title><secondary-title>Lancet</secondary-title><alt-title>Lancet</alt-title></titles><periodical><full-title>Lancet</full-title><abbr-1>Lancet</abbr-1></periodical><alt-periodical><full-title>Lancet</full-title><abbr-1>Lancet</abbr-1></alt-periodical><pages>1886-91</pages><volume>352</volume><number>9144</number><edition>1998/12/24</edition><keywords><keyword>*Communicable Disease Control</keyword><keyword>Developing Countries</keyword><keyword>Europe/epidemiology</keyword><keyword>HIV Infections/epidemiology</keyword><keyword>Health Priorities</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Models, Theoretical</keyword><keyword>Netherlands/epidemiology</keyword><keyword>Sensitivity and Specificity</keyword><keyword>Tuberculosis/epidemiology/*prevention & control</keyword><keyword>World Health Organization</keyword></keywords><dates><year>1998</year><pub-dates><date>Dec 12</date></pub-dates></dates><isbn>0140-6736 (Print)
0140-6736 (Linking)</isbn><accession-num>9863786</accession-num><urls><related-urls><url> Patients who successfully complete treatment and recover may relapse to active disease. ADDIN EN.CITE <EndNote><Cite><Author>Dye</Author><Year>1998</Year><RecNum>34</RecNum><DisplayText><style face="superscript">11</style></DisplayText><record><rec-number>34</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">34</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dye, C.</author><author>Garnett, G. P.</author><author>Sleeman, K.</author><author>Williams, B. G.</author></authors></contributors><auth-address>Global Tuberculosis Programme, WHO, Geneva, Switzerland. dyec@who.ch</auth-address><titles><title>Prospects for worldwide tuberculosis control under the WHO DOTS strategy. Directly observed short-course therapy</title><secondary-title>Lancet</secondary-title><alt-title>Lancet</alt-title></titles><periodical><full-title>Lancet</full-title><abbr-1>Lancet</abbr-1></periodical><alt-periodical><full-title>Lancet</full-title><abbr-1>Lancet</abbr-1></alt-periodical><pages>1886-91</pages><volume>352</volume><number>9144</number><edition>1998/12/24</edition><keywords><keyword>*Communicable Disease Control</keyword><keyword>Developing Countries</keyword><keyword>Europe/epidemiology</keyword><keyword>HIV Infections/epidemiology</keyword><keyword>Health Priorities</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Models, Theoretical</keyword><keyword>Netherlands/epidemiology</keyword><keyword>Sensitivity and Specificity</keyword><keyword>Tuberculosis/epidemiology/*prevention & control</keyword><keyword>World Health Organization</keyword></keywords><dates><year>1998</year><pub-dates><date>Dec 12</date></pub-dates></dates><isbn>0140-6736 (Print)
0140-6736 (Linking)</isbn><accession-num>9863786</accession-num><urls><related-urls><url> Both recovered and latently infected individuals can be exogenously re-infected with drug-sensitive or resistant TB, contingent upon partial immunity and the time-dependent risk of infection. ADDIN EN.CITE <EndNote><Cite><Author>Cohen</Author><Year>2007</Year><RecNum>42</RecNum><DisplayText><style face="superscript">12</style></DisplayText><record><rec-number>42</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">42</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cohen, T.</author><author>Colijn, C.</author><author>Finklea, B.</author><author>Murray, M.</author></authors></contributors><auth-address>Division of Social Medicine and Health Inequalities, Brigham and Women's Hospital, One Brigham Circle, Boston, MA 02120, USA tcohen@hsph.harvard.edu</auth-address><titles><title>Exogenous re-infection and the dynamics of tuberculosis epidemics: local effects in a network model of transmission</title><secondary-title>J R Soc Interface</secondary-title><alt-title>Journal of the Royal Society, Interface / the Royal Society</alt-title></titles><periodical><full-title>J R Soc Interface</full-title><abbr-1>Journal of the Royal Society, Interface / the Royal Society</abbr-1></periodical><alt-periodical><full-title>J R Soc Interface</full-title><abbr-1>Journal of the Royal Society, Interface / the Royal Society</abbr-1></alt-periodical><pages>523-31</pages><volume>4</volume><number>14</number><keywords><keyword>Cluster Analysis</keyword><keyword>*Disease Outbreaks/prevention & control</keyword><keyword>Europe/epidemiology</keyword><keyword>Humans</keyword><keyword>*Models, Biological</keyword><keyword>Tuberculosis, Pulmonary/*epidemiology/prevention & control/*transmission</keyword></keywords><dates><year>2007</year><pub-dates><date>Jun 22</date></pub-dates></dates><isbn>1742-5689 (Print)
1742-5662 (Linking)</isbn><accession-num>17251134</accession-num><urls><related-urls><url> We modeled the early and late stages of HIV disease, mortality, and prevalence-dependent behavior change, as well as ART initiation and default. HIV-negative individuals can become infected with HIV at a rate proportional to the prevalence of HIV in the population. ADDIN EN.CITE <EndNote><Cite><Author>Actuarial Society of South Africa</Author><Year>2011</Year><RecNum>36</RecNum><DisplayText><style face="superscript">2,13</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">36</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>Actuarial Society of South Africa,</author></authors></contributors><titles><title>ASSA2008 Model</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite></EndNote>2,13 Consistent with clinical recommendations in 2015, HIV-infected individuals with CD4+ cell count below 500 cells per milliliter are eligible to initiate ART, ADDIN EN.CITE <EndNote><Cite><Author>WHO</Author><Year>2010</Year><RecNum>43</RecNum><DisplayText><style face="superscript">14</style></DisplayText><record><rec-number>43</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">43</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>Antiretroviral therapy for HIV infection in adults and adolescents. Recommendations for a public health approach. 2010 revision.</title></titles><dates><year>2010</year></dates><pub-location>Geneva, Switzerland</pub-location><publisher>World Health Organization</publisher><urls></urls></record></Cite></EndNote>14 but only a proportion of actually begin ART. ADDIN EN.CITE <EndNote><Cite><Author>Actuarial Society of South Africa</Author><Year>2011</Year><RecNum>36</RecNum><DisplayText><style face="superscript">2,13</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">36</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>Actuarial Society of South Africa,</author></authors></contributors><titles><title>ASSA2008 Model</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite></EndNote>2,13 HIV-infected individuals who are co-infected with active TB may also start ART, regardless of CD4+ cell count. ADDIN EN.CITE <EndNote><Cite><Author>WHO</Author><Year>2010</Year><RecNum>43</RecNum><DisplayText><style face="superscript">14</style></DisplayText><record><rec-number>43</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">43</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>Antiretroviral therapy for HIV infection in adults and adolescents. Recommendations for a public health approach. 2010 revision.</title></titles><dates><year>2010</year></dates><pub-location>Geneva, Switzerland</pub-location><publisher>World Health Organization</publisher><urls></urls></record></Cite></EndNote>14We take into account both the effect of HIV and ART on TB disease, as well as TB disease on HIV pathogenesis, such that disease progression and mortality rates depend on whether an individual is co-infected.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXJ0aW48L0F1dGhvcj48WWVhcj4xOTk1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 15 Overall, HIV infection increases the likelihood of progression to primary active disease in those infected with TB, the rate at latent infection reactivates to active disease, and mortality from TB disease. ADDIN EN.CITE <EndNote><Cite><Author>WHO</Author><Year>2008</Year><RecNum>45</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>45</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">45</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>WHO, </author></authors></contributors><titles><title>WHO Three I's Meeting. Intensified Case Finding (ICF), Isoniazid Preventive Therapy (IPT) and TB Infection Control (IC) for people living with HIV</title></titles><dates><year>2008</year><pub-dates><date>2-4 April 2008</date></pub-dates></dates><pub-location>Geneva, Switzerland</pub-location><publisher>World Health Organization</publisher><urls></urls></record></Cite></EndNote>16 Infection with HIV also reduces the efficacy of TB treatment, as well as partial immunity to superinfection or reinfection with another TB strain. ADDIN EN.CITE <EndNote><Cite><Author>WHO</Author><Year>2008</Year><RecNum>45</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>45</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">45</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>WHO, </author></authors></contributors><titles><title>WHO Three I's Meeting. Intensified Case Finding (ICF), Isoniazid Preventive Therapy (IPT) and TB Infection Control (IC) for people living with HIV</title></titles><dates><year>2008</year><pub-dates><date>2-4 April 2008</date></pub-dates></dates><pub-location>Geneva, Switzerland</pub-location><publisher>World Health Organization</publisher><urls></urls></record></Cite></EndNote>16 Similarly, active TB disease decreases CD4+ cell counts, speeds up progression to AIDS, and increases mortality.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Nb2RqYXJyYWQ8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFy
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ADDIN EN.CITE.DATA 18-20Intervention StrategiesWe compared the impact of community-based TB/HIV screening and linkage to care over a 10-year time horizon on the disease incidence, mortality, and healthcare costs arising from drug-sensitive TB, MDR-TB, XDR-TB and HIV. Specifically, we compared a total of eight mutually exclusive strategies (Table 1).Status quo TB and HIV detection and treatmentWe evaluated the effectiveness of community-based TB/HIV screening and linkage to care relative to status quo TB and HIV control currently implemented in rural South Africa. In the baseline scenario, individuals with TB and/or HIV symptoms self-present to a healthcare facility for symptom detection (e.g. cough lasting longer than two weeks, fever, night sweats, and/or weight loss), Xpert MTB/RIF (a newer, fully automated, cartridge-based technology to rapidly diagnose both TB disease and rifampicin resistance), sputum smear, and/or chest x-ray. We assume the status quo TB case detection rate to be 72.5%. ADDIN EN.CITE <EndNote><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><DisplayText><style face="superscript">2</style></DisplayText><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite></EndNote>2 The bacteriologic coverage (i.e. the percentage of suspected TB patients who receive microbiologic testing) for KwaZulu-Natal is estimated to be 80%. ADDIN EN.CITE <EndNote><Cite><Author>Health Systems Trust</Author><Year>2012</Year><RecNum>54</RecNum><DisplayText><style face="superscript">21</style></DisplayText><record><rec-number>54</rec-number><foreign-keys><key app="EN" db-id="rtpevvxts09rrnevrr1v9rz022sr292zdwaw" timestamp="1435932531">54</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>Health Systems Trust,</author></authors></contributors><titles><title>Bacteriologic Coverage Rate (%)</title></titles><number>7 April 2015</number><dates><year>2012</year></dates><pub-location>South Africa</pub-location><urls><related-urls><url> Per South African treatment guidelines, ADDIN EN.CITE <EndNote><Cite><Author>Republic of South Africa</Author><Year>2014</Year><RecNum>21</RecNum><DisplayText><style face="superscript">22</style></DisplayText><record><rec-number>21</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">21</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>Republic of South Africa,</author></authors></contributors><titles><title>National Tuberculosis Management Guidelines</title></titles><dates><year>2014</year></dates><pub-location>South Africa</pub-location><urls></urls></record></Cite></EndNote>22 patients identified as having rifampicin-sensitive active TB disease through Xpert, as well as patients who do not receive microbiologic testing but are suspected of having active TB disease, are enrolled in first-line therapy (the administration of four oral antibiotics for two months and two antibiotics for at least an additional four months). Any TB patients remaining symptomatic and/or smear positive after two to three months of first-line therapy are suspected of TB drug resistance, then assessed by culture and drug susceptibility testing (DST).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 24,25 Patients who have MDR or XDR-TB confirmed are then started on second-line therapy for at least 24 months. Patients who are initially identified through Xpert as having rifampicin-resistant active TB disease are also started on second-line therapy while awaiting confirmation by DST. Current second-line TB treatment guidelines recommend home-based treatment for MDR-TB management whenever possible, where patients are visited by a nurse for the administration of injectable drugs and supervision of oral medications over a 24-month period. ADDIN EN.CITE <EndNote><Cite><Author>Republic of South Africa</Author><Year>2011</Year><RecNum>18</RecNum><DisplayText><style face="superscript">26</style></DisplayText><record><rec-number>18</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">18</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>Republic of South Africa,</author></authors></contributors><titles><title>Multi-Drug Resistant Tuberculosis. A Policy Framework on Decentralised and Deinstitutionalised Management for South Africa</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>26 XDR-TB patients are hospitalized for at least the intensive phase of their treatment.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SZXB1YmxpYyBvZiBTb3V0aCBBZnJpY2E8L0F1dGhvcj48
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ADDIN EN.CITE.DATA 23,26Following HIV diagnosis, individuals are referred to an HIV clinic to receive a CD4+ cell count to determine their eligibility for ART, but it is estimated that 15% to 45% of patients do not follow-up for this evaluation.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SZXB1YmxpYyBvZiBTb3V0aCBBZnJpY2E8L0F1dGhvcj48
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ADDIN EN.CITE.DATA 27,28 Of those who are determined to be ART-eligible (CD4+ cell count ≤ 500), only around half start treatment,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXNzZXR0PC9BdXRob3I+PFllYXI+MjAxMDwvWWVhcj48
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ADDIN EN.CITE.DATA 31-33 While the current South African guidelines recommend ART for individuals with a CD4+ cell count below 500 cells per milliliter, we additionally considered the scenario where all HIV-infected individuals were eligible for ART, regardless of CD4+ cell count, as has recently been demonstrated to be effective at reducing overall HIV incidence in a population. ADDIN EN.CITE <EndNote><Cite><Author>Group</Author><Year>2015</Year><RecNum>169</RecNum><DisplayText><style face="superscript">32,33</style></DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1438301724">169</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Insight Start Study Group</author></authors></contributors><titles><title>Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection</title><secondary-title>N Engl J Med</secondary-title></titles><periodical><full-title>N Engl J Med</full-title></periodical><dates><year>2015</year><pub-dates><date>Jul 20</date></pub-dates></dates><isbn>1533-4406 (Electronic)
0028-4793 (Linking)</isbn><accession-num>26192873</accession-num><urls><related-urls><url> app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1438301805">170</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Temprano Anrs Study Group</author></authors></contributors><titles><title>A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa</title><secondary-title>N Engl J Med</secondary-title></titles><periodical><full-title>N Engl J Med</full-title></periodical><dates><year>2015</year><pub-dates><date>Jul 20</date></pub-dates></dates><isbn>1533-4406 (Electronic)
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ADDIN EN.CITE.DATA 37,38 We additionally considered the scenario where IPT was given to HIV-positive individuals for the entire duration of their lives, as has been recently recommended by the WHO. ADDIN EN.CITE <EndNote><Cite><Author>WHO</Author><Year>2015</Year><RecNum>172</RecNum><DisplayText><style face="superscript">39</style></DisplayText><record><rec-number>172</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1439047616">172</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>Recommendation on 36 months of isoniazid preventive therapy to adults and adolescents living with HIV in resource-constrained and high TB- and HIV-prevalence settings: 2015 update</title></titles><dates><year>2015</year></dates><publisher>WHO</publisher><urls></urls></record></Cite></EndNote>39 We assumed individuals treated with IPT and adherent to treatment were protected from infection with or latent reactivation of drug-susceptible TB for the duration of the IPT, dependent on treatment efficacy (22–100%) and patient adherence (21–87%), and that IPT does not prevent the reactivation or transmission of drug resistant TB.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XSE88L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 6,35,40 For the status quo scenario, we additionally assumed that only patients who initiated ART received IPT, as is currently implemented in South Africa, ADDIN EN.CITE <EndNote><Cite><Author>Churchyard</Author><Year>2014</Year><RecNum>14</RecNum><DisplayText><style face="superscript">38</style></DisplayText><record><rec-number>14</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">14</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Churchyard, G. J.</author><author>Mametja, L. D.</author><author>Mvusi, L.</author><author>Ndjeka, N.</author><author>Hesseling, A. C.</author><author>Reid, A.</author><author>Babatunde, S.</author><author>Pillay, Y.</author></authors></contributors><titles><title>Tuberculosis control in South Africa: Successes, challenges and recommendations</title><secondary-title>S Afr Med J</secondary-title></titles><periodical><full-title>S Afr Med J</full-title></periodical><pages>244-248</pages><volume>104</volume><number>3 (Suppl 1)</number><dates><year>2014</year></dates><urls></urls></record></Cite></EndNote>38 and that all patients on ART receive IPT. Upon IPT completion, individuals return to baseline relative risk of slower TB reactivation and infection. ADDIN EN.CITE <EndNote><Cite><Author>Houben</Author><Year>2014</Year><RecNum>71</RecNum><DisplayText><style face="superscript">34</style></DisplayText><record><rec-number>71</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">71</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Houben, R. M.</author><author>Sumner, T.</author><author>Grant, A. D.</author><author>White, R. G.</author></authors></contributors><auth-address>TB Modelling Group, Department of Infectious Disease Epidemiology, TB Centre, and Department of Clinical Research, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.</auth-address><titles><title>Ability of preventive therapy to cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-burden settings</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>5325-30</pages><volume>111</volume><number>14</number><dates><year>2014</year><pub-dates><date>Apr 8</date></pub-dates></dates><isbn>1091-6490 (Electronic)
