Cost-effectiveness of community-based household tuberculosis contact management for children in Cameroon and Uganda: a modelling analysis of a cluster-randomised trial.

BACKGROUND: WHO recommends household contact management (HCM) including contact screening and tuberculosis-preventive treatment (TPT) for eligible children. The CONTACT trial found increased TPT initiation and completion rates when community health workers were used for HCM in Cameroon and Uganda. METHODS: We did a cost-utility analysis of the CONTACT trial using a health-system perspective to estimate the health impact, health-system costs, and cost-effectiveness of community-based versus facility-based HCM models of care. A decision-analytical modelling approach was used to evaluate the cost-effectiveness of the intervention compared with the standard of care using trial data on cascade of care, intervention effects, and resource use. Health outcomes were based on modelled progression to tuberculosis, mortality, and discounted disability-adjusted life-years (DALYs) averted. Health-care resource use, outcomes, costs (2021 US$), and cost-effectiveness are presented. FINDINGS: For every 1000 index patients diagnosed with tuberculosis, the intervention increased the number of TPT courses by 1110 (95% uncertainty interval 894 to 1227) in Cameroon and by 1078 (796 to 1220) in Uganda compared with the control model. The intervention prevented 15 (-3 to 49) tuberculosis deaths in Cameroon and 10 (-20 to 33) in Uganda. The incremental cost-effectiveness ratio was $620 per DALY averted in Cameroon and $970 per DALY averted in Uganda. INTERPRETATION: Community-based HCM approaches can substantially reduce child tuberculosis deaths and in our case would be considered cost-effective at willingness-to-pay thresholds of $1000 per DALY averted. Their impact and cost-effectiveness are likely to be greatest where baseline HCM coverage is lowest. FUNDING: Unitaid and UK Medical Research Council.

Cost-effectiveness analysis of interventions to improve diagnosis and preventive therapy for paediatric tuberculosis in 9 sub-Saharan African countries: A modelling study.

BACKGROUND: Over 1 million children aged 0 to 14 years were estimated to develop tuberculosis in 2021, resulting in over 200,000 deaths. Practical interventions are urgently needed to improve diagnosis and antituberculosis treatment (ATT) initiation in children aged 0 to 14 years and to increase coverage of tuberculosis preventive therapy (TPT) in children at high risk of developing tuberculosis disease. The multicountry CaP-TB intervention scaled up facility-based intensified case finding and strengthened household contact management and TPT provision at HIV clinics. To add to the limited health-economic evidence on interventions to improve ATT and TPT in children, we evaluated the cost-effectiveness of the CaP-TB intervention. METHODS AND FINDINGS: We analysed clinic-level pre/post data to quantify the impact of the CaP-TB intervention on ATT and TPT initiation across 9 sub-Saharan African countries. Data on tuberculosis diagnosis and ATT/TPT initiation counts with corresponding follow-up time were available for 146 sites across the 9 countries prior to and post project implementation, stratified by 0 to 4 and 5 to 14 year age-groups. Preintervention data were retrospectively collected from facility registers for a 12-month period, and intervention data were prospectively collected from December 2018 to June 2021 using project-specific forms. Bayesian generalised linear mixed-effects models were used to estimate country-level rate ratios for tuberculosis diagnosis and ATT/TPT initiation. We analysed project expenditure and cascade data to determine unit costs of intervention components and used mathematical modelling to project health impact, health system costs, and cost-effectiveness. Overall, ATT and TPT initiation increased, with country-level incidence rate ratios varying between 0.8 (95% uncertainty interval [UI], 0.7 to 1.0) and 2.9 (95% UI, 2.3 to 3.6) for ATT and between 1.6 (95% UI, 1.5 to 1.8) and 9.8 (95% UI, 8.1 to 11.8) for TPT. We projected that for every 100 children starting either ATT or TPT at baseline, the intervention package translated to between 1 (95% UI, -1 to 3) and 38 (95% UI, 24 to 58) deaths averted, with a median incremental cost-effectiveness ratio (ICER) of US$634 per disability-adjusted life year (DALY) averted. ICERs ranged between US$135/DALY averted in Democratic of the Congo and US$6,804/DALY averted in Cameroon. The main limitation of our study is that the impact is based on pre/post comparisons, which could be confounded. CONCLUSIONS: In most countries, the CaP-TB intervention package improved tuberculosis treatment and prevention services for children aged under 15 years, but large variation in estimated impact and ICERs highlights the importance of local context. TRIAL REGISTRATION: This evaluation is part of the TIPPI study, registered with ClinicalTrials.gov (NCT03948698).

2021 World Health Organization guideline on pharmacological treatment of hypertension: Policy implications for the region of the Americas.

