Know your HIV epidemic (KYE) report: review of the HIV epidemic in South Africa.

In order to update and consolidate South Africa’s evidence base for HIV-prevention interventions, it was decided by the Government of South Africa to commission a synthesis of the available data on the epidemiology of prevalent and incident HIV infections, and the wider epidemic context of these infections. This know your epidemic (KYE) approach has been successfully implemented in a number of sub-Saharan African countries.2 The process involves a desk review and secondary analysis of existing biological, behavioural and socio-demographic data in order to determine the epidemiology of new HIV infections. KYE reports present key findings and policy and programme recommendations which are grounded in local evidence and aim to support decision-making and improve HIV-prevention results. In 2010, South Africa also conducted a know your response (KYR) review, which critically assessed HIV-prevention policies, programmes and resource allocations. The overall results of this HIV epidemic review and the KYR review will be published in a separate, national KYE/KYR synthesis report

Cash transfers to enhance TB control: lessons from the HIV response

Background: The World Health Organization prioritises a more holistic global response to end the tuberculosis (TB) epidemic by 2030. Based on experiences in the HIV response, social protection, and in particular cash transfers, show promise for contributing to this. Currently, individual-level evidence for the potential of cash transfers to prevent TB by addressing the structural social determinants of disease is lacking. To identify priority actions for the TB research agenda, we appraised efforts by the HIV response to establish the role of cash transfers in preventing HIV infection. Main body The HIV response has evaluated the effects of cash transfers on risky sexual behaviours and HIV incidence. Work has also evaluated the added effects of supplementing cash transfers with psychosocial support. The HIV response has focused research on populations with disproportionate HIV risk, and used a mix of explanatory evaluations, which use ideal conditions, and pragmatic evaluations, which use operational conditions, to generate evidence that is both causally valid and applicable to the real world. It has always collaborated with multiple stakeholders in funding and evaluating projects. Learning from the HIV response, priority actions for the TB response should be to investigate the effect of cash transfers on intermediary social determinants of active TB disease, and TB incidence, as well as the added effects of supplementing cash transfers with psychosocial support. Work should be focused on key groups in high burden settings, and look to build a combination of explanatory and pragmatic evidence to inform policy decisions in this field. To achieve this, there is an urgent need to facilitate collaborations between groups interested in evaluating the impact of cash transfers on TB risk. Conclusions The HIV response highlights several priority actions necessary for the TB response to establish the potential of cash transfers to prevent TB by addresing the structural social determinants of disease

Public health benefits of shifting from inpatient to outpatient TB care in Eastern Europe: optimising TB investments in Belarus, the Republic of Moldova, and Romania

Background: High rates of drug-resistant tuberculosis (DR TB) continue to threaten public health, especially in Eastern Europe. Costs for treating DR TB are substantially higher than treating drug-susceptible TB, and higher yet if DR TB services are delivered in hospital. Therefore, countries are encouraged to transition from inpatient to ambulatory-focused TB care, which has been shown to have non-inferior health outcomes. / Methods: Allocative efficiency analyses were conducted for three countries in Eastern Europe, Belarus, the Republic of Moldova, and Romania to minimise a combination of active TB cases, prevalence of active TB, and TB-related deaths by 2035. These mathematical optimisations were carried out using Optima TB, a dynamical compartmental model of TB transmission. The focus of this study was to project the health and financial gains that could be realised if TB service delivery shifted from hospital to ambulatory-based care. / Findings: These analyses show that transitioning from inpatient to ambulatory TB care could reduce treatment costs by 5%−31% or almost 35 million US dollars across these three countries without affecting the quality of care. Improved TB outcomes could be achieved without additional spending by reinvesting these potential savings in cost-effective prevention and diagnosis interventions. / Conclusions: National governments should examine barriers delaying the adoption of outpatient DR TB care and consider the lost opportunities caused by delays in switching to more efficient and effective treatment modes

Public health benefits of shifting from hospital-focused to ambulatory TB care in Eastern Europe: Optimising TB investments in Belarus, the Republic of Moldova, and Romania

High rates of drug-resistant tuberculosis (DR-TB) continue to threaten public health, especially in Eastern Europe. Costs for treating DR-TB are substantially higher than treating drug-susceptible TB, and higher yet if DR-TB services are delivered in hospital. The WHO recommends that multidrug-resistant (MDR) TB be treated using mainly ambulatory care, shown to have non-inferior health outcomes, however, there has been a delay to transition away from hospital-focused MDR-TB care in certain Eastern European countries. Allocative efficiency analyses were conducted for three countries in Eastern Europe, Belarus, the Republic of Moldova, and Romania, to minimise a combination of TB incidence, prevalence, and mortality by 2035. A primary focus of these studies was to determine the health benefits and financial savings that could be realised if DR-TB service delivery shifted from hospital-focused to ambulatory care. Here we provide a comprehensive assessment of findings from these studies to demonstrate the collective benefit of transitioning from hospital-focused to ambulatory TB care, and to address common regional considerations. We highlight that transitioning from hospital-focused to ambulatory TB care could reduce treatment costs by 20% in Romania, 24% in Moldova, and by as much as 40% in Belarus or almost 35 million US dollars across these three countries by 2035 without affecting quality of care. Improved TB outcomes could be achieved, however, without additional spending by reinvesting these savings in higher-impact TB diagnosis and more efficacious DR-TB treatment regimens. We found commonalities in the large portion of TB cases treated in hospital across these three regional countries, and similar obstacles to transitioning to ambulatory care. National governments in the Eastern European region should examine barriers delaying adoption of ambulatory DR-TB care and consider lost opportunities caused by delays in switching to more efficient treatment modes

How should HIV resources be allocated? Lessons learnt from applying Optima HIV in 23 countries.

