A Model-Based Cost-Effectiveness Analysis of Long-Acting Monoclonal Antibody (Tixagevimab and Cilgavimab: Evusheld) Preventive Treatment for High-Risk Populations Against SARS-CoV-2 in Korea.

BACKGROUND: Tixagevimab and cilgavimab (Evusheld) administration is a recommended strategy for unvaccinated patients with immunocompromised conditions and severe allergic reaction conditions to protect high-risk individuals and control the coronavirus disease 2019 (COVID-19) epidemic. We estimated the cost-effectiveness of Evusheld in key risk populations: 1) immunocompromised (vaccinated/unvaccinated), 2) severe allergic reaction, and 3) unvaccinated elderly high-risk groups. METHODS: Based on the estimated target risk group population, we used a model of COVID-19 transmission to estimate the size of the risk group population for whom Evusheld treatment may help prevent symptomatic COVID-19 (and deaths) in 2022. We projected Evusheld intervention costs, quality-adjusted life year (QALY) lost, cost averted and QALY gained by reduced COVID-19 incidence, and incremental cost-effectiveness (cost per QALY gained) in each modeled population from the healthcare system perspective. RESULTS: Our study demonstrated that Evusheld treatment for COVID-19 infection in South Korea is highly cost-effective for unvaccinated risk groups ($18,959 per QALY gained for immunocompromised and $23,978 per QALY gained for high-risk elderly groups) and moderately cost-effective among individuals who are vaccinated immunocompromised ($46,494 per QALY gained), or have severe allergic reactions ($45,996 per QALY gained). Evusheld's cost-effectiveness may be subject to risk-group-specific COVID-19 disease progression and Evusheld efficacy and cost, which may change in future epidemic scenarios. CONCLUSION: As the COVID-19 variants and risk group-specific durable efficacy, toxicity (and/or resistance) and optimal dosing of Evusheld remain uncertain, better empirical estimates to inform these values in different epidemiological contexts are needed. These results may help decision-makers prioritize resources toward more equitable and effective COVID-19 control efforts.

Attrition from HIV treatment after enrollment in a differentiated service delivery model: A cohort analysis of routine care in Zambia.

BACKGROUND: Many sub-Saharan Africa countries are scaling up differentiated service delivery (DSD) models for HIV treatment to increase access and remove barriers to care. We assessed factors associated with attrition after DSD model enrollment in Zambia, focusing on patient-level characteristics. METHODS: We conducted a retrospective record review using electronic medical records (EMR) of adults (≥15 years) initiated on antiretroviral (ART) between 01 January 2018 and 30 November 2021. Attrition was defined as lost to follow-up (LTFU) or died by November 30, 2021. We categorized DSD models into eight groups: fast-track, adherence groups, community pick-up points, home ART delivery, extended facility hours, facility multi-month dispensing (MMD, 4-6-month ART dispensing), frequent refill care (facility 1-2 month dispensing), and conventional care (facility 3 month dispensing, reference group). We used Fine and Gray competing risk regression to assess patient-level factors associated with attrition, stratified by sex and rural/urban setting. RESULTS: Of 547,281 eligible patients, 68% (n = 372,409) enrolled in DSD models, most commonly facility MMD (n = 306,430, 82%), frequent refill care (n = 47,142, 13%), and fast track (n = 14,433, 4%), with <2% enrolled in the other DSD groups. Retention was higher in nearly all DSD models for all dispensing intervals, compared to the reference group, except fast track for the ≤2 month dispensing group. Retention benefits were greatest for patients in the extended clinic hours group and least for fast track dispensing. CONCLUSION: Although retention in HIV treatment differed by DSD type, dispensing interval, and patient characteristics, nearly all DSD models out-performed conventional care. Understanding the factors that influence the retention of patients in DSD models could provide an important step towards improving DSD implementation.

Cost-effectiveness of a direct to beneficiary mobile communication programme in improving reproductive and child health outcomes in India.