Cardiovascular disease (CVD) is the leading cause of death in the Americas and raised blood pressure accounts for over 50% of CVD. In the Americas over a quarter of adult women and four in ten adult men have hypertension and the diagnosis, treatment and control are suboptimal. In 2021, the World Health Organization (WHO) released an updated guideline for the pharmacological treatment of hypertension in adults. This policy paper highlights the facilitating role of the WHO Global HEARTS initiative and the HEARTS in the Americas initiative to catalyze the implementation of this guideline, provides specific policy advice for implementation, and emphasizes that an overarching strategic approach for hypertension control is needed. The authors urge health advocates and policymakers to prioritize the prevention and control of hypertension to improve the health and wellbeing of their populations and to reduce CVD health disparities within and between populations of the Americas.

[2021 World Health Organization guideline on pharmacological treatment of hypertension: Policy implications for the Region of the AmericasDirectrices de la Organización Mundial de la Salud del 2021 sobre el tratamiento farmacológico de la hipertensión: implicaciones de política para la Región de las Américas]. / Diretrizes de 2021 da Organização Mundial da Saúde sobre o tratamento medicamentoso da hipertensão arterial: repercussões para as políticas na Região das Américas.

Cardiovascular disease (CVD) is the leading cause of death in the Americas and raised blood pressure accounts for over 50% of CVD. In the Americas over a quarter of adult women and four in ten adult men have hypertension and the diagnosis, treatment and control are suboptimal. In 2021, the World Health Organization (WHO) released an updated guideline for the pharmacological treatment of hypertension in adults. This policy paper highlights the facilitating role of the WHO Global HEARTS initiative and the HEARTS in the Americas initiative to catalyze the implementation of this guideline, provides specific policy advice for implementation, and emphasizes that an overarching strategic approach for hypertension control is needed. The authors urge health advocates and policymakers to prioritize the prevention and control of hypertension to improve the health and wellbeing of their populations and to reduce CVD health disparities within and between populations of the Americas.

Las enfermedades cardiovasculares son la principal causa de muerte en la Región de las Américas y la hipertensión es la causa de más del 50% de ellas. En la Región, más de una cuarta parte de las mujeres adultas y cuatro de cada diez hombres adultos tienen hipertensión y su diagnóstico, tratamiento y control son deficientes. En el 2021, la Organización Mundial de la Salud (OMS) publicó directrices actualizadas sobre el tratamiento farmacológico de la hipertensión en personas adultas. En este artículo se destaca el papel facilitador de la iniciativa mundial HEARTS de la OMS y la iniciativa HEARTS en las Américas para catalizar la implementación de estas directrices, a la vez que se proporciona asesoramiento específico sobre políticas para dicha implementación y se destaca la necesidad de adoptar un enfoque estratégico general para el control de la hipertensión. Los autores instan a quienes abogan por la salud y a los responsables de las políticas a priorizar la prevención y el control de la hipertensión para mejorar la salud y el bienestar de la población, y a reducir las disparidades de salud en relación con las enfermedades cardiovasculares dentro de la población y entre las poblaciones de la Región de las Américas.

[2021 World Health Organization guideline on pharmacological treatment of hypertension: Policy implications for the region of the AmericasDiretrizes de 2021 da Organização Mundial da Saúde sobre o tratamento medicamentoso da hipertensão arterial: repercussões para as políticas na região das Américas]. / Directrices de la Organización Mundial de la Salud del 2021 sobre el tratamiento farmacológico de la hipertensión: implicaciones de política para la Región de las Américas.

Cardiovascular disease (CVD) is the leading cause of death in the Americas and raised blood pressure accounts for over 50% of CVD. In the Americas over a quarter of adult women and four in ten adult men have hypertension and the diagnosis, treatment and control are suboptimal. In 2021, the World Health Organization (WHO) released an updated guideline for the pharmacological treatment of hypertension in adults. This policy paper highlights the facilitating role of the WHO Global HEARTS initiative and the HEARTS in the Americas initiative to catalyze the implementation of this guideline, provides specific policy advice for implementation, and emphasizes that an over-arching strategic approach for hypertension control is needed. The authors urge health advocates and policymakers to prioritize the prevention and control of hypertension to improve the health and wellbeing of their populations and to reduce CVD health disparities within and between populations of the Americas.