0027-8424 (Linking)</isbn><accession-num>24706842</accession-num><urls><related-urls><url> TB/HIV screening and linkage to careWe model a community-based TB/HIV screening and linkage to care program that combines HIV testing and counseling with TB testing. ADDIN EN.CITE <EndNote><Cite><Author>Gilbert</Author><Year>2015</Year><RecNum>93</RecNum><DisplayText><style face="superscript">1</style></DisplayText><record><rec-number>93</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1429651825">93</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, J A</author><author>Long, E F</author><author>Brooks, R P</author><author>Friedland, G H</author><author>Moll, A P</author><author>Townsend, J P</author><author>Galvani, A P</author><author>Shenoi, S V</author></authors></contributors><titles><title>Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0126267</pages><volume>10</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>1 TB/HIV screening is offered and administered to any individuals within the community who accept TB or HIV testing, with acceptance rates between 70% and 100%.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TbWl0aDwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 41,42 As the first step in this community-based intervention, a questionnaire is used to screen individuals for TB symptoms (sensitivity of 69–79%).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BeWxlczwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJl
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BeWxlczwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 45,46 Currently Xpert technology can only detect rifampicin resistance, and thus XDR-TB diagnoses can only be made after waiting two months for the DST results. We additionally considered the scenario where Xpert could detect resistance to second-line drugs and therefore be used to rapidly diagnose XDR-TB. Individuals are also given a rapid HIV antibody test (sensitivity of 98.2–100%). ADDIN EN.CITE <EndNote><Cite><Author>Branson</Author><Year>2003</Year><RecNum>53</RecNum><DisplayText><style face="superscript">47</style></DisplayText><record><rec-number>53</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">53</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Branson, D.M.</author></authors></contributors><titles><title>Point-of-Care Rapid Tests for HIV Antibodies</title><secondary-title>J Lab Med</secondary-title></titles><periodical><full-title>J Lab Med</full-title></periodical><pages>288-295</pages><volume>27</volume><dates><year>2003</year></dates><urls></urls></record></Cite></EndNote>47 Those who test positive have their result confirmed by a second rapid HIV test, and then have a point-of-care CD4+ cell count performed to immediately determine their ART eligibility status. If eligible, patients are linked to their local ART clinic for ARV treatment and IPT initiation, with approximately 31% of individuals identified as eligible initiating ART and IPT.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TbWl0aDwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 41,42 We assume individuals with a CD4+ cell count less than 500 cells per milliliter to be eligible for ART, as has been recommended by South African ART guidelines. ADDIN EN.CITE <EndNote><Cite><Author>Republic of South Africa Department of Health</Author><Year>2014</Year><RecNum>80</RecNum><DisplayText><style face="superscript">48</style></DisplayText><record><rec-number>80</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1425346203">80</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>Republic of South Africa Department of Health,</author></authors></contributors><titles><title>National consolidated guidelines for the prevention of mother-to-child transmission of HIV (PMTCT) and the management of HIV in children, adolescents and adults</title></titles><dates><year>2014</year><pub-dates><date>December 2014</date></pub-dates></dates><pub-location>Pretoria, South Africa</pub-location><publisher>Department of Health, Republic of South Africa</publisher><urls></urls></record></Cite></EndNote>48 We additionally considered the scenario where all HIV-infected individuals were eligible for ART, irrespective of CD4+ cell count. ADDIN EN.CITE <EndNote><Cite><Author>Group</Author><Year>2015</Year><RecNum>169</RecNum><DisplayText><style face="superscript">32,33</style></DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1438301724">169</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Insight Start Study Group</author></authors></contributors><titles><title>Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection</title><secondary-title>N Engl J Med</secondary-title></titles><periodical><full-title>N Engl J Med</full-title></periodical><dates><year>2015</year><pub-dates><date>Jul 20</date></pub-dates></dates><isbn>1533-4406 (Electronic)
0028-4793 (Linking)</isbn><accession-num>26192873</accession-num><urls><related-urls><url> app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1438301805">170</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Temprano Anrs Study Group</author></authors></contributors><titles><title>A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa</title><secondary-title>N Engl J Med</secondary-title></titles><periodical><full-title>N Engl J Med</full-title></periodical><dates><year>2015</year><pub-dates><date>Jul 20</date></pub-dates></dates><isbn>1533-4406 (Electronic)
0028-4793 (Linking)</isbn><accession-num>26193126</accession-num><urls><related-urls><url> Individuals not yet eligible for ART (with a CD4+ cell count greater than 500 cells per milliliter) are linked to their local ART clinic for IPT, as well as regular CD4+ cell count monitoring.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TbWl0aDwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 41,42 We considered two different approaches to IPT administration: a) 36/12 months of IPT, reflecting current South African guidelines for IPT administration; and b) lifetime IPT for all HIV patients, reflecting recent changes to WHO recommendations and findings that lifetime IPT may greatly reduce TB burden.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XSE88L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 39,49The WHO states that there is not sufficient evidence to conclude that IPT administration increases MDR-TB incidence via the generation of isoniazid mono-resistance, ADDIN EN.CITE <EndNote><Cite><Author>WHO</Author><Year>2015</Year><RecNum>172</RecNum><DisplayText><style face="superscript">39</style></DisplayText><record><rec-number>172</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1439047616">172</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>Recommendation on 36 months of isoniazid preventive therapy to adults and adolescents living with HIV in resource-constrained and high TB- and HIV-prevalence settings: 2015 update</title></titles><dates><year>2015</year></dates><publisher>WHO</publisher><urls></urls></record></Cite></EndNote>39 so we assume that neither status quo IPT nor an increase in IPT coverage via the TB/HIV screening intervention will increase the incidence of MDR-TB. However, some predictions have been made that isoniazid mono-resistance may become highly prevalent after 50 or more years of IPT, thus increasing the burden of MDR and/or XDR-TB.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Db2hlbjwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 6,50 Although the time horizon for our analysis is only 10 years, in a sensitivity analysis we also consider the “worst case” scenario whereby the community-based TB/HIV screening immediately causes 100% of the modeled population to become resistant to isoniazid, thus decreasing the efficacy of first-line TB treatment from 77% to 65% and increasing the probability that first-line treatment failures acquire MDR-TB from 3.8% to 61%.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KYWNvYnNvbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+
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ADDIN EN.CITE.DATA 51 While this worst case scenario is unrealistically pessimistic, and thus is not proposed as a likely possibility, it provides an upper bound on any potential increases in MDR- and XDR-TB incidence and thus on the costs that could arise from expanding IPT coverage.Each modeled TB/HIV screening team consists of a professional nurse, two field health workers, and three counselors who screen between 1,800 and 4,800 individuals annually at community sites, ADDIN EN.CITE <EndNote><Cite><Author>Gilbert</Author><Year>2015</Year><RecNum>93</RecNum><DisplayText><style face="superscript">1</style></DisplayText><record><rec-number>93</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1429651825">93</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, J A</author><author>Long, E F</author><author>Brooks, R P</author><author>Friedland, G H</author><author>Moll, A P</author><author>Townsend, J P</author><author>Galvani, A P</author><author>Shenoi, S V</author></authors></contributors><titles><title>Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0126267</pages><volume>10</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>1 costing between $61.83 and $23.18 per person screened, including the cost of a TB symptom questionnaire and rapid HIV test. We conservatively assume $61.83 per person screened as our base case cost, but vary the screening cost in the sensitivity analysis. In some settings, trained community health workers have been comparably effective at testing and linking individuals to HIV care as counselors, totaling as little as $6 per person screened.