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Objective: To present evidence on the total costs and unit costs of delivering six integrated sexual reproductive health and HIV services in a high and medium HIV prevalence setting, in order to support policy makers and planners scaling up these essential services., Design: A retrospective facility based costing study conducted in 40 non-government organization and public health facilities in Kenya and Swaziland., Methods: Economic and financial costs were collected retrospectively for the year 2010/11, from each study site with an aim to estimate the cost per visit of six integrated HIV and SRH services. A full cost analysis using a combination of bottom-up and step-down costing methods was conducted from the health provider's perspective. The main unit of analysis is the economic unit cost per visit for each service. Costs are converted to 2013 International dollars., Results: The mean cost per visit for the HIV/SRH services ranged from $Int 14.23 (PNC visit) to $Int 74.21 (HIV treatment visit). We found considerable variation in the unit costs per visit across settings with family planning services exhibiting the least variation ($Int 6.71-52.24) and STI treatment and HIV treatment visits exhibiting the highest variation in unit cost ranging from ($Int 5.44-281.85) and ($Int 0.83-314.95), respectively. Unit costs of visits were driven by fixed costs while variability in visit costs across facilities was explained mainly by technology used and service maturity., Conclusion: For all services, variability in unit costs and cost components suggest that potential exists to reduce costs through better use of both human and capital resources, despite the high proportion of expenditure on drugs and medical supplies. Further work is required to explore the key drivers of efficiency and interventions that may facilitate efficiency improvements.

Background: If trained, equipped and utilised, community health workers (CHWs) delivering integrated community case management for sick children can potentially reduce child deaths by 60%. However, it is essential to maintain CHW motivation and performance. The inSCALE project aims to evaluate, using a cluster randomised controlled trial, the effect of interventions to increase CHW supervision and performance on the coverage of appropriate treatment for children with diarrhoea, pneumonia and malaria., Methods/design: Participatory methods were used to identify best practices and innovative solutions. Quantitative community based baseline surveys were conducted to allow restricted randomisation of clusters into intervention and control arms. Individual informed consent was obtained from all respondents. Following formative research and stakeholder consultations, two intervention packages were developed in Uganda and one in Mozambique. In Uganda, approximately 3,500 CHWs in 39 clusters were randomised into a mobile health (mHealth) arm, a participatory community engagement arm and a control arm. In Mozambique, 275 CHWs in 12 clusters were randomised into a mHealth arm and a control arm. The mHealth interventions encompass three components: 1) free phone communication between users; 2) data submission using phones with automated feedback, messages to supervisors for targeted supervision, and online data access for district statisticians; and 3) motivational messages. The community engagement arm in Uganda established village health clubs seeking to 1) improve the status and standing of CHWs, 2) increase demand for health services and 3) communicate that CHWs' work is important. Process evaluation was conducted after 10 months and end-line surveys will establish impact after 12 months in Uganda and 18 months in Mozambique. Main outcomes include proportion of sick children appropriately treated, CHW performance and motivation, and cost effectiveness of interventions., Discussion: Study strengths include a user-centred design to the innovations, while weaknesses include the lack of a robust measurement of coverage of appropriate treatment. Evidence of cost-effective innovations that increase motivation and performance of CHWs can potentially increase sustainable coverage of iCCM at scale., Trial Registration: (identifier NCT01972321 ) on 22 April 22 2013.

Social protection against the cost of illness is a central policy objective of Universal Health Coverage and the post-2015 Global strategy for Tuberculosis (TB). Understanding the economic burden associated with TB illness and care is key to identifying appropriate interventions towards achieving this target. The aims of this study were to identify points in patient pathways from start of TB symptoms to treatment completion where interventions could be targeted to reduce the economic impact on patients and households, and to identify those most vulnerable to these costs. Two cohorts of patients accessing TB services from ten clinics in four provinces in South Africa were surveyed between July 2012 and June 2013. One cohort of 351 people with suspected TB were interviewed at the point of receiving a TB diagnostic and followed up six months later. Another cohort of 168 patients on TB treatment, at the same ten facilities, was interviewed at two-months and five-months on treatment. Patients were asked about their health-seeking behaviour, associated costs, income loss, and coping strategies used. Patients incurred the greatest share of TB episode costs (41%) prior to starting treatment, with the largest portion of these costs being due to income loss. Poorer patients incurred higher direct costs during treatment than those who were less poor but only 5% of those interviewed were accessing cash-transfers during treatment. Indirect costs accounted for 52% of total episode cost. Despite free TB diagnosis and care in South Africa, patients incur substantial direct and indirect costs particularly prior to starting treatment. The poorest group of patients were incurring higher costs, with fewer resources to pay for it. Both the direct and indirect cost of illness should be taken into account when setting levels of financial protection and social support, to prevent TB illness from pushing the poor further into poverty., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Governments and donors are investing considerable resources on HIV prevention in order to scale up these services rapidly. Given the current economic climate, providers of HIV prevention services increasingly need to demonstrate that these investments offer good 'value for money'. One of the primary routes to achieve efficiency is to take advantage of economies of scale (a reduction in the average cost of a health service as provision scales-up), yet empirical evidence on economies of scale is scarce. Methodologically, the estimation of economies of scale is hampered by several statistical issues preventing causal inference and thus making the estimation of economies of scale complex. In order to estimate unbiased economies of scale when scaling up HIV prevention services, we apply our analysis to one of the few HIV prevention programmes globally delivered at a large scale: the Indian Avahan initiative. We costed the project by collecting data from the 138 Avahan NGOs and the supporting partners in the first four years of its scale-up, between 2004 and 2007. We develop a parsimonious empirical model and apply a system Generalized Method of Moments (GMM) and fixed-effects Instrumental Variable (IV) estimators to estimate unbiased economies of scale. At the programme level, we find that, after controlling for the endogeneity of scale, the scale-up of Avahan has generated high economies of scale. Our findings suggest that average cost reductions per person reached are achievable when scaling-up HIV prevention in low and middle income countries., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: In 2004, the largest HIV prevention project (Avahan) conducted globally was implemented in India. Avahan was implemented by NGOs supported by state lead partners in order to provide HIV prevention services to high-risk population groups. In 2007, most of the NGOs reached full coverage., Methods: Using a panel data set of the NGOs that implemented Avahan, we investigate the level of technical efficiency as well as the drivers of technical inefficiency by using the double bootstrap procedure developed by Simar & Wilson (2007). Unlike the two-stage traditional method, this method allows valid inference in the presence of measurement error and serial correlation., Results: We find that over the 4 years, Avahan NGOs could have reduced the level of inputs by 43% given the level of outputs reached. We find that efficiency of the project has increased over time. Results indicate that main drivers of inefficiency come from the characteristics of the state lead partner, the NGOs and the catchment area., Conclusion: These organisational factors are important to explicitly consider and assess when designing and implementing HIV prevention programmes and in setting benchmarks in order to optimise the use and allocation of resources., Jel Classifications: C14, I1.