INTRODUCTION: Kilkari is the largest maternal messaging programme of its kind globally. Between its initiation in 2012 in Bihar and its transition to the government in 2019, Kilkari was scaled to 13 states across India and reached over 10 million new and expectant mothers and their families. This study aims to determine the cost-effectiveness of exposure to Kilkari as compared with no exposure across 13 states in India. METHODS: The study was conducted from a programme perspective using an analytic time horizon aligned with national scale-up efforts from December 2014 to April 2019. Economic costs were derived from the financial records of implementing partners. Data on incremental changes in the practice of reproductive maternal newborn and child health (RMNCH) outcomes were drawn from an individually randomised controlled trial in Madhya Pradesh and inputted into the Lives Saved Tool to yield estimates of maternal and child lives saved. One-way and probabilistic sensitivity analyses were carried out to assess uncertainty. RESULTS: Inflation adjusted programme costs were US$8.4 million for the period of December 2014-April 2019, corresponding to an average cost of US$264 298 per year of implementation in each state. An estimated 13 842 lives were saved across 13 states, 96% among children and 4% among mothers. The cost per life saved ranged by year of implementation and with the addition of new states from US$392 ($385-$393) to US$953 ($889-$1092). Key drivers included call costs and incremental changes in coverage for key RMNCH practices. CONCLUSION: Kilkari is highly cost-effective using a threshold of India's national gross domestic product of US$1998. Study findings provide important evidence on the cost-effectiveness of a national maternal messaging programme in India. TRIAL REGISTRATION: NCT03576157.

Contribution of Reinfection to Annual Rate of Tuberculosis Infection (ARI) and Incidence of Tuberculosis Disease.

BACKGROUND: Modeling studies have concluded that 60-80% of tuberculosis (TB) infections result from reinfection of previously infected persons. The annual rate of infection (ARI), a standard measure of the risk of TB infection in a community, may not accurately reflect the true risk of infection among previously infected persons. We constructed a model of infection and reinfection with Mycobacterium tuberculosis to explore the predictive accuracy of ARI and its effect on disease incidence. METHODS: We created a deterministic simulation of the progression from TB infection to disease and simulated the prevalence of TB infection at the beginning and end of a theoretical year of infection. We considered 10 disease prevalence scenarios ranging from 100/100 000 to 1000/100 000 in simulations where TB exposure probability was homogeneous across the whole simulated population or heterogeneously stratified into high-risk and low-risk groups. ARI values, rates of progression from infection to disease, and the effect of multiple reinfections were obtained from published studies. RESULTS: With homogeneous exposure risk, observed ARI values produced expected numbers of infections. However, when heterogeneous risk was introduced, observed ARI was seen to underestimate true ARI by 25-58%. Of the cases of TB disease that occurred, 36% were among previously infected persons when prevalence was 100/100 000, increasing to 79% of cases when prevalence was 1000/100 000. CONCLUSIONS: Measured ARI underestimates true ARI as a result of heterogeneous population mixing. The true force of infection in a community may be greater than previously appreciated. Hyperendemic communities likely contribute disproportionally to the global TB disease burden.

Optimal Social Distancing Policy for COVID-19 Control in Korea: A Model-Based Analysis.

BACKGROUND: Since March 2020, when coronavirus disease 2019 (COVID-19) was declared a pandemic, many countries have applied unprecedented restrictive measures to contain the spread of the virus. This study aimed to explore the optimal social distancing policy for COVID-19 control in South Korea to safely reopen the society. METHODS: We developed an age-specific, deterministic compartment epidemic model to examine the COVID-19 control decision-making process, including the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 July 2021 and 30 December 2022. The model consists of the natural history of COVID-19, testing performance, vaccinations, and social distancing enforcement measures to detect and control SARS-CoV-2. We modelled potential intervention scenarios with three distinct components: 1) social distancing duration and level; 2) testing intensity; and 3) vaccination uptake rate. The primary and secondary outcomes were COVID-19 incidence and prevalence of severe patients requiring intensive care unit (ICU) care. RESULTS: Four (or more) months of social distancing (that can reduce 40-60% transmission) may mitigate epidemic resurgence and ICU demand in the future and keep the cases below the capacity limit if the testing intensity and vaccination rate remain constant or increase by 20% (with respect to the current level). In contrast, two months of strict social distancing enforcement may also successfully mitigate future epidemic surge and ICU demand as long as testing intensity and vaccination rates are increased by 20%. CONCLUSION: In South Korea, given the relatively high vaccination coverage and low incidence, four or more months of social distancing enforcement can effectively mitigate epidemic resurgence after lifting the social distancing measures. In addition, increasing the testing intensity and vaccination rate may help reduce necessary social distancing levels and duration to prevent a future epidemic resurgence and mitigate social and economic damage.