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TbWl0aDwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 41 In the sensitivity analysis, we additionally vary the rates of linkage to care to reflect any differences that might arise in other settings. The South African Department of Health aims to screen all individuals for TB once per year, ADDIN EN.CITE <EndNote><Cite><Author>Republic of South Africa</Author><Year>2014</Year><RecNum>21</RecNum><DisplayText><style face="superscript">22</style></DisplayText><record><rec-number>21</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">21</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>Republic of South Africa,</author></authors></contributors><titles><title>National Tuberculosis Management Guidelines</title></titles><dates><year>2014</year></dates><pub-location>South Africa</pub-location><urls></urls></record></Cite></EndNote>22 which we incorporate as the base case, but also consider screening frequencies of once every two years, once every year, and once every six months.Health outcomes and costsWe considered the lifetime costs of TB and HIV detection and treatment among 90,000 adults in a rural South African setting. We performed the analysis over a 10-year time horizon from the perspective of the South African Department of Health, which is typically responsible for all medical costs in rural settings. Health burden was estimated with regard to the number of life years saved by an intervention strategy over the course of the lifetimes of the individuals in the population modeled. Costs and life years were discounted at an annual rate of 3%, following WHO guidelines. ADDIN EN.CITE <EndNote><Cite><Author>WHO</Author><Year>2001</Year><RecNum>101</RecNum><DisplayText><style face="superscript">52</style></DisplayText><record><rec-number>101</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1431361013">101</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>Macroeconomics and health: investing in health for economic development</title><secondary-title>Report of the Commission on Macroeconomics and Health</secondary-title></titles><dates><year>2001</year></dates><pub-location>Geneva</pub-location><urls></urls></record></Cite></EndNote>52 Costs were presented in 2015 US dollars (US$).Cost-effectivenessWe calculated the incremental cost-effectiveness ratio (ICER) of the community-based TB/HIV screening and linkage to treatment strategies detailed above. The ICER of each strategy measures the additional cost per life year saved as the frequency of TB/HIV screening and/or the duration of IPT is increased. In accordance with WHO guidelines, we classified an intervention strategy as “very cost-effective” if its incremental cost-effectiveness ratio (ICER) was less than the South African per capita GDP in 2015 ($6,618) and as “cost-effective” if the ICER was less than three times the per capita GDP ($19,854). ADDIN EN.CITE <EndNote><Cite><Author>WHO</Author><Year>2001</Year><RecNum>101</RecNum><DisplayText><style face="superscript">52,53</style></DisplayText><record><rec-number>101</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1431361013">101</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>Macroeconomics and health: investing in health for economic development</title><secondary-title>Report of the Commission on Macroeconomics and Health</secondary-title></titles><dates><year>2001</year></dates><pub-location>Geneva</pub-location><urls></urls></record></Cite><Cite><Author>World Bank</Author><Year>2013</Year><RecNum>102</RecNum><record><rec-number>102</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1431362413">102</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>World Bank,</author></authors></contributors><titles><title>GDP per capita (current US$)</title></titles><volume>2015</volume><number>11 May 2015</number><dates><year>2013</year></dates><urls><related-urls><url> Strategies with ICERs below the threshold for cost-effectiveness can be considered to be preferred or “economically efficient” strategies. Given that multiple strategies may be classified as cost-effective, the choice regarding which strategy should be implemented will ultimately depend on the Department of Health’s “willingness-to-pay” for each additional year of life saved. A strategy is considered “dominated,” (i.e. not optimal) if it costs more than an alternative strategy that is as or more effective. Uncertainty and Sensitivity AnalysisTo assess the impact of parameter uncertainty on our cost-effectiveness analysis and to estimate the likelihood that a strategy would be optimal at a given willingness-to-pay threshold, we performed a probabilistic sensitivity analysis. ADDIN EN.CITE <EndNote><Cite><Author>Briggs</Author><Year>2012</Year><RecNum>103</RecNum><DisplayText><style face="superscript">54</style></DisplayText><record><rec-number>103</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1432870947">103</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Briggs, A. H.</author><author>Weinstein, M. C.</author><author>Fenwick, E. A.</author><author>Karnon, J.</author><author>Sculpher, M. J.</author><author>Paltiel, A. D.</author><author>Ispor-Smdm Modeling Good Research Practices Task Force</author></authors></contributors><auth-address>Institute of Health & Wellbeing, University of Glasgow, Glasgow, UK. andrew.briggs@glasgow.ac.uk</auth-address><titles><title>Model parameter estimation and uncertainty analysis: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force Working Group-6</title><secondary-title>Med Decis Making</secondary-title></titles><periodical><full-title>Med Decis Making</full-title></periodical><pages>722-32</pages><volume>32</volume><number>5</number><keywords><keyword>Decision Making</keyword><keyword>*Models, Theoretical</keyword><keyword>Stochastic Processes</keyword><keyword>*Uncertainty</keyword></keywords><dates><year>2012</year><pub-dates><date>Sep-Oct</date></pub-dates></dates><isbn>1552-681X (Electronic)
0272-989X (Linking)</isbn><accession-num>22990087</accession-num><urls><related-urls><url> We assigned probability distributions to all parameters and costs by fitting the 95% confidence interval of beta or gamma distributions to plausible ranges from clinical and epidemiological data (ranges are shown in Tables I and II; uncertainty distributions are specified in Table III). Samples were drawn from these parameter distributions 1,000 times using Latin hypercube sampling and run through the model to project distributions of intervention cost and life years saved for each strategy. Net health benefits were calculated from the cost and life years saved distributions as the difference between the average health benefit of an intervention strategy (i.e. life years saved) and the average intervention and healthcare costs, divided by the threshold cost-effectiveness ratio. ADDIN EN.CITE <EndNote><Cite><Author>Stinnett</Author><Year>1998</Year><RecNum>104</RecNum><DisplayText><style face="superscript">55</style></DisplayText><record><rec-number>104</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1432870964">104</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stinnett, A. A.</author><author>Mullahy, J.</author></authors></contributors><auth-address>ICOM Health Economics, Johnson & Johnson, Raritan, New Jersey, USA.</auth-address><titles><title>Net health benefits: a new framework for the analysis of uncertainty in cost-effectiveness analysis</title><secondary-title>Med Decis Making</secondary-title></titles><periodical><full-title>Med Decis Making</full-title></periodical><pages>S68-80</pages><volume>18</volume><number>2 Suppl</number><keywords><keyword>Confidence Intervals</keyword><keyword>Cost-Benefit Analysis/*methods</keyword><keyword>Delivery of Health Care/*economics</keyword><keyword>Humans</keyword><keyword>Quality-Adjusted Life Years</keyword><keyword>Stochastic Processes</keyword></keywords><dates><year>1998</year><pub-dates><date>Apr-Jun</date></pub-dates></dates><isbn>0272-989X (Print)
0272-989X (Linking)</isbn><accession-num>9566468</accession-num><urls><related-urls><url> We calculated the net health benefit of each strategy across a range of willingness-to-pay thresholds. From this, we found the probability that a given scenario had the greatest net health benefit compared to its alternatives at a given level of willingness-to-pay. We used these probabilities to generate cost-effectiveness acceptability curves that quantified the uncertainty surrounding our cost-effectiveness ratio estimates. The acceptability curves demonstrate the likelihood that a given intervention strategy saved the largest number of life years for a given outlay (i.e. was optimal at a given willingness-to-pay threshold). Considering South Africa’s goal of screening all individuals once per year, we also performed a one-way sensitivity analysis to determine the impact of parameters on the cost-effectiveness ratio of annual TB/HIV screening. Specifically, we calculated the ICER of annual TB/HIV screening with 36/12 months of IPT and lifetime IPT at the minimum and maximum value of each parameter (Tables I and II) to determine whether the strategy remained cost-effective at these extreme values.Model EquationsOur model consists of differential equations, characterizing joint TB and HIV transmission in a rural South African community. The modeled disease states and parameters are listed in Tables II and IV. The model diagrams of TB and HIV infection, diagnosis, and treatment are depicted in Figures I-III. For clarity, here we describe TB and HIV transmission separately, where X corresponds to the TB disease state; Y corresponds to the HIV disease state; i = infectious or noninfectious TB; and j = DS (j=1), MDR (j=2), or XDR (j=3) TB; T = TB; H = HIV. However, the model incorporates both TB and HIV disease states simultaneously.Drug Susceptible TBMDR-TBXDR-TBHIVForce of InfectionReferences ADDIN EN.REFLIST 1.Gilbert JA, Long EF, Brooks RP, et al. Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa. PLoS One 2015; 10(5): e0126267.2.WHO. WHO TB Burden Estimates. 2014.3.Statistics South Africa. Mid-year population estimates 2014. Pretoria, South Africa, 2014.4.Basu S, Andrews JR, Poolman EM, et al. Prevention of nosocomial transmission of extensively drug-resistant tuberculosis in rural South African district hospitals: an epidemiological modelling study. Lancet 2007; 370(9597): 1500-7.5.Dye C, Williams BG. Criteria for the control of drug-resistant tuberculosis. Proceedings of the National Academy of Sciences of the United States of America 2000; 97(14): 8180-5.6.Cohen T, Lipsitch M, Walensky RP, Murray M. 