Background: Early mortality for HIV-positive people starting antiretroviral therapy (ART) remains high in resource-limited settings, with tuberculosis the most important cause. Existing rapid diagnostic tests for tuberculosis lack sensitivity among HIV-positive people, and consequently, tuberculosis treatment is either delayed or started empirically (without bacteriological confirmation). We developed a management algorithm for ambulatory HIV-positive people, based on body mass index and point-of-care tests for haemoglobin and urine lipoarabinomannan (LAM), to identify those at high risk of tuberculosis and mortality. We designed a clinical trial to test whether implementation of this algorithm reduces six-month mortality among HIV-positive people with advanced immunosuppression., Methods/design: The TB Fast Track study is an open, pragmatic, cluster randomised superiority trial, with 24 primary health clinics randomised to implement the intervention or standard of care. Adults (aged ≥18 years) with a CD4 count of 150 cells/μL or less, who have not received any tuberculosis treatment in the last three months, or ART in the last six months, are eligible. In intervention clinics, the study algorithm is used to classify individuals as at high, medium or low probability of tuberculosis. Those classified as high probability start tuberculosis treatment immediately, followed by ART after two weeks. Medium-probability patients follow the South African guidelines for test-negative tuberculosis and are reviewed within a week, to be re-categorised as low or high probability. Low-probability patients start ART as soon as possible. The primary outcome is all-cause mortality at six months. Secondary outcomes include severe morbidity, time to ART start and cost-effectiveness., Discussion: This trial will test whether a primary care-friendly management algorithm will enable nurses to identify HIV-positive patients at the highest risk of tuberculosis, to facilitate prompt treatment and reduce early mortality. There remains an urgent need for better diagnostic tests for tuberculosis, especially for people with advanced HIV disease, which may render empirical treatment unnecessary., Trial Registration: This trial was registered with Current Controlled Trials (identifier: ISRCTN35344604 ) on 12 September 2012.

Introduction: Harmful gender norms and inequalities, including gender-based violence, are important structural barriers to effective HIV programming. We assess current evidence on what forms of gender-responsive intervention may enhance the effectiveness of basic HIV programmes and be cost-effective., Methods: Effective intervention models were identified from an existing evidence review ("what works for women"). Based on this, we conducted a systematic review of published and grey literature on the costs and cost-effectiveness of each intervention identified. Where possible, we compared incremental costs and effects., Results: Our effectiveness search identified 36 publications, reporting on the effectiveness of 22 HIV interventions with a gender focus. Of these, 11 types of interventions had a corresponding/comparable costing or cost-effectiveness study. The findings suggest that couple counselling for the prevention of vertical transmission; gender empowerment, community mobilization, and female condom promotion for female sex workers; expanded female condom distribution for the general population; and post-exposure HIV prophylaxis for rape survivors are cost-effective HIV interventions. Cash transfers for schoolgirls and school support for orphan girls may also be cost-effective in generalized epidemic settings., Conclusions: There has been limited research to assess the cost-effectiveness of interventions that seek to address women's needs and transform harmful gender norms. Our review identified several promising, cost-effective interventions that merit consideration as critical enablers in HIV investment approaches, as well as highlight that broader gender and development interventions can have positive HIV impacts. By no means an exhaustive package, these represent a first set of interventions to be included in the investment framework.

To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in low- and middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, to prevent active TB in all individuals, to have a 5-y to lifetime duration of protection, to have 40-80% efficacy, and to be targeted at "infants" or "adolescents/adults." Vaccine prices were tiered by income group (US $1.50-$10 per dose), and cost-effectiveness was assessed using incremental cost per disability adjusted life year (DALY) averted compared against gross national income per capita. Our results suggest that over 2024-2050, a vaccine targeted to adolescents/adults could have a greater impact than one targeted at infants. In low-income countries, a vaccine with a 10-y duration and 60% efficacy targeted at adolescents/adults could prevent 17 (95% range: 11-24) million TB cases by 2050 and could be considered cost-effective at $149 (cost saving to $387) per DALY averted. If targeted at infants, 0.89 (0.42-1.58) million TB cases could be prevented at $1,692 ($634-$4,603) per DALY averted. This profile targeted at adolescents/adults could be cost-effective at $4, $9, and $20 per dose in low-, lower-middle-, and upper-middle-income countries, respectively. Increased investments in adult-targeted TB vaccines may be warranted, even if only short duration and low efficacy vaccines are likely to be feasible, and trials among adults should be powered to detect low efficacies.