Model-based cost-effectiveness analysis of oral antivirals against SARS-CoV-2 in Korea.

OBJECTIVES: Many countries have authorized the emergency use of oral antiviral agents for patients with mild-to-moderate cases of coronavirus disease 2019 (COVID-19). We assessed the cost-effectiveness of these agents for reducing the number of severe COVID-19 cases and the burden on Korea's medical system. METHODS: Using an existing model, we estimated the number of people who would require hospital/intensive care unit (ICU) admission in Korea in 2022. The treatment scenarios included (1) all adult patients, (2) elderly patients only, and (3) adult patients with underlying diseases only, compared to standard care. Based on the current health system capacity, we calculated the incremental costs per severe case averted and hospital admission for each scenario. RESULTS: We estimated that 236,510 COVID-19 patients would require hospital/ICU admission in 2022 with standard care only. Nirmatrelvir/ritonavir (87% efficacy) was predicted to reduce this number by 80%, 24%, and 17% when targeting all adults, adults with underlying diseases, and elderly patients (25, 8, and 4%, respectively, for molnupiravir, with 30% efficacy). Nirmatrelvir/ritonavir use is likely to be cost-effective, with predicted costs of US$8,878, US$8,964, and US$1,454, per severe patient averted for the target groups listed above, respectively, while molnupiravir is likely to be less cost-effective, with costs of US$28,492, US$29,575, and US$7,915, respectively. CONCLUSIONS: In Korea, oral treatment using nirmatrelvir/ritonavir for symptomatic COVID-19 patients targeting elderly patients would be highly cost-effective and would substantially reduce the demand for hospital admission to below the capacity of the health system if targeted to all adult patients instead of standard care.

Correction: The Potential of Digital Data Collection Tools for Long-lasting Insecticide-Treated Net Mass Campaigns in Nigeria: Formative Study.

[This corrects the article DOI: 10.2196/23648.].

The Potential of Digital Data Collection Tools for Long-lasting Insecticide-Treated Net Mass Campaigns in Nigeria: Formative Study.

BACKGROUND: Nigeria has the world's largest malaria burden, accounting for 27% of the world's malaria cases and 23% of malaria mortality globally. This formative study describes the operational process of the mass distribution of long-lasting insecticide-treated nets (LLINs) during a campaign program in Nigeria. OBJECTIVE: This study aims to assess whether and how digital data collection and management tools can change current practices and help resolve major implementation issues. METHODS: Qualitative data on the technical features and operational processes of paper-based and information and communication technology (ICT)-based systems in the Edo and Kwara states from June 2 to 30, 2017, were collected on the basis of documented operation manuals, field observations, and informant interviews. During the LLIN campaign in Edo State, we recruited 6 local government area focal persons and monitors and documented daily review meetings during household mobilization (9 days) and net distribution (5 days) to understand the major program implementation issues associated with the following three aspects: logistic issues, technical issues, and demand creation. Each issue was categorized according to the expected degree (low, mid, and high) of change by the ICT system. RESULTS: The net campaign started with microplanning and training, followed by a month-long implementation process, which included household mobilization, net movement, net distribution, and end process monitoring. The ICT system can improve management and oversight issues related to data reporting and processes through user-centered interface design, built-in data quality control logic flow or algorithms, and workflow automation. These often require more than 50% of staff time and effort in the current paper-based practice. Compared with the current paper-based system, the real-time system is expected to reduce the time to payment compensation for health workers by about 20 days and produce summary campaign statistics for at least 20 to 30 days. CONCLUSIONS: The ICT system can facilitate the measurement of population coverage beyond program coverage during an LLIN campaign with greater data reliability and timeliness, which are often compromised due to the limited workforce capacity in a paper-based system.