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Prevalence of tuberculosis, HIV and respiratory symptoms in two Zambian communities: implications for tuberculosis control in the era of HIV. PLoS One 2009; 4(5): e5602.44.Getahun H, Kittikraisak W, Heilig CM, et al. Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies. PLoS medicine 2011; 8(1): e1000391.45.Dowdy DW, O'Brien MA, Bishai D. Cost-effectiveness of novel diagnostic tools for the diagnosis of tuberculosis. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 2008; 12(9): 1021-9.46.Loveday M, Wallengren K, Voce A, et al. Comparing early treatment outcomes of MDR-TB in decentralised and centralised settings in KwaZulu-Natal, South Africa. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 2012; 16(2): 209-15.47.Branson DM. Point-of-Care Rapid Tests for HIV Antibodies. J Lab Med 2003; 27: 288-95.48.Republic of South Africa Department of Health. National consolidated guidelines for the prevention of mother-to-child transmission of HIV (PMTCT) and the management of HIV in children, adolescents and adults. Pretoria, South Africa: Department of Health, Republic of South Africa, 2014.49.Lawn SD, Wood R, De Cock KM, Kranzer K, Lewis JJ, Churchyard GJ. Antiretrovirals and isoniazid preventive therapy in the prevention of HIV-associated tuberculosis in settings with limited health-care resources. The Lancet infectious diseases 2010; 10(7): 489-98.50.Mills HL, Cohen T, Colijn C. Community-wide isoniazid preventive therapy drives drug-resistant tuberculosis: a model-based analysis. Science translational medicine 2013; 5(180): 180ra49.51.Jacobson KR, Theron D, Victor TC, Streicher EM, Warren RM, Murray MB. Treatment outcomes of isoniazid-resistant tuberculosis patients, Western Cape Province, South Africa. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2011; 53(4): 369-72.52.WHO. Macroeconomics and health: investing in health for economic development. Geneva, 2001.53.World Bank. GDP per capita (current US$). 2013. (accessed 11 May 2015 2015).54.Briggs AH, Weinstein MC, Fenwick EA, et al. Model parameter estimation and uncertainty analysis: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force Working Group-6. Med Decis Making 2012; 32(5): 722-32.55.Stinnett AA, Mullahy J. Net health benefits: a new framework for the analysis of uncertainty in cost-effectiveness analysis. Med Decis Making 1998; 18(2 Suppl): S68-80.56.WHO. Global Tuberculosis Report 2014. Geneva, Switzerland: WHO, 2014.57.Boehme CC, Nicol MP, Nabeta P, et al. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet 2011; 377(9776): 1495-505.58.Gandhi NR, Moll A, Sturm AW, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet 2006; 368(9547): 1575-80.59.South Africa Department of Health. The KZN "outbreak". Pretoria: DoH, 2006.60.Orenstein EW, Basu S, Shah NS, et al. Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. The Lancet infectious diseases 2009; 9(3): 153-61.61.Jacobson KR, Tierney DB, Jeon CY, Mitnick CD, Murray MB. Treatment outcomes among patients with extensively drug-resistant tuberculosis: systematic review and meta-analysis. 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Population Health Impact and Cost-Effectiveness of Tuberculosis Diagnosis with Xpert MTB/RIF: A Dynamic Simulation and Economic Evaluation. PLoS medicine 2012; 9(11): e1001347.67.Cleary S, Okorafor O, Chitha W, Boulle A, Jikwana S. South African Health Reveiw: Chapter 5 - Financing Antiretroviral Treatment and Primary Health Care Services. Durban: Health Systems Trust, 2005.68.Bassett IV, Giddy J, Nkera J, et al. Routine voluntary HIV testing in Durban, South Africa: the experience from an outpatient department. J Acquir Immune Defic Syndr 2007; 46(2): 181-6.69.Granich R, Kahn JG, Bennett R, et al. Expanding ART for treatment and prevention of HIV in South Africa: estimated cost and cost-effectiveness 2011-2050. PLoS One 2012; 7(2): e30216.70.Cleary S, Boulle A, McIntyre D, Coetzee D. Cost-Effectiveness of Antiretroviral Treatment for HIV-Positive Adults in a South African Township. Cape Town, South Africa: University of Cape Town, 2004.71.Akolo C, Adetifa I, Shepperd S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev 2010; (1): CD000171.72.Gupta S, Abimbola T, Date A, et al. Cost-effectiveness of the Three I's for HIV/TB and ART to prevent TB among people living with HIV. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 2014; 18(10): 1159-65.indasamy D, Kranzer K, van Schaik N, et al. Linkage to HIV, TB and non-communicable disease care from a mobile testing unit in Cape Town, South Africa. PLoS One 2013; 8(11): e80017.74.van Rooyen H, Barnabas RV, Baeten JM, et al. High HIV testing uptake and linkage to care in a novel program of home-based HIV counseling and testing with facilitated referral in KwaZulu-Natal, South Africa. J Acquir Immune Defic Syndr 2013; 64(1): e1-8.75.Lawn SD, Harries AD, Williams BG, et al. Antiretroviral therapy and the control of HIV-associated tuberculosis. Will ART do it? The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 2011; 15(5): 571-81.76.Havlir DV, Getahun H, Sanne I, Nunn P. Opportunities and challenges for HIV care in overlapping HIV and TB epidemics. JAMA : the journal of the American Medical Association 2008; 300(4): 423-30.77.WHO. Treatment of Tuberculosis Guidelines. Fourth edition. Geneva, Switzerlnd: WHO, 2010.78.Health Systems Trust. Defaulter (interruption) rate (new Sm+ cases) (%). 2013. (accessed 30 April 2013.79.Holtz TH, Lancaster J, Laserson KF, Wells CD, Thorpe L, Weyer K. Risk factors associated with default from multidrug-resistant tuberculosis treatment, South Africa, 1999-2001. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 2006; 10(6): 649-55.80.Shean KP, Willcox PA, Siwendu SN, et al. Treatment outcome and follow-up of multidrug-resistant tuberculosis patients, West Coast/Winelands, South Africa, 1992-2002. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 2008; 12(10): 1182-9.81.Gandhi NR, Moll AP, Lalloo U, et al. Successful integration of tuberculosis and HIV treatment in rural South Africa: the Sizonq'oba study. J Acquir Immune Defic Syndr 2009; 50(1): 37-43.82.Long EF, Brandeau ML, Owens DK. The cost-effectiveness and population outcomes of expanded HIV screening and antiretroviral treatment in the United States. Annals of internal medicine 2010; 153(12): 778-89.83.Boehme C, Nicol M, Nabeta P, et al. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet 2011; 377(9776): 1495-505.84.Health Systems Trust. Bacteriological coverage rate (%. 2013. (accessed 4 June 2013.85.Cobelens FG, Egwaga SM, van Ginkel T, Muwinge H, Matee MI, Borgdorff MW. Tuberculin skin testing in patients with HIV infection: limited benefit of reduced cutoff values. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2006; 43(5): 634-9.86.Republic of South Africa. National Consolidated Guidelines for the Prevention of Mother-to-Child Transmission of HIV (PMTCT) and the Management of HIV in Children, Adolescents and Adults. South Africa: Department of Health, 2014.Table I. Additional epidemiological model parameters, ranges, and references. Rates are in units of year-1 unless otherwise noted. *The extent to which ART mitigates the effect of HIV on the natural history of TB is quantified by the parameter k.ParameterSymbolTB Disease StatusHIV–HIV+ (No ART)HIV+ (ART)ReferenceAnnual population growth rateg0.0584 (0.04–0.06)NANA ADDIN EN.CITE <EndNote><Cite><Author>Actuarial Society of South Africa</Author><Year>2011</Year><RecNum>36</RecNum><DisplayText><style face="superscript">1,2,13</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">36</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>Actuarial Society of South Africa,</author></authors></contributors><titles><title>ASSA2008 Model</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite><Cite><Author>Gilbert</Author><Year>2015</Year><RecNum>93</RecNum><record><rec-number>93</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1429651825">93</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, J A</author><author>Long, E F</author><author>Brooks, R P</author><author>Friedland, G H</author><author>Moll, A P</author><author>Townsend, J P</author><author>Galvani, A P</author><author>Shenoi, S V</author></authors></contributors><titles><title>Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0126267</pages><volume>10</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>1,2,13Annual mortality rateBaseline (no TB)0.008(0.004–0.015)0.008 (0.004–0.015, CD4+>500),0.17 (0.1–0.5, CD4+≤500)0.008 (0.004–0.015, CD4+>500),0.056 (0.015–0.30, CD4+≤500)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY3R1YXJpYWwgU29jaWV0eSBvZiBTb3V0aCBBZnJpY2E8
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ADDIN EN.CITE.DATA 1,2,4,13TB transmissibility coefficientTB8.65 x 10-5 (8 x 10-5–1 x 10-4) 8.65 x 10-5 (8 x 10-5–1 x 10-4)8.65 x 10-5 (8 x 10-5–1 x 10-4) ADDIN EN.CITE <EndNote><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><DisplayText><style face="superscript">1,2,13</style></DisplayText><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite><Cite><Author>Actuarial Society of South Africa</Author><Year>2011</Year><RecNum>36</RecNum><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">36</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>Actuarial Society of South Africa,</author></authors></contributors><titles><title>ASSA2008 Model</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite><Cite><Author>Gilbert</Author><Year>2015</Year><RecNum>93</RecNum><record><rec-number>93</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1429651825">93</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, J A</author><author>Long, E F</author><author>Brooks, R P</author><author>Friedland, G H</author><author>Moll, A P</author><author>Townsend, J P</author><author>Galvani, A P</author><author>Shenoi, S V</author></authors></contributors><titles><title>Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0126267</pages><volume>10</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>1,2,13Relative fitness penalty drug resistance TB (proportion)h2MDR0.12 (0–0.7)0.12 (0–0.7)0.12 (0–0.7)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj
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dGU+PC9FbmROb3RlPgB=
ADDIN EN.CITE.DATA 4,23Endogenous annual TB reactivation rateLong latency0.00011 (0.0001–0.0003)0.17 (0.04–0.2)* PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 4,23Degree susceptibility despite prior TB infection (proportion)xTB0.35 (0.1–0.6)0.75 (0.5–1)*PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 4Baseline TB detection and treatment1.2917(0.9163–2.3026)1.2917(0.9163–2.3026)1.2917(0.9163–2.3026) ADDIN EN.CITE <EndNote><Cite><Author>Actuarial Society of South Africa</Author><Year>2011</Year><RecNum>36</RecNum><DisplayText><style face="superscript">1,2,13</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">36</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>Actuarial Society of South Africa,</author></authors></contributors><titles><title>ASSA2008 Model</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite><Cite><Author>Gilbert</Author><Year>2015</Year><RecNum>93</RecNum><record><rec-number>93</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1429651825">93</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, J A</author><author>Long, E F</author><author>Brooks, R P</author><author>Friedland, G H</author><author>Moll, A P</author><author>Townsend, J P</author><author>Galvani, A P</author><author>Shenoi, S V</author></authors></contributors><titles><title>Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0126267</pages><volume>10</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>1,2,13Proportion cured by 1st line TB drugsq11DS0.73 (0.65–0.88)0.58 (0.52–0.74)*PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 23Proportion defaulting from TB treatmentdTB1DS0.07 (0.048–0.088)0.07 (0.048–0.088)0.07 (0.048–0.088) ADDIN EN.CITE <EndNote><Cite><Author>Health Systems Trust</Author><Year>2013</Year><RecNum>105</RecNum><DisplayText><style face="superscript">78</style></DisplayText><record><rec-number>105</rec-number><foreign-keys><key app="EN" db-id="rtpevvxts09rrnevrr1v9rz022sr292zdwaw" timestamp="1435932532">105</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>Health Systems Trust,</author></authors></contributors><titles><title>Defaulter (interruption) rate (new Sm+ cases) (%)</title></titles><number>30 April 2013</number><dates><year>2013</year></dates><urls><related-urls><url> outpatient0.07 (0.048–0.088)0.07 (0.048–0.088)0.07 (0.048–0.088)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYWxsZW5ncmVuPC9BdXRob3I+PFllYXI+MjAxMTwvWWVh
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ADDIN EN.CITE.DATA 26,63,64Proportion of treated TB patients who acquire or amplify resistance1DS to MDR0.038 (0.025–0.1)0.038 (0.025–0.1)0.038 (0.025–0.1)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 42MDR to XDR0.030 (0.025–0.1)0.030 (0.025–0.1)0.030 (0.025–0.1)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 4Time to identification of TB treatment failure (months)1κ2 (1–4)2 (1–4)2 (1–4)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48UmVj
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 23Time from culture collection to MDR treatment initiation (days)1σDSDecentralized72 (56–99)72(56–99)72(56–99)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Mb3ZlZGF5PC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48
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ADDIN EN.CITE.DATA 46Proportion of cases defaulting before TB treatment initiationlTBDS/MDR outpatient (DOTS)0.15 (0–0.24)0.15 (0–0.24)0.15 (0–0.24) ADDIN EN.CITE <EndNote><Cite><Author>Dowdy</Author><Year>2008</Year><RecNum>81</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>81</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1428456678">81</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dowdy, D. W.</author><author>O'Brien, M. A.</author><author>Bishai, D.</author></authors></contributors><auth-address>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. david.w.dowdy@</auth-address><titles><title>Cost-effectiveness of novel diagnostic tools for the diagnosis of tuberculosis</title><secondary-title>Int J Tuberc Lung Dis</secondary-title></titles><periodical><full-title>Int J Tuberc Lung Dis</full-title><abbr-1>The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease</abbr-1></periodical><pages>1021-9</pages><volume>12</volume><number>9</number><keywords><keyword>Brazil</keyword><keyword>Cost-Benefit Analysis</keyword><keyword>Decision Support Techniques</keyword><keyword>Diagnostic Tests, Routine/*economics/methods</keyword><keyword>Humans</keyword><keyword>Kenya</keyword><keyword>Models, Economic</keyword><keyword>Sensitivity and Specificity</keyword><keyword>South Africa</keyword><keyword>Tuberculosis/*diagnosis/drug therapy/economics</keyword></keywords><dates><year>2008</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1027-3719 (Print)
1027-3719 (Linking)</isbn><accession-num>18713499</accession-num><urls><related-urls><url> inpatient0.5 (0.29–0.73)0.5 (0.29–0.73)0.5 (0.29–0.73) ADDIN EN.CITE <EndNote><Cite><Author>Republic of South Africa</Author><Year>2011</Year><RecNum>18</RecNum><DisplayText><style face="superscript">26</style></DisplayText><record><rec-number>18</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">18</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>Republic of South Africa,</author></authors></contributors><titles><title>Multi-Drug Resistant Tuberculosis. A Policy Framework on Decentralised and Deinstitutionalised Management for South Africa</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>26HIV transmissibility coefficientHIVNA1.67x10-6 (1 x 10-6–2 x 10-6)1.67x10-6(1 x 10-6–2 x 10-6) ADDIN EN.CITE <EndNote><Cite><Author>Actuarial Society of South Africa</Author><Year>2011</Year><RecNum>36</RecNum><DisplayText><style face="superscript">1,2,13</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">36</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>Actuarial Society of South Africa,</author></authors></contributors><titles><title>ASSA2008 Model</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite><Cite><Author>Gilbert</Author><Year>2015</Year><RecNum>93</RecNum><record><rec-number>93</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1429651825">93</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, J A</author><author>Long, E F</author><author>Brooks, R P</author><author>Friedland, G H</author><author>Moll, A P</author><author>Townsend, J P</author><author>Galvani, A P</author><author>Shenoi, S V</author></authors></contributors><titles><title>Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0126267</pages><volume>10</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>1,2,13 (HIV transmission shape parameter)NA4.31 (1–6)4.31 (1–6) ADDIN EN.CITE <EndNote><Cite><Author>Actuarial Society of South Africa</Author><Year>2011</Year><RecNum>36</RecNum><DisplayText><style face="superscript">1,2,13</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">36</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>Actuarial Society of South Africa,</author></authors></contributors><titles><title>ASSA2008 Model</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite><Cite><Author>Gilbert</Author><Year>2015</Year><RecNum>93</RecNum><record><rec-number>93</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1429651825">93</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, J A</author><author>Long, E F</author><author>Brooks, R P</author><author>Friedland, G H</author><author>Moll, A P</author><author>Townsend, J P</author><author>Galvani, A P</author><author>Shenoi, S V</author></authors></contributors><titles><title>Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0126267</pages><volume>10</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>1,2,13Relative infectivity of HIV on ART (proportion)xHIVNANA0.12 (0–0.12)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HYW5kaGk8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 1,2,13,82ART coverage (CD4+ < 500) NA52% (20–80%)NA ADDIN EN.CITE <EndNote><Cite><Author>Johnson</Author><Year>2012</Year><RecNum>47</RecNum><DisplayText><style face="superscript">31</style></DisplayText><record><rec-number>47</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">47</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Johnson, L. F.</author></authors></contributors><titles><title>Access to Antiretroviral Treatment in South Africa, 2004-2011</title><secondary-title>The Southern African Journal of HIV Medicine</secondary-title></titles><periodical><full-title>The Southern African Journal of HIV Medicine</full-title></periodical><pages>22-27</pages><volume>13</volume><number>1</number><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>31Proportion of cases detected defaulting before HIV treatment initiationlHIVScreening ProgramNA0.69(0.16–0.8)NAPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXNzZXR0PC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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ADDIN EN.CITE.DATA 41,42,73,74Proportion retained in HIV treatment over 3 yearsdHIVNANA0.75 (0.64–0.87)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gb3g8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 30Rate of relapse from chemotherapeutic cure0.001 (0–0.01)0.001 (0–0.01)0.001 (0–0.01)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 4Duration of HIV infection, CD4+ cell count >500 (years)1γNA4 (3–5); 2 (1–3, active TB infx)NAPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXJ0aW48L0F1dGhvcj48WWVhcj4xOTk1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 15,17,75,76Sensitivity of TB symptom screeningm69% (51.9–83.7%)79% (58.3–90.9%)79% (58.3–90.9%)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BeWxlczwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJl
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db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1437421229">136</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Boehme, Catharina</author><author>Nicol, Mark</author><author>Nabeta, Pamela</author><author>Michael, Joy</author><author>Gotuzzo, Eduardo</author><author>Tahirli, Rasim</author><author>Gler, Ma</author><author>Blakemore, Robert</author><author>Worodria, William</author><author>Gray, Christen</author><author>Huang, Laurence</author><author>Caceres, Tatiana</author><author>Mehdiyev, Rafail</author><author>Raymond, Lawrence</author><author>Whitelaw, Andrew</author><author>Sagadevan, Kalaiselvan</author><author>Alexander, Heather</author><author>Albert, Heidi</author><author>Cobelens, Frank</author><author>Cox, Helen</author><author>Alland, David</author><author>Perkins, Mark</author></authors></contributors><titles><title>Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study</title><secondary-title>Lancet</secondary-title></titles><periodical><full-title>Lancet</full-title><abbr-1>Lancet</abbr-1></periodical><pages>1495-1505</pages><volume>377</volume><number>9776</number><dates><year>2011</year></dates><isbn>0140-6736</isbn><urls><related-urls><url> of Xpert MTB/RIF for RIF resistance detection given MTB detectedy94.4% (90.8–98.6%)94.4% (90.8–98.6%)94.4% (90.8–98.6%) ADDIN EN.CITE <EndNote><Cite><Author>Boehme</Author><Year>2011</Year><RecNum>136</RecNum><DisplayText><style face="superscript">83</style></DisplayText><record><rec-number>136</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1437421229">136</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Boehme, Catharina</author><author>Nicol, Mark</author><author>Nabeta, Pamela</author><author>Michael, 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ADDIN EN.CITE.DATA 18-20Table II. Uncertainty distributions for model and cost parameters. All rates and probabilities are annual. The 95% confidence interval of gamma or beta distributions were fit to the parameter ranges in Table 1 and Table I. The shape a and scale b gamma distribution parameters are specified as Gamma(a,b), while the first shape a and second shape b beta distribution parameters are specified as Beta(a,b). *The extent to which ART mitigates the effect of HIV on the natural history of TB is quantified by the parameter k.ParameterSymbolTB Disease StatusHIV–HIV+ (No ART)HIV+ (ART)ReferenceAnnual population growth rategGamma(94, 0.0005)NANA ADDIN EN.CITE <EndNote><Cite><Author>Actuarial Society of South Africa</Author><Year>2011</Year><RecNum>36</RecNum><DisplayText><style face="superscript">1,2,13</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">36</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>Actuarial Society of South Africa,</author></authors></contributors><titles><title>ASSA2008 Model</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite><Cite><Author>Gilbert</Author><Year>2015</Year><RecNum>93</RecNum><record><rec-number>93</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1429651825">93</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, J A</author><author>Long, E F</author><author>Brooks, R P</author><author>Friedland, G H</author><author>Moll, A P</author><author>Townsend, J P</author><author>Galvani, A P</author><author>Shenoi, S V</author></authors></contributors><titles><title>Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0126267</pages><volume>10</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>1,2,13Annual mortality rateBaseline (no TB)Gamma(9, 9 x 10-4)Gamma(9, 9 x 10-4) (CD4+>500),Gamma(6, 0.04) (CD4+≤500)Gamma(9, 9 x 10-4) (CD4+>500),* (CD4+≤500)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY3R1YXJpYWwgU29jaWV0eSBvZiBTb3V0aCBBZnJpY2E8
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ADDIN EN.CITE.DATA 1,2,4,13TB transmissibility coefficientTBGamma(309,3 x 10-7)Gamma(309, 3 x 10-7)Gamma(309, 3 x 10-7) ADDIN EN.CITE <EndNote><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><DisplayText><style face="superscript">1,2,13</style></DisplayText><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite><Cite><Author>Actuarial Society of South Africa</Author><Year>2011</Year><RecNum>36</RecNum><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">36</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>Actuarial Society of South Africa,</author></authors></contributors><titles><title>ASSA2008 Model</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite><Cite><Author>Gilbert</Author><Year>2015</Year><RecNum>93</RecNum><record><rec-number>93</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1429651825">93</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, J A</author><author>Long, E F</author><author>Brooks, R P</author><author>Friedland, G H</author><author>Moll, A P</author><author>Townsend, J P</author><author>Galvani, A P</author><author>Shenoi, S V</author></authors></contributors><titles><title>Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0126267</pages><volume>10</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>1,2,13Relative fitness penalty drug resistance TB (proportion)h2MDRBeta(2, 4)Beta(2, 4)Beta(2, 4)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj
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dGU+PC9FbmROb3RlPgB=
ADDIN EN.CITE.DATA 4,23Endogenous annual TB reactivation rateLong latencyGamma(13, 1 x 10-5)Gamma(6, 0.02)* PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj
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a2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDA5PC95ZWFyPjxwdWItZGF0ZXM+PGRh
dGU+TWF5IDU8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4xMDkxLTY0OTAgKEVsZWN0
cm9uaWMpJiN4RDswMDI3LTg0MjQgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjE5MzY1
MDc2PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3Lm5j
YmkubmxtLm5paC5nb3YvcHVibWVkLzE5MzY1MDc2PC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxz
PjxjdXN0b20yPjI2Nzg2MTQ8L2N1c3RvbTI+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEw
NzMvcG5hcy4wODEyNDcyMTA2PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48L3JlY29yZD48L0Np
dGU+PC9FbmROb3RlPgB=
ADDIN EN.CITE.DATA 4,23Degree susceptibility despite prior TB infection (proportion)xTBBeta(4, 8)Beta(6, 2)*PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 4Proportion of TB infections that are infectiousfBeta(95, 70)Beta(20, 50)*PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 4Baseline TB detection and treatmentGamma(22, 0.07)Gamma(22, 0.07)Gamma(22, 0.07) ADDIN EN.CITE <EndNote><Cite><Author>Actuarial Society of South Africa</Author><Year>2011</Year><RecNum>36</RecNum><DisplayText><style face="superscript">1,2,13</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">36</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>Actuarial Society of South Africa,</author></authors></contributors><titles><title>ASSA2008 Model</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite><Cite><Author>Gilbert</Author><Year>2015</Year><RecNum>93</RecNum><record><rec-number>93</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1429651825">93</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, J A</author><author>Long, E F</author><author>Brooks, R P</author><author>Friedland, G H</author><author>Moll, A P</author><author>Townsend, J P</author><author>Galvani, A P</author><author>Shenoi, S V</author></authors></contributors><titles><title>Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0126267</pages><volume>10</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>1,2,13Proportion cured by 1st line TB drugsq11DSBeta(38, 11)Beta(46, 26)*PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 23Proportion defaulting from TB treatmentdTB1DSBeta(40, 554)Beta(40, 554)Beta(40, 554) ADDIN EN.CITE <EndNote><Cite><Author>Health Systems Trust</Author><Year>2013</Year><RecNum>105</RecNum><DisplayText><style face="superscript">78</style></DisplayText><record><rec-number>105</rec-number><foreign-keys><key app="EN" db-id="rtpevvxts09rrnevrr1v9rz022sr292zdwaw" timestamp="1435932532">105</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>Health Systems Trust,</author></authors></contributors><titles><title>Defaulter (interruption) rate (new Sm+ cases) (%)</title></titles><number>30 April 2013</number><dates><year>2013</year></dates><urls><related-urls><url> outpatientBeta(40, 554)Beta(40, 554)Beta(40, 554)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYWxsZW5ncmVuPC9BdXRob3I+PFllYXI+MjAxMTwvWWVh
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ADDIN EN.CITE.DATA 26,63,64Proportion of treated TB patients who acquire or amplify resistance1DS to MDRBeta(8, 134)Beta(8, 134)Beta(8, 134)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 42MDR to XDRBeta(8, 134)Beta(8, 134)Beta(8, 134)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXN1PC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 46Proportion of cases defaulting before TB treatment initiationlTBDS/MDR outpatient (DOTS)Beta(2, 2)Beta(2, 2)Beta(2, 2) ADDIN EN.CITE <EndNote><Cite><Author>Dowdy</Author><Year>2008</Year><RecNum>81</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>81</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1428456678">81</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dowdy, D. W.</author><author>O'Brien, M. A.</author><author>Bishai, D.</author></authors></contributors><auth-address>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. david.w.dowdy@</auth-address><titles><title>Cost-effectiveness of novel diagnostic tools for the diagnosis of tuberculosis</title><secondary-title>Int J Tuberc Lung Dis</secondary-title></titles><periodical><full-title>Int J Tuberc Lung Dis</full-title><abbr-1>The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease</abbr-1></periodical><pages>1021-9</pages><volume>12</volume><number>9</number><keywords><keyword>Brazil</keyword><keyword>Cost-Benefit Analysis</keyword><keyword>Decision Support Techniques</keyword><keyword>Diagnostic Tests, Routine/*economics/methods</keyword><keyword>Humans</keyword><keyword>Kenya</keyword><keyword>Models, Economic</keyword><keyword>Sensitivity and Specificity</keyword><keyword>South Africa</keyword><keyword>Tuberculosis/*diagnosis/drug therapy/economics</keyword></keywords><dates><year>2008</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1027-3719 (Print)