Introduction: The field of diagnostics for active tuberculosis (TB) is rapidly developing. TB diagnostic modeling can help to inform policy makers and support complicated decisions on diagnostic strategy, with important budgetary implications. Demand for TB diagnostic modeling is likely to increase, and an evaluation of current practice is important. We aimed to systematically review all studies employing mathematical modeling to evaluate cost-effectiveness or epidemiological impact of novel diagnostic strategies for active TB., Methods: Pubmed, personal libraries and reference lists were searched to identify eligible papers. We extracted data on a wide variety of model structure, parameter choices, sensitivity analyses and study conclusions, which were discussed during a meeting of content experts., Results & Discussion: From 5619 records a total of 36 papers were included in the analysis. Sixteen papers included population impact/transmission modeling, 5 were health systems models, and 24 included estimates of cost-effectiveness. Transmission and health systems models included specific structure to explore the importance of the diagnostic pathway (n = 4), key determinants of diagnostic delay (n = 5), operational context (n = 5), and the pre-diagnostic infectious period (n = 1). The majority of models implemented sensitivity analysis, although only 18 studies described multi-way sensitivity analysis of more than 2 parameters simultaneously. Among the models used to make cost-effectiveness estimates, most frequent diagnostic assays studied included Xpert MTB/RIF (n = 7), and alternative nucleic acid amplification tests (NAATs) (n = 4). Most (n = 16) of the cost-effectiveness models compared new assays to an existing baseline and generated an incremental cost-effectiveness ratio (ICER)., Conclusion: Although models have addressed a small number of important issues, many decisions regarding implementation of TB diagnostics are being made without the full benefits of insight from mathematical models. Further models are needed that address a wider array of diagnostic and epidemiological settings, that explore the inherent uncertainty of models and that include additional epidemiological data on transmission implications of false-negative diagnosis and the pre-diagnostic period.

Background: Most HIV prevention for female sex workers (FSWs) focuses on individual behaviour change involving peer educators, condom promotion and the provision of sexual health services. However, there is a growing recognition of the need to address broader societal, contextual and structural factors contributing to FSW risk behaviour. We assess the cost-effectiveness of adding community mobilisation (CM) and empowerment interventions (eg. community mobilisation, community involvement in programme management and services, violence reduction, and addressing legal policies and police practices), to core HIV prevention services delivered as part of Avahan in two districts (Bellary and Belgaum) of Karnataka state, Southern India., Methods: An ingredients approach was used to estimate economic costs in US$ 2011 from an HIV programme perspective of CM and empowerment interventions over a seven year period (2004-2011). Incremental impact, in terms of HIV infections averted, was estimated using a two-stage process. An 'exposure analysis' explored whether exposure to CM was associated with FSW's empowerment, risk behaviours and HIV/STI prevalence. Pathway analyses were then used to estimate the extent to which behaviour change may be attributable to CM and to inform a dynamic HIV transmission model., Findings: The incremental costs of CM and empowerment were US$ 307,711 in Belgaum and US$ 592,903 in Bellary over seven years (2004-2011). Over a 7-year period (2004-2011) the mean (standard deviation, sd.) number of HIV infections averted through CM and empowerment is estimated to be 1257 (308) in Belgaum and 2775 (1260) in Bellary. This translates in a mean (sd.) incremental cost per disability adjusted life year (DALY) averted of US$ 14.12 (3.68) in Belgaum and US$ 13.48 (6.80) for Bellary--well below the World Health Organisation recommended willingness to pay threshold for India. When savings from ART are taken into account, investments in CM and empowerment are cost saving., Conclusions: Our findings suggest that CM and empowerment is, at worst, highly cost-effective and, at best, a cost-saving investment from an HIV programme perspective. CM and empowerment interventions should therefore be considered as core components of HIV prevention programmes for FSWs.

Background: The Avahan programme has provided HIV prevention activities, including condom promotion, to female sex workers (FSWs) in southern India since 2004. Evidence suggests Avahan averted 202,000 HIV infections over 4 years. For replicating this intervention elsewhere, it is essential to understand how the intervention's impact could have been optimised for different budget levels., Methods: Behavioural data were used to determine how condom use varied for FSWs with different levels of intervention intensity. Cost data from 64 Avahan districts quantified how district-level costs related to intervention scale and intensity. A deterministic model for HIV transmission amongst FSWs and clients projected the impact and cost of intervention strategies for different scale and intensity, and identified the optimal strategies that maximise impact for different budget levels., Results: As budget levels increase, the optimal intervention strategy is to first increase intervention intensity which achieves little impact, then scale-up coverage to high levels for large increases in impact, and lastly increase intensity further for small additional gains. The cost-effectiveness of these optimal strategies generally improves with increasing resources, while straying from these strategies can triple costs for the same impact. Projections suggest Avahan was close to being optimal, and moderate budget reductions (≥ 20%) would have reduced impact considerably (>40%)., Discussion: Our analysis suggests that tailoring the design of HIV prevention programmes for FSWs can improve impact, and that a certain level of resources are required to achieve demonstrable impact. These insights are critical for optimising the use of limited resources for preventing HIV.