Changes in HIV treatment differentiated care uptake during the COVID-19 pandemic in Zambia: interrupted time series analysis.

INTRODUCTION: Differentiated service delivery (DSD) models aim to improve the access of human immunodeficiency virus treatment on clients and reduce requirements for facility visits by extending dispensing intervals. With the advent of the COVID-19 pandemic, minimising client contact with healthcare facilities and other clients, while maintaining treatment continuity and avoiding loss to care, has become more urgent, resulting in efforts to increase DSD uptake. We assessed the extent to which DSD coverage and antiretroviral treatment (ART) dispensing intervals have changed during the COVID-19 pandemic in Zambia. METHODS: We used client data from Zambia's electronic medical record system (SmartCare) for 737 health facilities, representing about three-fourths of all ART clients nationally. We compared the numbers and proportional distributions of clients enrolled in DSD models in the 6 months before and 6 months after the first case of COVID-19 was diagnosed in Zambia in March 2020. Segmented linear regression was used to determine whether the outbreak of COVID-19 in Zambia further accelerated the increase in DSD scale-up. RESULTS AND DISCUSSION: Between September 2019 and August 2020, 181,317 clients aged 15 or older (81,520 and 99,797 from 1 September 2019 to 1 March 2020 and from 1 March to 31 August 2020, respectively) enrolled in DSD models in Zambia. Overall participation in all DSD models increased over the study period, but uptake varied by model. The rate of acceleration increased in the second period for home ART delivery (152%), ≤ 2-month fast-track (143%) and 3-month MMD (139%). There was a significant reduction in the enrolment rates for 4- to 6-month fast-track (-28%) and "other" models (-19%). CONCLUSIONS: Participation in DSD models for stable ART clients in Zambia increased after the advent of COVID-19, but dispensing intervals diminished. Eliminating obstacles to longer dispensing intervals, including those related to supply chain management, should be prioritized to achieve the expected benefits of DSD models and minimize COVID-19 risk.

Costs and cost-effectiveness of a comprehensive tuberculosis case finding strategy in Zambia.

INTRODUCTION: Active-case finding (ACF) programs have an important role in addressing case detection gaps and halting tuberculosis (TB) transmission. Evidence is limited on the cost-effectiveness of ACF interventions, particularly on how their value is impacted by different operational, epidemiological and patient care-seeking patterns. METHODS: We evaluated the costs and cost-effectiveness of a combined facility and community-based ACF intervention in Zambia that utilized mobile chest X-ray with computer-aided reading/interpretation software and laboratory-based Xpert MTB/RIF testing. Programmatic costs (in 2018 US dollars) were assessed from the health system perspective using prospectively collected cost and operational data. Cost-effectiveness of the ACF intervention was assessed as the incremental cost per TB death averted over a five-year time horizon using a multi-stage Markov state-transition model reflecting patient symptom-associated care-seeking and TB care under ACF compared to passive care. RESULTS: Over 18 months of field operations, the ACF intervention costed $435 to diagnose and initiate treatment for one person with TB. After accounting for patient symptom-associated care-seeking patterns in Zambia, we estimate that this one-time ACF intervention would incrementally diagnose 407 (7,207 versus 6,800) TB patients and avert 502 (611 versus 1,113) TB-associated deaths compared to the status quo (passive case finding), at an incremental cost of $2,284 per death averted over the next five-year period. HIV/TB mortality rate, patient symptom-associated care-seeking probabilities in the absence of ACF, and the costs of ACF patient screening were key drivers of cost-effectiveness. CONCLUSIONS: A one-time comprehensive ACF intervention simultaneously operating in public health clinics and corresponding catchment communities can have important medium-term impact on case-finding and be cost-effective in Zambia. The value of such interventions increases if targeted to populations with high HIV/TB mortality, substantial barriers (both behavioral and physical) to care-seeking exist, and when ACF interventions can optimize screening by achieving operational efficiency.

mCARE, a digital health intervention package on pregnancy surveillance and care-seeking reminders from 2018 to 2027 in Bangladesh: a model-based cost-effectiveness analysis.

