Cost and cost-effectiveness of a universal HIV testing and treatment intervention in Zambia and South Africa: evidence and projections from the HPTN 071 (PopART) trial

Background: The HPTN 071 (PopART) trial showed that a combination HIV prevention package including universal HIV testing and treatment (UTT) reduced population-level incidence of HIV compared with standard care. However, evidence is scarce on the costs and cost-effectiveness of such an intervention. Methods: Using an individual-based model, we simulated the PopART intervention and standard care with antiretroviral therapy (ART) provided according to national guidelines for the 21 trial communities in Zambia and South Africa (for all individuals aged >14 years), with model parameters and primary cost data collected during the PopART trial and from published sources. Two intervention scenarios were modelled: annual rounds of PopART from 2014 to 2030 (PopART 2014–30; as the UNAIDS Fast-Track target year) and three rounds of PopART throughout the trial intervention period (PopART 2014–17). For each country, we calculated incremental cost-effectiveness ratios (ICERs) as the cost per disability-adjusted life-year (DALY) and cost per HIV infection averted. Cost-effectiveness acceptability curves were used to indicate the probability of PopART being cost-effective compared with standard care at different thresholds of cost per DALY averted. We also assessed budget impact by projecting undiscounted costs of the intervention compared with standard care up to 2030. Findings: During 2014–17, the mean cost per person per year of delivering home-based HIV counselling and testing, linkage to care, promotion of ART adherence, and voluntary medical male circumcision via community HIV care providers for the simulated population was US$6·53 (SD 0·29) in Zambia and US$7·93 (0·16) in South Africa. In the PopART 2014–30 scenario, median ICERs for PopART delivered annually until 2030 were $2111 (95$3248 (2472–3963) per HIV infection averted in South Africa; and $593 (95$645 (538–757) per DALY averted in South Africa. In the PopART 2014–17 scenario, PopART averted one infection at a cost of $1318 (1098–1591) in Zambia and$2236 (1601–2916) in South Africa, and averted one DALY at $258 (225–298) in Zambia and$326 (266–391) in South Africa, when outcomes were projected until 2030. The intervention had almost 100% probability of being cost-effective at thresholds greater than $700 per DALY averted in Zambia, and greater than$800 per DALY averted in South Africa, in the PopART 2014–30 scenario. Incremental programme costs for annual rounds until 2030 were $46·12 million (for a mean of 341 323 people) in Zambia and$30·24 million (for a mean of 165 852 people) in South Africa. Interpretation: Combination prevention with universal home-based testing can be delivered at low annual cost per person but accumulates to a considerable amount when scaled for a growing population. Combination prevention including UTT is cost-effective at thresholds greater than $800 per DALY averted and can be an efficient strategy to reduce HIV incidence in high-prevalence settings. Funding: US National Institutes of Health, President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, Bill & Melinda Gates Foundation

Identity and Mobility: Historical Fractionalization, Parochial Institutions, and Occupational Choice in the American Midwest

This paper examines the role played by a specific identity, defined as the attachment to a hometown, in determining occupational choice and mobility. The analysis links competition between ethnic networks in the Midwest when it was first developing, and the in-group identity that emerged endogenously to support these networks, to institutional participation and occupational choice today. Individuals born in counties with greater ethnic fractionalization in 1860 are today -- 150 years later --(i) significantly more likely to participate in institutions such as churches and parochial schools that transmit identity from one generation to the next, and (ii) significantly less likely to select into mobile skilled occupations. The effect of historical fractionalization on participation in these socializing institutions actually grows stronger over the course of the twentieth century, emphasizing the idea that small differences in initial conditions can have large long-term effects on institutions and economic choices.Identity, Institutional persistence, Networks, Occupational choice, Mobil- ity

Transmission reduction, health benefits, and upper-bound costs of interventions to improve retention on antiretroviral therapy: a combined analysis of three mathematical models

BACKGROUND: In this so-called treat-all era, antiretroviral therapy (ART) interruptions contribute to an increasing proportion of HIV infections and deaths. Many strategies to improve retention on ART cost more than standard of care. In this study, we aimed to estimate the upper-bound costs at which such interventions should be adopted. METHODS: In this combined analysis, we compared the infections averted, disability-adjusted life-years (DALYs) averted, and upper-bound costs of interventions that improve ART retention in three HIV models with diverse structures, assumptions, and baseline settings: EMOD in South Africa, Optima in Malawi, and Synthesis in sub-Saharan African low-income and middle-income countries (LMICs). We modelled estimates over a 40-year time horizon, from a baseline of Jan 1, 2022, when interventions would be implemented, to Jan 1, 2062. We varied increment of ART retention (25%, 50%, 75%, and 100% retention), the extent to which interventions could be targeted towards individuals at risk of interrupting ART, and cost-effectiveness thresholds in each setting. FINDINGS: Despite simulating different settings and epidemic trends, all three models produced consistent estimates of health benefit (ie, DALYs averted) and transmission reduction per increment in retention. The range of estimates was 1·35-3·55 DALYs and 0·12-0·20 infections averted over the 40-year time horizon per additional person-year retained on ART. Upper-bound costs varied by setting and intervention effectiveness. Improving retention by 25% among all people receiving ART, regardless of risk of ART interruption, gave an upper-bound cost per person-year of US$2-6 in Optima (Malawi),$43-68 in Synthesis (LMICs in sub-Saharan Africa), and $28-180 in EMOD (South Africa). A maximally targeted and effective retention intervention had an upper-bound cost per person-year of US$93-223 in Optima (Malawi), $871-1389 in Synthesis (LMICs in sub-Saharan Africa), and$1013-6518 in EMOD (South Africa). INTERPRETATION: Upper-bound costs that could improve ART retention vary across sub-Saharan African settings and are likely to be similar to or higher than was estimated before the start of the treat-all era. Upper-bound costs could be increased by targeting interventions to those most at risk of interrupting ART. FUNDING: Bill & Melinda Gates Foundation