Objective: The study objective is to measure, analyse costs of scaling up HIV prevention for high-risk groups in India, in order to assist the design of future HIV prevention programmes in South Asia and beyond., Design: Prospective costing study., Methods: This study is one of the most comprehensive studies of the costs of HIV prevention for high-risk groups to date in both its scope and size. HIV prevention included outreach, sexually transmitted infections (STI) services, condom provision, expertise enhancement, community mobilisation and enabling environment activities. Economic costs were collected from 138 non-government organisations (NGOs) in 64 districts, four state level lead implementing partners (SLPs), and the national programme level (Bill and Melinda Gates Foundation (BMGF)) office over four years using a top down costing approach, presented in US$ 2011., Results: Mean total unit costs (2004-08) per person reached at least once a year and per monthly contact were US$ 235(56-1864) and US$ 82(12-969) respectively. 35% of the cost was incurred by NGOs, 30% at the state level SLP and 35% at the national programme level. The proportion of total costs by activity were 34% for expertise enhancement, 37% for programme management (including support and supervision), 22% for core HIV prevention activities (outreach and STI services) and 7% for community mobilisation and enabling environment activities. Total unit cost per person reached fell sharply as the programme expanded due to declining unit costs above the service level (from US$ 477 per person reached in 2004 to US$ 145 per person reached in 2008). At the service level also unit costs decreased slightly over time from US$ 68 to US$ 64 per person reached., Conclusions: Scaling up HIV prevention for high risk groups requires significant investment in expertise enhancement and programme administration. However, unit costs decreased with programme expansion in spite of an increase in the scope of activities.

Background: Avahan is a large-scale, HIV preventive intervention, targeting high-risk populations in south India. We assessed the cost-effectiveness of Avahan to inform global and national funding institutions who are considering investing in worldwide HIV prevention in concentrated epidemics., Methods: We estimated cost effectiveness from a programme perspective in 22 districts in four high-prevalence states. We used the UNAIDS Costing Guidelines for HIV Prevention Strategies as the basis for our costing method, and calculated effect estimates using a dynamic transmission model of HIV and sexually transmitted disease transmission that was parameterised and fitted to locally observed behavioural and prevalence trends. We calculated incremental cost-effective ratios (ICERs), comparing the incremental cost of Avahan per disability-adjusted life-year (DALY) averted versus a no-Avahan counterfactual scenario. We also estimated incremental cost per HIV infection averted and incremental cost per person reached., Findings: Avahan reached roughly 150 000 high-risk individuals between 2004 and 2008 in the 22 districts studied, at a mean cost per person reached of US$327 during the 4 years. This reach resulted in an estimated 61 000 HIV infections averted, with roughly 11 000 HIV infections averted in the general population, at a mean incremental cost per HIV infection averted of $785 (SD 166). We estimate that roughly 1 million DALYs were averted across the 22 districts, at a mean incremental cost per DALY averted of $46 (SD 10). Future antiretroviral treatment (ART) cost savings during the lifetime of the cohort exposed to HIV prevention were estimated to be more than $77 million (compared with the slightly more than $50 million spent on Avahan in the 22 districts during the 4 years of the study)., Interpretation: This study provides evidence that the investment in targeted HIV prevention programmes in south India has been cost effective, and is likely to be cost saving if a commitment is made to provide ART to all that can benefit from it. Policy makers should consider funding and sustaining large-scale targeted HIV prevention programmes in India and beyond., Funding: Bill & Melinda Gates Foundation., (Copyright © 2014 Vassall et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by .. All rights reserved.)

Background: There is growing interest in integration of HIV and sexual and reproductive health (SRH) services as a way to improve the efficiency of human resources (HR) for health in low- and middle-income countries. Although this is supported by a wealth of evidence on the acceptability and clinical effectiveness of service integration, there is little evidence on whether staff in general health services can easily absorb HIV services., Methods: We conducted a descriptive analysis of HR integration through task shifting/sharing and staff workload in the context of the Integra Initiative - a large-scale five-year evaluation of HIV/SRH integration. We describe the level, characteristics and changes in HR integration in the context of wider efforts to integrate HIV/SRH, and explore the impact of HR integration on staff workload., Results: Improvements in the range of services provided by staff (HR integration) were more likely to be achieved in facilities which also improved other elements of integration. While there was no overall relationship between integration and workload at the facility level, HIV/SRH integration may be most influential on staff workload for provider-initiated HIV testing and counselling (PITC) and postnatal care (PNC) services, particularly where HIV care and treatment services are being supported with extra SRH/HIV staffing. Our findings therefore suggest that there may be potential for further efficiency gains through integration, but overall the pace of improvement is slow., Conclusions: This descriptive analysis explores the effect of HIV/SRH integration on staff workload through economies of scale and scope in high- and medium-HIV prevalence settings. We find some evidence to suggest that there is potential to improve productivity through integration, but, at the same time, significant challenges are being faced, with the pace of productivity gain slow. We recommend that efforts to implement integration are assessed in the broader context of HR planning to ensure that neither staff nor patients are negatively impacted by integration policy.