OBJECTIVE: We estimated the cost-effectiveness of a digital health intervention package (mCARE) for community health workers, on pregnancy surveillance and care-seeking reminders compared with the existing paper-based status quo, from 2018 to 2027, in Bangladesh. INTERVENTIONS: The mCARE programme involved digitally enhanced pregnancy surveillance, individually targeted text messages and in-person home-visit to pregnant women for care-seeking reminders for antenatal care, child delivery and postnatal care. STUDY DESIGN: We developed a model to project population and service coverage increases with annual geographical expansion (from 1 million to 10 million population over 10 years) of the mCARE programme and the status quo. MAJOR OUTCOMES: For this modelling study, we used Lives Saved Tool to estimate the number of deaths and disability-adjusted life years (DALYs) that would be averted by 2027, if the coverage of health interventions was increased in mCARE programme and the status quo, respectively. Economic costs were captured from a societal perspective using an ingredients approach and expressed in 2018 US dollars. Probabilistic sensitivity analysis was undertaken to account for parameter uncertainties. RESULTS: We estimated the mCARE programme to avert 3076 deaths by 2027 at an incremental cost of $43 million relative to the status quo, which is translated to $462 per DALY averted. The societal costs were estimated to be $115 million for mCARE programme (48% of which are programme costs, 35% user costs and 17% provider costs). With the continued implementation and geographical scaling-up, the mCARE programme improved its cost-effectiveness from $1152 to $462 per DALY averted from 5 to 10 years. CONCLUSION: Mobile phone-based pregnancy surveillance systems with individually scheduled text messages and home-visit reminder strategies can be highly cost-effective in Bangladesh. The cost-effectiveness may improve as it promotes facility-based child delivery and achieves greater programme cost efficiency with programme scale and sustainability.

Cost-effectiveness of Remdesivir and Dexamethasone for COVID-19 Treatment in South Africa.

BACKGROUND: Dexamethasone and remdesivir have the potential to reduce coronavirus disease 2019 (COVID)-related mortality or recovery time, but their cost-effectiveness in countries with limited intensive care resources is unknown. METHODS: We projected intensive care unit (ICU) needs and capacity from August 2020 to January 2021 using the South African National COVID-19 Epi Model. We assessed the cost-effectiveness of (1) administration of dexamethasone to ventilated patients and remdesivir to nonventilated patients, (2) dexamethasone alone to both nonventilated and ventilated patients, (3) remdesivir to nonventilated patients only, and (4) dexamethasone to ventilated patients only, all relative to a scenario of standard care. We estimated costs from the health care system perspective in 2020 US dollars, deaths averted, and the incremental cost-effectiveness ratios of each scenario. RESULTS: Remdesivir for nonventilated patients and dexamethasone for ventilated patients was estimated to result in 408 (uncertainty range, 229-1891) deaths averted (assuming no efficacy [uncertainty range, 0%-70%] of remdesivir) compared with standard care and to save $15 million. This result was driven by the efficacy of dexamethasone and the reduction of ICU-time required for patients treated with remdesivir. The scenario of dexamethasone alone for nonventilated and ventilated patients requires an additional $159 000 and averts 689 [uncertainty range, 330-1118] deaths, resulting in $231 per death averted, relative to standard care. CONCLUSIONS: The use of remdesivir for nonventilated patients and dexamethasone for ventilated patients is likely to be cost-saving compared with standard care by reducing ICU days. Further efforts to improve recovery time with remdesivir and dexamethasone in ICUs could save lives and costs in South Africa.

Cost-effectiveness of scaling up short course preventive therapy for tuberculosis among children across 12 countries.