The cost and cost-effectiveness of alternative strategies to expand treatment to HIV-positive South Africans: scale economies and outreach costs

This repository item contains a single issue of the Health and Development Discussion Papers, an informal working paper series that began publishing in 2002 by the Boston University Center for Global Health and Development. It is intended to help the Center and individual authors to disseminate work that is being prepared for journal publication or that is not appropriate for journal publication but might still have value to readers.The South African government is currently discussing various alternative approaches to the further expansion of antiretroviral treatment (ART) in public-sector facilities. We used the EMOD-HIV model, a HIV transmission model which projects South African HIV incidence and prevalence and ARV treatment by age-group for alternative combinations of treatment eligibility criteria and testing, to generate 12 epidemiological scenarios. Using data from our own bottom-up cost analyses in South Africa, we separate outpatient cost into nonscale- dependent costs (drugs and laboratory tests) and scale-dependent cost (staff, space, equipment and overheads) and model the cost of production according to the expected future number and size of clinics. On the demand side, we include the cost of creating and sustaining the projected incremental demand for testing and treatment. Previous research with EMOD-HIV has shown that more vigorous recruitment of patients with CD4 counts less than 350 is an advantageous policy over a five-year horizon. Over 20 years, however, the model assumption that a person on treatment is 92% less infectious improves the cost-effectiveness of higher eligibility thresholds, averting HIV infections for between $1,700 and$2,800, while more vigorous expansion under the current guidelines would cost more than $7,500 per incremental HIV infection averted. Based on analysis of the sensitivity of the results to 1,728 alternative parameter combinations at each of four discount rates, we conclude that better knowledge of the behavioral elasticities could reduce the uncertainty of cost estimates by a factor of 4 to 10

Potential Impact of Antiretroviral Chemoprophylaxis on HIV-1 Transmission in Resource-Limited Settings

Background. The potential impact of pre-exposure chemoprophylaxis (PrEP) an heterosexual transmission of HIV-1 infection in resource-limited settings is uncertain. Methodology/Principle Findings. A deterministic mathematical model was used to simulate the effects of antiretroval PreP on an HIV-1 epidemic in sub-Saharan Africa under different scenarios (optimistic neutral and pessimistic) both with and without sexual disinhibition. Sensitivity analyses were used to evaluate the effect of uncertainty in input parameters on model output and included calculation of partial rank correlations and standardized rank regressions. In the scenario without sexual disinhibition after PrEP initiation, key parameters influencing infections prevented were effectiveness of PrEP (partial rank correlation coefficient (PRCC) = 0.94), PrEP discontinuation rate (PRCC=-0.94), level of coverage (PRCC=0.92), and time to achieve target coverage (PRCC=-082). In the scenario with sexual disinhibition, PrEP effectiveness and the extent of sexual disinhibition had the greatest impact on prevention. An optimistic scenario of PrEP with 90% effectiveness and 75% coverage of the general population predicted a 74% decline in cumulative HIV-1 infections after 10 years, and a 28.8% decline with PrEP targeted to the highest risk groups (16% of the population). Even With a 100% increase in at-risk behavior from sexual disinhibition, a beneficial effect (23.4%-62.7% decrease in infections) was seen with 90% effective PrEP across a broad range of coverage (25%-75%). Similar disinhibition led to a rise in infections with lower effectiveness of PrEP (≤50%). Conclusions/Significance. Mathematical modeling supports the potential public health benefit of PrEP. Approximately 2.7 to 3.2 million new HIV-1 infections could be averaged in southern sub-Saharan Africa over 10 years by targeting PrEP (having 90% effectiveness) to those at highest behavioral risk and by preventing sexual disinhibition. This benefit could be lost, however, by sexual disinhibition and by high PrEP discontinuation, especially with lower PrEP effectiveness (≤:50%). © 2007 Abbas et al

Aiming for Utility in ‘Systems?based Evaluation’: A Research?based Framework for Practitioners