A doença cardiovascular (DCV) é a principal causa de morte nas Américas, e a pressão arterial elevada é responsável por mais de 50% dos casos de DCV. Nas Américas, mais de um quarto das mulheres adultas e quatro de cada dez homens adultos têm hipertensão arterial, sendo que diagnóstico, tratamento e controle estão abaixo do ideal. Em 2021, a Organização Mundial da Saúde (OMS) divulgou uma atualização das diretrizes para o tratamento medicamentoso da hipertensão arterial em adultos. Essa publicação ressalta o papel facilitador da iniciativa Global HEARTS da OMS e da iniciativa HEARTS nas Américas para catalisar a implementação dessas diretrizes, oferece recomendações específicas de políticas para sua implementação e enfatiza a necessidade de uma abordagem estratégica abrangente para o controle da hipertensão arterial. Os autores clamam para que tanto as pessoas que advogam pela Saúde, quanto as autoridades responsáveis, priorizem a prevenção e o controle da hipertensão arterial como forma de melhorar a saúde e o bem-estar das populações e reduzir as disparidades de saúde cardiovascular dentro das populações das Américas e entre elas.

A simple six-step guide to National-Scale Hypertension Control Program implementation.

Hypertension is the leading single preventable risk factor for death worldwide, and most of the disease burden attributed to hypertension weighs on low-and middle-income countries. Effective large-scale public health hypertension control programs are needed to control hypertension globally. National programs can follow six important steps to launch a successful national-scale hypertension control program: establish an administrative structure and survey current resources, select a standard hypertension treatment protocol, ensure supply of medication and blood pressure devices, train health care workers to measure blood pressure and control hypertension, implement an information system for monitoring patients and the program overall, and enroll and monitor patients with phased program expansion. Resolve to Save Lives, an initiative of global public health organization Vital Strategies, and its partners organized these six key steps and materials into a structured, stepwise guide to establish best practices in hypertension program design, launch, maintenance, and scale-up.

Diretrizes de 2021 da Organização Mundial da Saúde sobre o tratamento medicamentoso da hipertensão arterial: repercussões para as políticas na Região das Américas / 2021 World Health Organization guideline on pharmacological treatment of hypertension: Policy implications for the Region of the Americas / Directrices de la Organización Mundial de la Salud del 2021 sobre el tratamiento farmacológico de la hipertensión: implicaciones de política para la Región de las Américas

RESUMO A doença cardiovascular (DCV) é a principal causa de morte nas Américas, e a pressão arterial elevada é responsável por mais de 50% dos casos de DCV. Nas Américas, mais de um quarto das mulheres adultas e quatro de cada dez homens adultos têm hipertensão arterial, sendo que diagnóstico, tratamento e controle estão abaixo do ideal. Em 2021, a Organização Mundial da Saúde (OMS) divulgou uma atualização das diretrizes para o tratamento medicamentoso da hipertensão arterial em adultos. Esta publicação ressalta o papel facilitador da iniciativa Global HEARTS da OMS e da iniciativa HEARTS nas Américas para catalisar a implementação dessas diretrizes, oferece recomendações específicas de políticas para sua implementação e enfatiza a necessidade de uma abordagem estratégica abrangente para o controle da hipertensão arterial. Os autores clamam para que tanto as pessoas que advogam pela Saúde, quanto as autoridades responsáveis, priorizem a prevenção e o controle da hipertensão arterial como forma de melhorar a saúde e o bem-estar das populações e reduzir as disparidades de saúde cardiovascular dentro das populações das Américas e entre elas.

ABSTRACT Cardiovascular disease (CVD) is the leading cause of death in the Americas and raised blood pressure accounts for over 50% of CVD. In the Americas over a quarter of adult women and four in ten adult men have hypertension and the diagnosis, treatment and control are suboptimal. In 2021, the World Health Organization (WHO) released an updated guideline for the pharmacological treatment of hypertension in adults. This policy paper highlights the facilitating role of the WHO Global HEARTS initiative and the HEARTS in the Americas initiative to catalyze the implementation of this guideline, provides specific policy advice for implementation, and emphasizes that an overarching strategic approach for hypertension control is needed. The authors urge health advocates and policymakers to prioritize the prevention and control of hypertension to improve the health and wellbeing of their populations and to reduce CVD health disparities within and between populations of the Americas.

RESUMEN Las enfermedades cardiovasculares son la principal causa de muerte en la Región de las Américas y la hipertensión es la causa de más del 50% de ellas. En la Región, más de una cuarta parte de las mujeres adultas y cuatro de cada diez hombres adultos tienen hipertensión y su diagnóstico, tratamiento y control son deficientes. En el 2021, la Organización Mundial de la Salud (OMS) publicó directrices actualizadas sobre el tratamiento farmacológico de la hipertensión en personas adultas. En este artículo se destaca el papel facilitador de la iniciativa mundial HEARTS de la OMS y la iniciativa HEARTS en las Américas para catalizar la implementación de estas directrices, a la vez que se proporciona asesoramiento específico sobre políticas para dicha implementación y se destaca la necesidad de adoptar un enfoque estratégico general para el control de la hipertensión. Los autores instan a quienes abogan por la salud y a los responsables de las políticas a priorizar la prevención y el control de la hipertensión para mejorar la salud y el bienestar de la población, y a reducir las disparidades de salud en relación con las enfermedades cardiovasculares dentro de la población y entre las poblaciones de la Región de las Américas.