BACKGROUND: While household contact investigation is widely recommended as a means to reduce the burden of tuberculosis (TB) among children, only 27% of eligible pediatric household contacts globally received preventive treatment in 2018. We assessed the cost-effectiveness of household contact investigation for TB treatment and short-course preventive therapy provision for children under 15 years old across 12 high TB burden countries. METHODS: We used decision analysis to compare the costs and estimated effectiveness of three intervention scenarios: (a) status quo (existing levels of coverage with isoniazid preventive therapy), (b) contact investigation with treatment of active TB but no additional preventive therapy, and (c) contact investigation with TB treatment and provision of short-course preventive therapy. Using country-specific demographic, epidemiological and cost data from the literature, we estimated annual costs (in 2018 USD) and the number of TB cases and deaths averted across 12 countries. Incremental cost effectiveness ratios were assessed as cost per death and per disability-adjusted life year [DALY] averted. FINDINGS: Our model estimates that contact investigation with treatment of active TB and provision of preventive therapy could be highly cost-effective compared to the status quo (ranging from $100 per DALY averted in Malawi to $1,600 in Brazil; weighted average $383 per DALY averted [uncertainty range: $248 - $1,130]) and preferred to contact investigation without preventive therapy (weighted average $751 per DALY averted [uncertainty range: $250 - $1,306]). Key drivers of cost-effectiveness were TB prevalence, sensitivity of TB diagnosis, case fatality for untreated TB, and cost of household screening. INTERPRETATION: Based on this modeling analysis of available published data, household contact investigation with provision of short-course preventive therapy for TB has a value-for-money profile that compares favorably with other interventions. FUNDING: Unitaid (2017-20-IMPAACT4TB).

Sub-district level correlation between tuberculosis notifications and socio-demographic factors in Dhaka City corporation, Bangladesh.

We developed a novel method to align two data sources (TB notifications and the Demographic Health Survey, DHS) captured at different geographic scales. We used this method to identify sociodemographic indicators - specifically population density - that were ecologically correlated with elevated TB notification rates across wards (~100 000 people) in Dhaka, Bangladesh. We found population density was the variable most closely correlated with ward-level TB notification rates (Spearman's rank correlation 0.45). Our approach can be useful, as publicly available data (e.g. DHS data) could help identify factors that are ecologically associated with disease burden when more granular data (e.g. ward-level TB notifications) are not available. Use of this approach might help in designing spatially targeted interventions for TB and other diseases in settings of weak existing data on disease burden at the subdistrict level.

Model-based Cost-effectiveness of State-level Latent Tuberculosis Interventions in California, Florida, New York, and Texas.

BACKGROUND: Targeted testing and treatment (TTT) for latent tuberculosis (TB) infection (LTBI) is a recommended strategy to accelerate TB reductions and further TB elimination in the United States. Evidence on cost-effectiveness of TTT for key populations can help advance this goal. METHODS: We used a model of TB transmission to estimate the numbers of individuals who could be tested by interferon-γ release assay and treated for LTBI with 3 months of self-administered rifapentine and isoniazid (3HP) under various TTT scenarios. Specifically, we considered rapidly scaling up TTT among people who are non-US-born, diabetic, living with human immunodeficiency virus (HIV), homeless or incarcerated in California, Florida, New York, and Texas-states where more than half of US TB cases occur. We projected costs (from the healthcare system perspective, in 2018 dollars), 30-year reductions in TB incidence, and incremental cost-effectiveness (cost per quality-adjusted life-year [QALY] gained) for TTT in each modeled population. RESULTS: The projected cost-effectiveness of TTT differed substantially by state and population, while the health impact (number of TB cases averted) was consistently greatest among non-US-born individuals. TTT was most cost-effective among persons with HIV (from $2828/QALY gained in Florida to $11 265/QALY gained in New York) and least cost-effective among people with diabetes (from $223 041/QALY gained in California to $817 753/QALY in New York). CONCLUSIONS: The modeled cost-effectiveness of TTT for LTBI varies across states but was consistently greatest among people with HIV; moderate among people who are non-US-born, incarcerated, or homeless; and least cost-effective among people with diabetes.

Incorporating patient reporting patterns to evaluate spatially targeted TB interventions.