Objective: To synthesize the data available--on costs, efficiency and economies of scale and scope--for the six basic programmes of the UNAIDS Strategic Investment Framework, to inform those planning the scale-up of human immunodeficiency virus (HIV) services in low- and middle-income countries., Methods: The relevant peer-reviewed and "grey" literature from low- and middle-income countries was systematically reviewed. Search and analysis followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines., Findings: Of the 82 empirical costing and efficiency studies identified, nine provided data on economies of scale. Scale explained much of the variation in the costs of several HIV services, particularly those of targeted HIV prevention for key populations and HIV testing and treatment. There is some evidence of economies of scope from integrating HIV counselling and testing services with several other services. Cost efficiency may also be improved by reducing input prices, task shifting and improving client adherence., Conclusion: HIV programmes need to optimize the scale of service provision to achieve efficiency. Interventions that may enhance the potential for economies of scale include intensifying demand-creation activities, reducing the costs for service users, expanding existing programmes rather than creating new structures, and reducing attrition of existing service users. Models for integrated service delivery--which is, potentially, more efficient than the implementation of stand-alone services--should be investigated further. Further experimental evidence is required to understand how to best achieve efficiency gains in HIV programmes and assess the cost-effectiveness of each service-delivery model.

Background and Objectives: The global architecture for providing development assistance for health (DAH) has become increasing complex in the last decade, with many new funding agencies entering the health sector. This study presents a detailed picture of European Union (EU) and EU member state originating DAH between 2006 and 2009; with a specific focus on assessing the extent of complementarity of development assistance sourced from the EU., Design: We use a combination of internal EU reporting systems, OECD-DAC creditor reporting system data and other data sources to estimate DAH flows. Our method uses a line by line project assessment in order to identify and categorise DAH flows., Results and Conclusions: Our findings show a complex picture of DAH flows--from source, to channel of assistance, to channel of implementation--that is hard to track at the global level, and rarely comprehensively and regularly tracked at the country level. While the majority of EU DAH is focused on low and lower middle income countries there also remains much disparity between countries; and further analysis is required to better understand whether these imbalances are fair and efficient; or result in overlap. We also recommend investment in quality control of DAH tracking internally within donor agencies, and investment in the development of country based systems in order to enable countries and development partners better harmonise DAH flows.

Objective: Structural interventions can reduce HIV vulnerability. However, HIV-specific budgeting, based on HIV-specific outcomes alone, could lead to the undervaluation of investments in such interventions and suboptimal resource allocation. We investigate this hypothesis by examining the consequences of alternative financing approaches., Methods: We compare three approaches for deciding whether to finance a structural intervention to keep adolescent girls in school in Malawi. In the first, HIV and non-HIV budget holders participate in a cross-sectoral cost-benefit analysis and fund the intervention if the benefits outweigh the costs. In the second silo approach, each budget holder considers the cost-effectiveness of the intervention in terms of their own objectives and funds the intervention on the basis of their sector-specific thresholds of what is cost-effective or not. In the third cofinancing approach, budget holders use cost-effectiveness analysis to determine how much they would be willing to contribute towards the intervention, provided that other sectors are willing to pay for the remaining costs. In addition, we explore approaches for determining the HIV share in the cofinancing scenario., Results: We find that efficient structural interventions may be less likely to be prioritized, financed and taken to scale where sectors evaluate their options in isolation. A cofinancing approach minimizes welfare loss and could be incorporated in a sector budgeting perspective., Conclusion: Structural interventions may be underimplemented and their cross-sectoral benefits foregone. Cofinancing provides an opportunity for multiple HIV, health and development objectives to be achieved simultaneously, but will require effective cross-sectoral coordination mechanisms for planning, implementation and financing.

Background: High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay., Methods: In a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert., Findings: A triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort., Conclusions: A triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such.

Xpert MTB/RIF is a rapid test to diagnose tuberculosis (TB) and rifampicin-resistant TB. Cost and affordability will influence its uptake. We assessed the cost, globally and in 36 high-burden countries, of two strategies for diagnosing TB and multidrug-resistant (MDR)-TB: Xpert with follow-on diagnostics, and conventional diagnostics. Costs were compared with funding available for TB care and control, and donor investments in HIV prevention and care. Using Xpert to diagnose MDR-TB would cost US$70-90 million per year globally and be lower cost than conventional diagnostics globally and in all high-burden countries. Diagnosing TB in HIV-positive people using Xpert would also cost US$90-101 million per year and be lower cost than conventional diagnostics globally and in 33 out of 36 high-burden countries. Testing everyone with TB signs and symptoms would cost US$434-468 million per year globally, much more than conventional diagnostics. However, in European countries, Brazil and South Africa, the cost would represent <10% of TB funding. Introducing Xpert to diagnose MDR-TB and to diagnose TB in HIV-positive people is warranted in many countries. Using it to test everyone with TB signs and symptoms is affordable in several middle-income countries, but financial viability in low-income countries requires large increases in TB funding and/or further price reductions.

Objective: Estimate the potential impact of Avahan, the India AIDS Initiative, among female sex workers (FSWs) and their clients in five districts of Karnataka state, south India., Design: Examination of time trends in sexually transmitted infection (STI)/HIV prevalence from serial cross-sectional surveys, combined with mathematical modelling., Methods: Survey data from each district were used to monitor changes in FSW STI/HIV prevalence during Avahan. A deterministic model, parameterized with district-specific survey data, was used to simulate HIV/HSV-2/syphilis transmission among high-risk groups in each district. Latin hypercube sampling was used to obtain multiple parameter sets that reproduced district-specific HIV prevalence trends. A Bayesian framework tested whether self-reported increases in consistent condom use (CCU) during Avahan were more compatible with FSW HIV prevalence trends than assuming no or slow (preintervention rates) CCU increases, and were used to estimate HIV incidence and infections averted., Results: Declines in FSW HIV prevalence occurred over 5 years in all districts, and were statistically significant in three. Self-reported increases in CCU were more consistent with observed declines in HIV prevalence in three districts. In all five districts, an estimated 25-64% (32-70%) HIV infections were averted among FSWs (clients) over 5 years. This corresponded to 142-2092 FSW infections averted depending on the district (two-fold to nine-fold more among clients)., Conclusion: Empirical HIV prevalence trends combined with Bayesian modelling have provided plausible evidence that Avahan has reduced HIV transmission among FSWs and their clients. If current CCU levels are sustained, FSW HIV prevalence could decline to low levels by 2015, with many more infections averted.