Directrices de la Organización Mundial de la Salud del 2021 sobre el tratamiento farmacológico de la hipertensión: implicaciones de política para la Región de las Américas / 2021 World Health Organization guideline on pharmacological treatment of hypertension: Policy implications for the region of the Americas / Diretrizes de 2021 da Organização Mundial da Saúde sobre o tratamento medicamentoso da hipertensão arterial: repercussões para as políticas na região das Américas

RESUMEN Las enfermedades cardiovasculares son la principal causa de muerte en la Región de las Américas y la hipertensión es la causa de más del 50% de ellas. En la Región, más de una cuarta parte de las mujeres adultas y cuatro de cada diez hombres adultos tienen hipertensión y su diagnóstico, tratamiento y control son deficientes. En el 2021, la Organización Mundial de la Salud (OMS) publicó directrices actualizadas sobre el tratamiento farmacológico de la hipertensión en personas adultas. En este artículo se destaca el papel facilitador de la iniciativa mundial HEARTS de la OMS y la iniciativa HEARTS en las Américas para catalizar la implementación de estas directrices, a la vez que se proporciona asesoramiento específico sobre políticas para dicha implementación y se destaca la necesidad de adoptar un enfoque estratégico general para el control de la hipertensión. Los autores instan a quienes abogan por la salud y a los responsables de las políticas a priorizar la prevención y el control de la hipertensión para mejorar la salud y el bienestar de la población, y a reducir las disparidades de salud en relación con las enfermedades cardiovasculares dentro de la población y entre las poblaciones de la Región de las Américas.

ABSTRACT Cardiovascular disease (CVD) is the leading cause of death in the Americas and raised blood pressure accounts for over 50% of CVD. In the Americas over a quarter of adult women and four in ten adult men have hypertension and the diagnosis, treatment and control are suboptimal. In 2021, the World Health Organization (WHO) released an updated guideline for the pharmacological treatment of hypertension in adults. This policy paper highlights the facilitating role of the WHO Global HEARTS initiative and the HEARTS in the Americas initiative to catalyze the implementation of this guideline, provides specific policy advice for implementation, and emphasizes that an over-arching strategic approach for hypertension control is needed. The authors urge health advocates and policymakers to prioritize the prevention and control of hypertension to improve the health and wellbeing of their populations and to reduce CVD health disparities within and between populations of the Americas.

RESUMO A doença cardiovascular (DCV) é a principal causa de morte nas Américas, e a pressão arterial elevada é responsável por mais de 50% dos casos de DCV. Nas Américas, mais de um quarto das mulheres adultas e quatro de cada dez homens adultos têm hipertensão arterial, sendo que diagnóstico, tratamento e controle estão abaixo do ideal. Em 2021, a Organização Mundial da Saúde (OMS) divulgou uma atualização das diretrizes para o tratamento medicamentoso da hipertensão arterial em adultos. Essa publicação ressalta o papel facilitador da iniciativa Global HEARTS da OMS e da iniciativa HEARTS nas Américas para catalisar a implementação dessas diretrizes, oferece recomendações específicas de políticas para sua implementação e enfatiza a necessidade de uma abordagem estratégica abrangente para o controle da hipertensão arterial. Os autores clamam para que tanto as pessoas que advogam pela Saúde, quanto as autoridades responsáveis, priorizem a prevenção e o controle da hipertensão arterial como forma de melhorar a saúde e o bem-estar das populações e reduzir as disparidades de saúde cardiovascular dentro das populações das Américas e entre elas.

Implementation of differentiated service delivery for paediatric HIV care and treatment: opportunities, challenges and experience from seven sub-Saharan African countries.