PURPOSE: Tuberculosis (TB) is geographically heterogeneous, and geographic targeting can improve the impact of TB interventions. However, standard TB notification data may not sufficiently capture this heterogeneity. Better understanding of patient reporting patterns (discrepancies between residence and place of presentation) may improve our ability to use notifications to appropriately target interventions. METHODS: Using demographic data and TB reports from Dhaka North City Corporation and Dhaka South City Corporation, we identified wards of high TB incidence and developed a TB transmission model. We calibrated the model to patient-level data from selected wards under four different reporting pattern assumptions and estimated the relative impact of targeted versus untargeted active case finding. RESULTS: The impact of geographically targeted interventions varied substantially depending on reporting pattern assumptions. The relative reduction in TB incidence, comparing targeted with untargeted active case finding in Dhaka North City Corporation, was 1.20, assuming weak correlation between reporting and residence, versus 2.45, assuming perfect correlation. Similar patterns were observed in Dhaka South City Corporation (1.03 vs. 2.08). CONCLUSIONS: Movement of individuals seeking TB diagnoses may substantially affect ward-level TB transmission. Better understanding of patient reporting patterns can improve estimates of the impact of targeted interventions in reducing TB incidence. Incorporating high-quality patient-level data is critical to optimizing TB interventions.

Cost-effectiveness of one month of daily isoniazid and rifapentine versus three months of weekly isoniazid and rifapentine for prevention of tuberculosis among people receiving antiretroviral therapy in Uganda.

INTRODUCTION: Preventive therapy is essential for reducing tuberculosis (TB) burden among people living with HIV (PLWH) in high-burden settings. Short-course preventive therapy regimens, such as three-month weekly rifapentine and isoniazid (3HP) and one-month daily rifapentine and isoniazid (1HP), may help facilitate uptake of preventive therapy for latently infected patients, but the comparative cost-effectiveness of these regimens under different conditions is uncertain. METHODS: We used a Markov state-transition model to estimate the incremental costs and effectiveness of 1HP versus 3HP in a simulated cohort of patients attending an HIV clinic in Uganda, as an example of a low-income, high-burden setting in which TB preventive therapy might be prescribed to PLWH. Our primary outcome was the incremental cost-effectiveness ratio, expressed as 2019 US dollars per disability-adjusted life year (DALY) averted. We estimated cost-effectiveness under different conditions of treatment completion and efficacy of 1HP versus 3HP, latent TB prevalence and rifapentine price. RESULTS: Assuming equivalent clinical outcomes using 1HP and 3HP and a rifapentine price of $0.21 per 150 mg, 1HP would cost an additional $4.66 per patient treated. Assuming equivalent efficacy but 20% higher completion with 1HP versus 3HP, 1HP would cost $1,221 per DALY averted relative to 3HP. This could be reduced to $18 per DALY averted if 1HP had 5% greater efficacy than 3HP and the price of rifapentine were 50% lower. At a rifapentine price of $0.06 per 150 mg, 1HP would become cost-neutral relative to 3HP. CONCLUSIONS: 1HP has the potential to be cost-effective under many realistic circumstances. Cost-effectiveness depends on rifapentine price, relative completion and efficacy, prevalence of latent TB and local willingness-to-pay.

Cost-effectiveness of a 12 country-intervention to scale up short course TB preventive therapy among people living with HIV.

INTRODUCTION: In 2017, the Aurum Institute, with support from Unitaid, launched an initiative to expand short-course therapy for the prevention of tuberculosis (TB) in 12 high-burden countries. This study aimed to investigate the importance of "catalytic" effects beyond the original project timeframe when estimating cost-effectiveness of such large investments. METHODS: We estimated the cost-effectiveness of the IMPAACT4TB (I4TB) initiative from a health system perspective, using a 10-year time horizon. We first conservatively estimated costs using a "top-down" approach considering only the direct health benefits of providing TB preventive therapy to people initiating antiretroviral therapy (ART) through I4TB activities. We then re-estimated the incremental cost-effectiveness of I4TB incorporating the costs and health benefits of potential catalytic effects beyond the program itself. RESULTS: We estimated that TB preventive therapy through the I4TB initiative alone would prevent 14 201 cases of active TB and 1562 TB deaths over 10 years with an up-front investment of $52.5 million; the estimated incremental cost-effectiveness was $1580 per disability-adjusted life year (DALY) averted. If this initiative could achieve its desired catalytic effects, an additional 375 648 cases and 41 321 deaths could be averted, at an incremental cost of $546 million and cost-effectiveness of $713 per DALY averted. CONCLUSIONS: Our findings provide donors with reasonable evidence of value for money to support investment in short-course TB preventive therapy for people initiating ART in high-burden settings. Our study also illustrates the importance of considering long-term secondary ("catalytic") effects when evaluating the cost-effectiveness of large-scale initiatives designed to change a global policy landscape.