1027-3719 (Linking)</isbn><accession-num>18713499</accession-num><urls><related-urls><url> inpatientBeta(9, 9)Beta(9, 9)Beta(9, 9) ADDIN EN.CITE <EndNote><Cite><Author>Republic of South Africa</Author><Year>2011</Year><RecNum>18</RecNum><DisplayText><style face="superscript">26</style></DisplayText><record><rec-number>18</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">18</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>Republic of South Africa,</author></authors></contributors><titles><title>Multi-Drug Resistant Tuberculosis. A Policy Framework on Decentralised and Deinstitutionalised Management for South Africa</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>26HIV transmissibility coefficientHIVNAGamma(32, 4x10-8)Gamma(32, 4x10-8) ADDIN EN.CITE <EndNote><Cite><Author>Actuarial Society of South Africa</Author><Year>2011</Year><RecNum>36</RecNum><DisplayText><style face="superscript">1,2,13</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">36</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>Actuarial Society of South Africa,</author></authors></contributors><titles><title>ASSA2008 Model</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite><Cite><Author>Gilbert</Author><Year>2015</Year><RecNum>93</RecNum><record><rec-number>93</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1429651825">93</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, J A</author><author>Long, E F</author><author>Brooks, R P</author><author>Friedland, G H</author><author>Moll, A P</author><author>Townsend, J P</author><author>Galvani, A P</author><author>Shenoi, S V</author></authors></contributors><titles><title>Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0126267</pages><volume>10</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>1,2,13 (HIV transmission shape parameter)NAGamma(5, 0.6)Gamma(5, 0.6) ADDIN EN.CITE <EndNote><Cite><Author>Actuarial Society of South Africa</Author><Year>2011</Year><RecNum>36</RecNum><DisplayText><style face="superscript">1,2,13</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">36</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>Actuarial Society of South Africa,</author></authors></contributors><titles><title>ASSA2008 Model</title></titles><dates><year>2011</year></dates><urls></urls></record></Cite><Cite><Author>WHO</Author><Year>2014</Year><RecNum>38</RecNum><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">38</key></foreign-keys><ref-type name="Dataset">59</ref-type><contributors><authors><author>WHO,</author></authors></contributors><titles><title>WHO TB Burden Estimates</title></titles><dates><year>2014</year></dates><urls></urls></record></Cite><Cite><Author>Gilbert</Author><Year>2015</Year><RecNum>93</RecNum><record><rec-number>93</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1429651825">93</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, J A</author><author>Long, E F</author><author>Brooks, R P</author><author>Friedland, G H</author><author>Moll, A P</author><author>Townsend, J P</author><author>Galvani, A P</author><author>Shenoi, S V</author></authors></contributors><titles><title>Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0126267</pages><volume>10</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>1,2,13Relative infectivity of HIV on ART (proportion)xHIVNANABeta(2, 37)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HYW5kaGk8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 1,2,13,82ART coverage (CD4+ < 500) NAGamma(156, 0.005)NA ADDIN EN.CITE <EndNote><Cite><Author>Johnson</Author><Year>2012</Year><RecNum>47</RecNum><DisplayText><style face="superscript">31</style></DisplayText><record><rec-number>47</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">47</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Johnson, L. F.</author></authors></contributors><titles><title>Access to Antiretroviral Treatment in South Africa, 2004-2011</title><secondary-title>The Southern African Journal of HIV Medicine</secondary-title></titles><periodical><full-title>The Southern African Journal of HIV Medicine</full-title></periodical><pages>22-27</pages><volume>13</volume><number>1</number><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>31Proportion of cases detected defaulting before HIV treatment initiationlHIVScreening ProgramNABeta(8, 15)NAPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXNzZXR0PC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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ADDIN EN.CITE.DATA 4Duration of HIV infection, CD4+ cell count >500γNAGamma(59, 0.004) (no TB), Gamma(13, 0.05) (TB disease)NAPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXJ0aW48L0F1dGhvcj48WWVhcj4xOTk1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 57Specificity rapid HIV testNABeta(223, 2)NA ADDIN EN.CITE <EndNote><Cite><Author>Branson</Author><Year>2003</Year><RecNum>53</RecNum><DisplayText><style face="superscript">47</style></DisplayText><record><rec-number>53</rec-number><foreign-keys><key app="EN" db-id="t2tw25spi952swep9ta5pws4a2pr25f90ppe" timestamp="1424753038">53</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Branson, D.M.</author></authors></contributors><titles><title>Point-of-Care Rapid Tests for HIV Antibodies</title><secondary-title>J Lab Med</secondary-title></titles><periodical><full-title>J Lab Med</full-title></periodical><pages>288-295</pages><volume>27</volume><dates><year>2003</year></dates><urls></urls></record></Cite></EndNote>47Table III. Epidemiological Impacts. Epidemiological impact of community-based TB/HIV screening and linkage to care at frequencies of once every 2 years (Screen 2 yr), 1 year (Screen 1 yr), and 6 months (Screen 6 mo) relative to status quo with 36/12 months of IPT (IPT 36/12) or lifelong IPT (life IPT) on total TB incidence, HIV incidence (%), MDR-TB incidence, and XDR-TB incidence over 10 years.20152016201720182019202020212022202320242025TB incidence per 100,000 Status Quo, IPT 36/12868713598533485447417392371353338 Screen 2 yr, IPT 36/12868689550479430395368347329313299 Screen 1 yr, IPT 36/12868667509435389357333314298284272 Screen 6 mo, IPT 36/12868629445373331305285270257246235 Status Quo, IPT life868706569486427384351326306290276 Screen 2 yr, IPT life8686795104143513092802592432312211 Screen 1 yr, IPT life868655461359299261236219206197189 Screen 6 mo, IPT life868613387286233204186175167160155HIV incidence (%) Status Quo, IPT 36/121.01.01.01.01.00.90.90.90.90.90.8 Screen 2 yr, IPT 36/121.01.01.00.90.90.90.80.80.80.80.8 Screen 1 yr, IPT 36/121.01.00.90.90.80.80.80.80.80.70.7 Screen 6 mo, IPT 36/121.01.00.90.80.80.70.70.70.70.70.7 Status Quo, IPT life1.01.01.01.01.00.90.90.90.90.90.8 Screen 2 yr, IPT life1.01.01.00.90.90.80.80.80.80.80.7 Screen 1 yr, IPT life1.01.00.90.80.80.80.70.70.70.70.7 Screen 6 mo, IPT life1.01.00.80.80.70.70.70.60.60.60.6MDR-TB incidence per 100,000 Status Quo, IPT 36/125546363127252321201918 Screen 2 yr, IPT 36/125545352926232120191817 Screen 1 yr, IPT 36/125544332824222019171716 Screen 6 mo, IPT 36/125543312622201817161514 Status Quo, IPT life5545363027242221201918 Screen 2 yr, IPT life5545342824222019181716 Screen 1 yr, IPT life5544332723211917161615 Screen 6 mo, IPT life5542302421191716151413XDR-TB incidence per 100,000 Status Quo, IPT 36/1212121098777666 Screen 2 yr, IPT 36/1212111088776666 Screen 1 yr, IPT 36/121211987766655 Screen 6 mo, IPT 36/121211977665555 Status Quo, IPT life12121088776666 Screen 2 yr, IPT life1211987666555 Screen 1 yr, IPT life1211977665555 Screen 6 mo, IPT life1211876555544Table IV. Modeled Disease States.Disease StateDescriptionTBSSusceptiblePSSusceptible receiving IPTLLatent infection, slowELatent infection, fastPLLatent infection receiving IPTAActive infectionTActive infection on effective TB treatmentFActive infection in ineffective TB treatmentDActive infection detected and awaiting culture/DST resultsRRecoveredPRRecovered receiving IPTHIVSSusceptibleIInfected, CD4+ cell count > 500 cells/mlEInfected, CD4+ cell count ≤ 500 cells/mlICareInfected, not on ART, in HIV care at a CD4+ cell count > 500 cells/mlIARTInfected and on ART at CD4+ cell count > 500 cells/mlEARTInfected and on ART at CD4+ cell count ≤ 500 cells/mlFigure I. Model diagrams. Model diagrams of (A) TB transmission dynamics and (B) HIV transmission dynamics. Although depicted separately, modeled individuals had a status for each disease. Drug resistance (i.e., drug susceptible [DS], multidrug-resistant [MDR], and extensively drug-resistant [XDR] TB) was also included in the model. Model parameters and equations are detailed in S1 Text.Figure II. TB Diagnosis and Treatment Pathway Diagrams. Flow diagram depicting TB diagnosis and treatment within the model for (A) community-based TB/HIV screening and (B) standard of care.ABFigure III. HIV Diagnosis and Treatment Pathway Diagrams. Flow diagram depicting HIV diagnosis and treatment within the model for (A) community-based TB/HIV screening and (B) standard of care.ABFigure IV. Epidemiological impact when ART eligibility expanded to all HIV-infected individuals. Impact of annual community-based TB/HIV screening and linkage to care (Annual Screen) relative to status quo (Status Quo) with 36/12 months of IPT (IPT 36/12) or lifelong IPT (IPT life) on (A) total TB incidence, (B) HIV incidence (%), (C) MDR-TB incidence, and (D) XDR-TB incidence over 10 years when ART eligibility expanded to all individuals with HIV.ABCD ................
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