Background: Cost-effectiveness studies inform resource allocation, strategy, and policy development. However, due to their complexity, dependence on assumptions made, and inherent uncertainty, synthesising, and generalising the results can be difficult. We assess cost-effectiveness models evaluating expected health gains and costs of HIV pre-exposure prophylaxis (PrEP) interventions., Methods and Findings: We conducted a systematic review comparing epidemiological and economic assumptions of cost-effectiveness studies using various modelling approaches. The following databases were searched (until January 2013): PubMed/Medline, ISI Web of Knowledge, Centre for Reviews and Dissemination databases, EconLIT, and region-specific databases. We included modelling studies reporting both cost and expected impact of a PrEP roll-out. We explored five issues: prioritisation strategies, adherence, behaviour change, toxicity, and resistance. Of 961 studies retrieved, 13 were included. Studies modelled populations (heterosexual couples, men who have sex with men, people who inject drugs) in generalised and concentrated epidemics from Southern Africa (including South Africa), Ukraine, USA, and Peru. PrEP was found to have the potential to be a cost-effective addition to HIV prevention programmes in specific settings. The extent of the impact of PrEP depended upon assumptions made concerning cost, epidemic context, programme coverage, prioritisation strategies, and individual-level adherence. Delivery of PrEP to key populations at highest risk of HIV exposure appears the most cost-effective strategy. Limitations of this review include the partial geographical coverage, our inability to perform a meta-analysis, and the paucity of information available exploring trade-offs between early treatment and PrEP., Conclusions: Our review identifies the main considerations to address in assessing cost-effectiveness analyses of a PrEP intervention--cost, epidemic context, individual adherence level, PrEP programme coverage, and prioritisation strategy. Cost-effectiveness studies indicating where resources can be applied for greatest impact are essential to guide resource allocation decisions; however, the results of such analyses must be considered within the context of the underlying assumptions made. Please see later in the article for the Editors' Summary.

Background: In sub-Saharan Africa (SSA) there are strong arguments for the provision of integrated sexual and reproductive health (SRH) and HIV services. Most HIV transmissions are sexually transmitted or associated with pregnancy, childbirth, and breastfeeding. Many of the behaviours that prevent HIV transmission also prevent sexually transmitted infections and unintended pregnancies. There is potential for integration to increase the coverage of HIV services, as individuals who use SRH services can benefit from HIV services and vice-versa, as well as increase cost-savings. However, there is a dearth of empirical evidence on effective models for integrating HIV/SRH services. The need for robust evidence led a consortium of three organizations - International Planned Parenthood Federation, Population Council and the London School of Hygiene & Tropical Medicine - to design/implement the Integra Initiative. Integra seeks to generate rigorous evidence on the feasibility, effectiveness, cost and impact of different models for delivering integrated HIV/SRH services in high and medium HIV prevalence settings in SSA., Methods/design: A quasi-experimental study will be conducted in government clinics in Kenya and Swaziland - assigned into intervention/comparison groups. Two models of service delivery are investigated: integrating HIV care/treatment into 1) family planning and 2) postnatal care. A full economic-costing will be used to assess the costs of different components of service provision, and the determinants of variations in unit costs across facilities/service models. Health facility assessments will be conducted at four time-periods to track changes in quality of care and utilization over time. A two-year cohort study of family planning/postnatal clients will assess the effect of integration on individual outcomes, including use of SRH services, HIV status (known/unknown) and pregnancy (planned/unintended). Household surveys within some of the study facilities' catchment areas will be conducted to profile users/non-users of integrated services and demand/receipt of integrated services, before-and-after the intervention. Qualitative research will be conducted to complement the quantitative component at different time points. Integra takes an embedded 'programme science' approach to maximize the uptake of findings into policy/practice., Discussion: Integra addresses existing evidence gaps in the integration evaluation literature, building on the limited evidence from SSA and the expertise of its research partners., Trial Registration: Current Controlled Trials NCT01694862.

Background: Approaches to HIV counselling and testing (HCT) within low-resource high HIV prevalence settings have shifted over the years from primarily client-initiated approaches to provider initiated. As part of an ongoing programme science research agenda, we examine the relative costs of provider-initiated testing and counselling (PITC) services compared with voluntary counselling and testing (VCT) services in the same health facilities in two low-resource settings: Kenya and Swaziland., Methods: Annual financial and economic costs and output measures were collected retrospectively from 28 health facilities. Total annual costs and average costs per client counselled and tested (C&T), and HIV-positive clients identified, were estimated., Results: VCT remains the predominant mode of HCT service delivery across both countries. However, unit cost per client C&T and per person testing HIV positive is lower for PITC than VCT across all facility types in Kenya, but the picture is mixed in Swaziland. Average cost per client C&T ranged from US $4.81 to US $6.11 in Kenya, US $6.92 to US $13.51 in Swaziland for PITC, and from US $5.05 to US $16.05 and US $8.68 to US $19.32 for VCT in Kenya and Swaziland, respectively., Conclusions: In the context of significant policy interest in optimising scarce HIV resources, this study demonstrates that there may be potential for substantial gains in efficiency in the provision of HCT services in both Kenya and Swaziland. However, considerations of how to deliver services efficiently need to be informed by local contextual factors, such as prevalence, service demand and availability of human resources.