INTRODUCTION: With limited funds available, meeting global health targets requires countries to both mobilize and prioritize their health spending. Within this context, countries have recognized the importance of allocating funds for HIV as efficiently as possible to maximize impact. Over the past six years, the governments of 23 countries in Africa, Asia, Eastern Europe and Latin America have used the Optima HIV tool to estimate the optimal allocation of HIV resources. METHODS: Each study commenced with a request by the national government for technical assistance in conducting an HIV allocative efficiency study using Optima HIV. Each study team validated the required data, calibrated the Optima HIV epidemic model to produce HIV epidemic projections, agreed on cost functions for interventions, and used the model to calculate the optimal allocation of available funds to best address national strategic plan targets. From a review and analysis of these 23 country studies, we extract common themes around the optimal allocation of HIV funding in different epidemiological contexts. RESULTS AND DISCUSSION: The optimal distribution of HIV resources depends on the amount of funding available and the characteristics of each country's epidemic, response and targets. Universally, the modelling results indicated that scaling up treatment coverage is an efficient use of resources. There is scope for efficiency gains by targeting the HIV response towards the populations and geographical regions where HIV incidence is highest. Across a range of countries, the model results indicate that a more efficient allocation of HIV resources could reduce cumulative new HIV infections by an average of 18% over the years to 2020 and 25% over the years to 2030, along with an approximately 25% reduction in deaths for both timelines. However, in most countries this would still not be sufficient to meet the targets of the national strategic plan, with modelling results indicating that budget increases of up to 185% would be required. CONCLUSIONS: Greater epidemiological impact would be possible through better targeting of existing resources, but additional resources would still be required to meet targets. Allocative efficiency models have proven valuable in improving the HIV planning and budgeting process

Optima TB: A tool to help optimally allocate tuberculosis spending

Approximately 85% of tuberculosis (TB) related deaths occur in low- and middle-income countries where health resources are scarce. Effective priority setting is required to maximise the impact of limited budgets. The Optima TB tool has been developed to support analytical capacity and inform evidence-based priority setting processes for TB health benefits package design. This paper outlines the Optima TB framework and how it was applied in Belarus, an upper-middle income country in Eastern Europe with a relatively high burden of TB. Optima TB is a population-based disease transmission model, with programmatic cost functions and an optimisation algorithm. Modelled populations include age-differentiated general populations and higher-risk populations such as people living with HIV. Populations and prospective interventions are defined in consultation with local stakeholders. In partnership with the latter, demographic, epidemiological, programmatic, as well as cost and spending data for these populations and interventions are then collated. An optimisation analysis of TB spending was conducted in Belarus, using program objectives and constraints defined in collaboration with local stakeholders, which included experts, decision makers, funders and organisations involved in service delivery, support and technical assistance. These analyses show that it is possible to improve health impact by redistributing current TB spending in Belarus. Specifically, shifting funding from inpatient- to outpatient-focused care models, and from mass screening to active case finding strategies, could reduce TB prevalence and mortality by up to 45% and 50%, respectively, by 2035. In addition, an optimised allocation of TB spending could lead to a reduction in drug-resistant TB infections by 40% over this period. This would support progress towards national TB targets without additional financial resources. The case study in Belarus demonstrates how reallocations of spending across existing and new interventions could have a substantial impact on TB outcomes. This highlights the potential for Optima TB and similar modelling tools to support evidence-based priority setting

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Effectiveness of and Financial Returns to Voluntary Medical Male Circumcision for HIV Prevention in South Africa: An Incremental Cost-Effectiveness Analysis

<div><p>Background</p><p>Empirical studies and population-level policy simulations show the importance of voluntary medical male circumcision (VMMC) in generalized epidemics. This paper complements available scenario-based studies (projecting costs and outcomes over some policy period, typically spanning decades) by adopting an incremental approach—analyzing the expected consequences of circumcising one male individual with specific characteristics in a specific year. This approach yields more precise estimates of VMMC’s cost-effectiveness and identifies the outcomes of current investments in VMMC (e.g., within a fiscal budget period) rather than of investments spread over the entire policy period.</p><p>Methods/Findings</p><p>The model has three components. We adapted the ASSA2008 model, a demographic and epidemiological model of the HIV epidemic in South Africa, to analyze the impact of one VMMC on HIV incidence over time and across the population. A costing module tracked the costs of VMMC and the resulting financial savings owing to reduced HIV incidence over time. Then, we used several financial indicators to assess the cost-effectiveness of and financial return on investments in VMMC. One circumcision of a young man up to age 20 prevents on average over 0.2 HIV infections, but this effect declines steeply with age, e.g., to 0.08 by age 30. Net financial savings from one VMMC at age 20 are estimated at US$617 at a discount rate of 5% and are lower for circumcisions both at younger ages (because the savings occur later and are discounted more) and at older ages (because male circumcision becomes less effective). Investments in male circumcision carry a financial rate of return of up to 14.5% (for circumcisions at age 20). The cost of a male circumcision is refinanced fastest, after 13 y, for circumcisions at ages 20 to 25. Principal limitations of the analysis arise from the long time (decades) over which the effects of VMMC unfold—the results are therefore sensitive to the discount rate applied, and more generally to the future course of the epidemic and of HIV/AIDS-related policies pursued by the government.</p><p>Conclusions</p><p>VMMC in South Africa is highly effective in reducing both HIV incidence and the financial costs of the HIV response. The return on investment is highest if males are circumcised between ages 20 and 25, but this return on investment declines steeply with age.</p></div

Net savings from one male circumcision, by discount rate (USD, adjusted for inflation).

<p>Net savings from one male circumcision, by discount rate (USD, adjusted for inflation).</p