System dynamics modelling (SDM) was used and process researched as a case to investigate its utility as a systems?based evaluation (SBE) approach. A system dynamics (SD) model was developed to evaluate the potential requirements and implications on the health systems of the ambitious antiretroviral therapy (ART) scale?up strategy in Lusaka, Zambia. Research on SDM for strategic evaluation provided insights and principles for future application of SBE. The SD diagrams readily inspired new insights while practical constraints limited use of the model for action planning. Research suggests that utility of SBE begins with engaging stakeholders to share and align their views on a representation of the system and progresses to their reinterpretations of the system that they inhabit, ultimately moving towards transformative change. Evaluators must balance two purposes in managing for utility of SBE approaches: producing a defensible representation of the system(s) and facilitating transformative change appropriately with and for system stakeholders

Modelling the South African tuberculosis epidemic: the effect of HIV, sex differences, and the impact of interventions

The South African tuberculosis (TB) epidemic is driven mainly by HIV, and the TB disease burden is greater in males than females. Additional factors that drive the epidemic include undiagnosed and untreated TB, contributing to transmission; and highly prevalent TB risk factors such as alcohol misuse, smoking, diabetes, and undernutrition, which increase the risk of progression to TB disease. These factors are distributed differently by sex and likely explain the observed sex disparities in TB. The South African TB control programme has implemented multiple interventions, including directly observed therapy strategy (DOTS), antiretroviral therapy (ART), intensified screening activities, the provision of isoniazid preventative therapy (IPT) and the implementation of Xpert MTB/RIF as a first-line diagnostic tool. However, few analyses have quantified the historical impact of HIV and the combined impact of TB interventions on the South African TB epidemic at a national level. In addition, factors that influence sex disparities in the South African TB burden have not been explored thoroughly. Also, it remains uncertain whether, with existing interventions, it would be feasible for South Africa to meet the End TB targets to reduce TB incidence and mortality by 80% and 90% respectively (relative to 2015 levels) by 2030. This thesis aims to address the abovementioned gaps in knowledge and provide insights into understanding the population-level TB dynamics, using a mathematical model. The first objective is to quantify TB incidence and mortality due to HIV and assess the impact of interventions mentioned above on TB incidence and mortality between 1990 and 2019. The second objective is to explore the extent to which the following factors contribute to sex differences in TB: HIV, ART uptake, smoking, alcohol abuse, undernutrition, diabetes, health-seeking patterns, social contact rates and TB treatment discontinuation. The third objective is to project the future impact of increasing screening, improving linkage to TB care and retention, increasing preventative therapy, and reducing ART interruptions. An age- and sex-stratified dynamic tuberculosis transmission model for South Africa was developed. To dynamically model the effect of HIV and ART on TB incidence and mortality, the TB model was integrated into the Thembisa model, a previously developed HIV and demographic model. In addition, age- and sex-specific relative risks were applied to rates of progression to TB disease to capture age and sex differences in tuberculosis incidence. The model also included a diagnostic pathway representing health-seeking patterns and the sensitivity and specificity of the diagnostic algorithm. A Bayesian approach was used to calibrate the model to the numbers of people starting treatment from the electronic tuberculosis register, deaths from the vital register, microbiological tests, and the national tuberculosis prevalence survey. The model estimated rapid increases in TB incidence and mortality in the mid-to-late 1990s, influenced by HIV. Between 1990 and 2019, approximately eight million people developed tuberculosis, and two million died from TB; HIV accounted for at least half and two-thirds of the TB incidence and mortality, respectively. The TB epidemic peaked in the mid-to-late 2000s, followed by declines until 2019. The ART program and TB screening efforts, which were expanded in the mid-2000s, contributed the most to reductions in TB incidence and mortality, while other interventions had minor impacts. Due to the heavier HIV burden in women than men, women experienced greater HIV-associated TB incidence and mortality than men. However, because of the higher ART uptake among women than men, women experienced greater relative reductions in TB incidence and mortality over the period 2005– 2019. Consequently, the higher TB burden among men has been sustained; the estimated male-to-female ratios of TB incidence and mortality in 2019 were 1.7 and 1.65, respectively. Additional factors explaining the excess TB in men are smoking, alcohol abuse and delays in health-seeking patterns. Sex differences in undernutrition, social contact patterns, and treatment discontinuation had minimal effect on TB sex disparities. Projections of the model to 2030, considering the effects of COVID-19-related disruptions to TB care, suggest that increasing TB screening would be the most impactful among all interventions explored. However, the model also suggests that the 2030 End TB milestone is unlikely to be met by scaling up existing interventions. Other interventions that need to be explored include targeted universal TB testing and other diagnostic tests such as digital chest x-rays, urine Lipoarabinomannan, and biomarkers to identify individuals at risk of TB disease. Accelerating progress toward TB incidence and mortality reductions will require developing affordable and efficient rapid diagnostic tools to identify potential and active TB cases. Research and innovation efforts towards finding a vaccine effective in preventing TB disease are also critical. In addition, it is essential to improve the uptake of TB preventative therapy in HIV-positive individuals and perhaps further expand provision to other TB risk group