Objectives: To review the literature on the potential efficiency gains of integrating HIV services with other health services., Design: Systematic literature review. Search of electronic databases, manual searching and snowball sampling. Studies that presented results on cost, efficiency or cost-effectiveness of integrated HIV services were included, focusing on low- and middle-income countries. Evidence was analysed and synthesised through a narrative approach and the quality of studies assessed., Results: Of 666 citations retrieved, 46 were included (35 peer reviewed and 11 from grey literature). A range of integrated HIV services were found to be cost-effective compared with 'do-nothing' alternatives, including HIV services integrated into sexual and reproductive health services, integrated tuberculosis/HIV services and HIV services integrated into primary healthcare. The cost of integrated HIV counselling and testing is likely to be lower than that of stand-alone counselling and testing provision; however, evidence is limited on the comparative costs of other services, particularly HIV care and treatment. There is also little known about the most efficient model of integration, the efficiency gain from integration beyond the service level and any economic benefit to HIV service users., Conclusions: In the context of increasing political commitment and previous reviews suggesting a strong public health argument for the integration of HIV services, the authors found the evidence on efficiency broadly supports further efforts to integrate HIV services. However, key evidence gaps remain, and there is an urgent need for further research in this area.

Background: The World Health Organization is currently developing guidelines on screening for tuberculosis disease to inform national screening strategies. This process is complicated by significant gaps in knowledge regarding mass screening. This study aimed to assess feasibility, uptake, yield, treatment outcomes, and costs of adding an active tuberculosis case-finding program to an existing mobile HIV testing service., Methods and Findings: The study was conducted at a mobile HIV testing service operating in deprived communities in Cape Town, South Africa. All HIV-negative individuals with symptoms suggestive of tuberculosis, and all HIV-positive individuals regardless of symptoms were eligible for participation and referred for sputum induction. Samples were examined by microscopy and culture. Active tuberculosis case finding was conducted on 181 days at 58 different sites. Of the 6,309 adults who accessed the mobile clinic, 1,385 were eligible and 1,130 (81.6%) were enrolled. The prevalence of smear-positive tuberculosis was 2.2% (95% CI 1.1-4.0), 3.3% (95% CI 1.4-6.4), and 0.4% (95% CI 1.4 015-6.4) in HIV-negative individuals, individuals newly diagnosed with HIV, and known HIV, respectively. The corresponding prevalence of culture-positive tuberculosis was 5.3% (95% CI 3.5-7.7), 7.4% (95% CI 4.5-11.5), 4.3% (95% CI 2.3-7.4), respectively. Of the 56 new tuberculosis cases detected, 42 started tuberculosis treatment and 34 (81.0%) completed treatment. The cost of the intervention was US$1,117 per tuberculosis case detected and US$2,458 per tuberculosis case cured. The generalisability of the study is limited to similar settings with comparable levels of deprivation and TB and HIV prevalence., Conclusions: Mobile active tuberculosis case finding in deprived populations with a high burden of HIV and tuberculosis is feasible, has a high uptake, yield, and treatment success. Further work is now required to examine cost-effectiveness and affordability and whether and how the same results may be achieved at scale.

Background: Avahan, the India AIDS Initiative, delivers HIV prevention services to high-risk populations at scale. Although the broad costs of such HIV interventions are known, to-date there has been little data available on the comparative costs of reaching different target groups, including female sex workers (FSWs), replace with 'high risk men who have sex with men (HR-MSM) and trans-genders., Methods: Costs are estimated for the first three years of Avahan scale up differentiated by typology of female sex workers (brothel, street, home, lodge based, bar based), HR-MSM and transgenders in urban districts in India: Mumbai and Thane in Maharashtra and Bangalore in Karnataka. Financial and economic costs were collected prospectively from a provider perspective. Outputs were measured using data collected by the Avahan programme. Costs are presented in US$2008., Results: Costs were found to vary substantially by target group. Non-governmental organisations (NGOs) working with transgender populations had a higher mean cost (US $116) per person reached compared to those dealing primarily with FSWs (US $75-96) and MSWs (US $90) by the end of year three of the programme in Mumbai. The mean cost of delivering the intervention to HR-MSMs (US $42) was higher than delivering it to FSWs (US $37) in Bangalore. The package of services delivered to each target group was similar, and our results suggest that cost variation is related to the target population size, the intensity of the programme (in terms of number of contacts made per year) and a number of specific issues related to each target group., Conclusions: Based on our data policy makers and program managers need to consider the ease of accessing high risk population when planning and budgeting for HIV prevention services for these populations and avoid funding programmes on the basis of target population size alone.