Cost-effectiveness of remdesivir and dexamethasone for COVID-19 treatment in South Africa.

Background South Africa recently experienced a first peak in COVID-19 cases and mortality. Dexamethasone and remdesivir both have the potential to reduce COVID-related mortality, but their cost-effectiveness in a resource-limited setting with scant intensive care resources is unknown. Methods We projected intensive care unit (ICU) needs and capacity from August 2020 to January 2021 using the South African National COVID-19 Epi Model. We assessed cost-effectiveness of 1) administration of dexamethasone to ventilated patients and remdesivir to non-ventilated patients, 2) dexamethasone alone to both non-ventilated and ventilated patients, 3) remdesivir to non-ventilated patients only, and 4) dexamethasone to ventilated patients only; all relative to a scenario of standard care. We estimated costs from the healthcare system perspective in 2020 USD, deaths averted, and the incremental cost effectiveness ratios of each scenario. Results Remdesivir for non-ventilated patients and dexamethasone for ventilated patients was estimated to result in 1,111 deaths averted (assuming a 0-30% efficacy of remdesivir) compared to standard care, and save $11.5 million. The result was driven by the efficacy of the drugs, and the reduction of ICU-time required for patients treated with remdesivir. The scenario of dexamethasone alone to ventilated and non-ventilated patients requires additional $159,000 and averts 1,146 deaths, resulting in $139 per death averted, relative to standard care. Conclusions The use of dexamethasone for ventilated and remdesivir for non-ventilated patients is likely to be cost-saving compared to standard care. Given the economic and health benefits of both drugs, efforts to ensure access to these medications is paramount.

Standardized framework for evaluating costs of active case-finding programs: An analysis of two programs in Cambodia and Tajikistan.

INTRODUCTION: Over the years, technological and process innovations enabled active case finding (ACF) programs to expand their capacities and scope to have evolved to close gaps in missing TB patients globally. However, with increased ACF program's operational complexity and a need for significant resource commitments, a comprehensive, transparent, and standardized approach in evaluating costs of ACF programs is needed to properly determine costs and value of ACF programs. METHODS: Based on reviews of program activity and financial reports, multiple interviews with program managers of two TB REACH funded ACF programs deployed in Cambodia and Tajikistan, we first identified common program components, which formed the basis of the cost data collection, analysis, reporting framework. Within each program component and sub-activity group, cost data were collected and organized by relevant resource types (human resource, capital, recurrent, and overhead costs). Total shared, indirect and overhead costs were apportioned into each activity category based on direct human resource contribution (e.g. a number of staff and their relative level of effort dedicated to each program component). Capital assets were assessed specific to program components and were annualized based on their expected useful life and a 3% discount rate. All costs were assessed based on the service provider perspective and expressed in 2015 USD. RESULTS: Over the two program years (April 2013 to December 2015), the Cambodia and Tajikistan ACF programs cumulated a total cost of $336,951 and $771,429 to screen 68,846 and 1,980,516 target population, bacteriologically test 4,589 and 19,764 presumptive TB, diagnose 731 and 2,246 TB patients in the respective programs. Recurrent costs were the largest cost components (54% and 34%) of the total costs for the respective programs and Xpert MTB/RIF (Xpert) testing incurred largest program component/activity cost for both programs. Cost per screening was $0.63 and $0.10 and cost per Xpert test was $25 and $18; Cost per TB case detected (Xpert) was $373 and $343 in Cambodia and Tajikistan. CONCLUSIONS: Results from two contextually and programmatically different multi-component ACF programs demonstrate that our tool is fully capable of comprehensively and transparently evaluating and comparing costs of various ACF programs.