Background: Xpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings., Methods and Findings: We estimate the impact of the introduction of Xpert on the costs and cost-effectiveness of TB care using decision analytic modelling, comparing the introduction of Xpert to a base case of smear microscopy and clinical diagnosis in India, South Africa, and Uganda. The introduction of Xpert increases TB case finding in all three settings; from 72%-85% to 95%-99% of the cohort of individuals with suspected TB, compared to the base case. Diagnostic costs (including the costs of testing all individuals with suspected TB) also increase: from US$28-US$49 to US$133-US$146 and US$137-US$151 per TB case detected when Xpert is used "in addition to" and "as a replacement of" smear microscopy, respectively. The incremental cost effectiveness ratios (ICERs) for using Xpert "in addition to" smear microscopy, compared to the base case, range from US$41-$110 per disability adjusted life year (DALY) averted. Likewise the ICERS for using Xpert "as a replacement of" smear microscopy range from US$52-$138 per DALY averted. These ICERs are below the World Health Organization (WHO) willingness to pay threshold., Conclusions: Our results suggest that Xpert is a cost-effective method of TB diagnosis, compared to a base case of smear microscopy and clinical diagnosis of smear-negative TB in low- and middle-income settings where, with its ability to substantially increase case finding, it has important potential for improving TB diagnosis and control. The extent of cost-effectiveness gain to TB programmes from deploying Xpert is primarily dependent on current TB diagnostic practices. Further work is required during scale-up to validate these findings.

In most developed countries, HCV is primarily transmitted by injecting drug users (IDUs). HCV antiviral treatment is effective, and deemed cost-effective for those with no re-infection risk. However, few active IDUs are currently treated. Previous modelling studies have shown antiviral treatment for active IDUs could reduce HCV prevalence, and there is emerging interest in developing targeted IDU treatment programmes. However, the optimal timing and scale-up of treatment is unknown, given the real-world constraints commonly existing for health programmes. We explore how the optimal programme is affected by a variety of policy objectives, budget constraints, and prevalence settings. We develop a model of HCV transmission and treatment amongst active IDUs, determine the optimal treatment programme strategy over 10 years for two baseline chronic HCV prevalence scenarios (30% and 45%), a range of maximum annual budgets (£50,000-300,000 per 1,000 IDUs), and a variety of objectives: minimising health service costs and health utility losses; minimising prevalence at 10 years; minimising health service costs and health utility losses with a final time prevalence target; minimising health service costs with a final time prevalence target but neglecting health utility losses. The largest programme allowed for a given budget is the programme which minimises both prevalence at 10 years, and HCV health utility loss and heath service costs, with higher budgets resulting in greater cost-effectiveness (measured by cost per QALY gained compared to no treatment). However, if the objective is to achieve a 20% relative prevalence reduction at 10 years, while minimising both health service costs and losses in health utility, the optimal treatment strategy is an immediate expansion of coverage over 5-8 years, and is less cost-effective. By contrast, if the objective is only to minimise costs to the health service while attaining the 20% prevalence reduction, the programme is deferred until the final years of the decade, and is the least cost-effective of the scenarios.

Background: Resistance to commonly used antituberculosis drugs is emerging worldwide. Conventional drug-susceptibility testing (DST) methods are slow and demanding. Alternative, rapid DST methods would permit the early detection of drug resistance and, in turn, arrest tuberculosis transmission., Methods: A cost-effectiveness analysis of 5 DST methods was performed in the context of a clinical trial that compared rapid with conventional DST methods. The methods under investigation were direct phage-replication assay (FASTPlaque-Response; Biotech), direct amplification and reverse hybridization of the rpoB gene (INNO-LiPA; Innogenetics), indirect colorimetric minimum inhibitory concentration assay (MTT; ICN Biomedicals), and direct proportion method on Löwenstein-Jensen medium. These were compared with the widely used indirect proportion method on Löwenstein-Jensen medium., Results: All alternative DST methods were found to be cost-effective, compared with other health care interventions. DST methods also generate substantial cost savings in settings of high prevalence of multidrug-resistant tuberculosis. Excluding the effects of transmission, the direct proportion method on Löwenstein-Jensen medium was the most cost-effective alternative DST method for patient groups with prevalences of multidrug-resistant tuberculosis of 2%, 5%, 20%, and 50% (cost in US$2004, $94, $36, $8, and $2 per disability-adjusted life year, respectively)., Conclusion: Alternative, rapid methods for DST are cost-effective and should be considered for use by national tuberculosis programs in middle-income countries.

Considerable effort has been made to estimate the global resource requirements of scaling-up HIV/AIDS and tuberculosis (TB) interventions. There are currently several medium- and long-term global estimates available. Comprehensive country specific estimates are now urgently needed to ensure the successful scaling-up of these services. This paper reviews evidence on the global resource requirements of scaling-up HIV/AIDS and TB interventions. The purpose of this review is to summarise and critically appraise the methods used in the global estimates and to identify remaining knowledge gaps, particularly those relevant to country level estimation. This review found that the estimates of global resource requirements provide sound methodological guidance for countries on the basic steps to follow. However, there are still many areas that require further development or evidence. These include the following. Firstly, the methods used to assess the capacity to scale up HIV/AIDS and TB services need to be further refined. In particular countries need simple methods to assess human resource capacity. Secondly, investments need to be made to improve country level data on the costs and effectiveness of HIV/AIDS and TB services. In particular efforts should be focused on producing standardised unit costs for each intervention by country, which reflect the reality of domestic resource use. Thirdly, simple costing models, which appropriately integrate systems costs need to be developed for use at the country level. Finally, resources needs estimation needs to be embedded by countries in multi-sectoral expenditure planning processes. Countries and global agencies will continue to need estimates for different purposes at different times. Therefore attention should move away from specific estimates, to the longer term aim of building capacity at the country level, supported by global agencies. This will be of mutual benefit. Those making national resource estimates can learn from the experience of global estimation. Concurrently, global resource estimates can build on the evidence emerging from improved national resource estimates.