Differentiated service delivery (DSD) models for HIV often exclude children and adolescents. Given that children and adolescents have lower rates of HIV diagnosis, treatment and viral load suppression, there is a need to use DSD to meet the needs of children and adolescents living with HIV. This commentary reviews the concept of DSD, examines the application of DSD to the care of children and adolescents living with HIV, and describes national guidance on use of DSD for children and adolescents and implementation of DSD for HIV care and treatment in children and adolescents in Elizabeth Glaser Pediatric AIDS Foundation (EGPAF)-supported programmes in seven sub-Saharan countries between 2017 and 2019. Programme descriptions include eligibility criteria, location and frequency of care delivery, healthcare cadre delivering the care, as well as the number of EGPAF-supported facilities supporting each type of DSD model. A range of DSD models were identified. While facility-based models predominate, several countries support community-based models. Despite significant uptake of various DSD models for children and adolescents, there was variable coverage within countries and variability in age criteria for each model. While the recent uptake of DSD models for children and adolescents suggests feasibility, more can be done to optimise and extend the use of DSD models for children and adolescents living with HIV. Barriers to further DSD uptake are described and solutions proposed. DSD models for children and adolescents are a critical tool that can be optimised to improve the quality of HIV care and outcomes for children and adolescents.

Priority Actions to Advance Population Sodium Reduction.

High sodium intake is estimated to cause approximately 3 million deaths per year worldwide. The estimated average sodium intake of 3.95 g/day far exceeds the recommended intake. Population sodium reduction should be a global priority, while simultaneously ensuring universal salt iodization. This article identifies high priority strategies that address major sources of sodium: added to packaged food, added to food consumed outside the home, and added in the home. To be included, strategies needed to be scalable and sustainable, have large benefit, and applicable to one of four measures of effectiveness: (1) Rigorously evaluated with demonstrated success in reducing sodium; (2) suggestive evidence from lower quality evaluations or modeling; (3) rigorous evaluations of similar interventions not specifically for sodium reduction; or (4) an innovative approach for sources of sodium that are not sufficiently addressed by an existing strategy. We identified seven priority interventions. Four target packaged food: front-of-pack labeling, packaged food reformulation targets, regulating food marketing to children, and taxes on high sodium foods. One targets food consumed outside the home: food procurement policies for public institutions. Two target sodium added at home: mass media campaigns and population uptake of low-sodium salt. In conclusion, governments have many tools to save lives by reducing population sodium intake.

Strengthening Existing Laboratory-Based Systems vs. Investing in Point-of-Care Assays for Early Infant Diagnosis of HIV: A Model-Based Cost-Effectiveness Analysis.

BACKGROUND: To improve early infant HIV diagnosis (EID) programs, options include replacing laboratory-based tests with point-of-care (POC) assays or investing in strengthened systems for sample transport and result return. SETTING: We used the CEPAC-Pediatric model to examine clinical benefits and costs of 3 EID strategies in Zimbabwe for infants 6 weeks of age. METHODS: We examined (1) laboratory-based EID (LAB), (2) strengthened laboratory-based EID (S-LAB), and (3) POC EID (POC). LAB/S-LAB and POC assays differed in sensitivity (LAB/S-LAB 100%, POC 96.9%) and specificity (LAB/S-LAB 99.6%, POC 99.9%). LAB/S-LAB/POC algorithms also differed in: probability of result return (79%/91%/98%), time until result return (61/53/1 days), probability of initiating antiretroviral therapy (ART) after positive result (52%/71%/86%), and total cost/test ($18.10/$30.47/$30.71). We projected life expectancy (LE) and average lifetime per-person cost for all HIV-exposed infants. We calculated incremental cost-effectiveness ratios (ICERs) from discounted (3%/year) LE and costs in $/year-of-life saved (YLS), defining cost effective as an ICER <$580/YLS (reflecting programs providing 2 vs. 1 ART regimens). In sensitivity analyses, we varied differences between S-LAB and POC in result return probability, result return time, ART initiation probability, and cost. RESULTS: For infants who acquired HIV, LAB/S-LAB/POC led to projected one-year survival of 67.3%/69.9%/75.6% and undiscounted LE of 21.74/22.71/24.49 years. For all HIV-exposed infants, undiscounted LE was 63.35/63.38/63.43 years, at discounted lifetime costs of $200/220/240 per infant. In cost-effectiveness analysis, S-LAB was an inefficient use of resources; the ICER of POC vs. LAB was $830/YLS. CONCLUSIONS: Current EID programs will attain greater benefit from investing in POC EID rather than strengthening laboratory-based systems.

Acceptability of Routine Point-of-Care Early Infant Diagnosis in Eight African Countries: Findings From a Qualitative Assessment of Clinical and Laboratory Personnel.

BACKGROUND: The Elizabeth Glaser Pediatric AIDS Foundation introduced point-of-care (POC) testing for early infant diagnosis (EID) of HIV in 8 African countries. Understanding experiences and opinions of users can help facilitate introduction and sustainability. SETTING: Cameroon, Côte d'Ivoire, Eswatini, Kenya, Lesotho, Mozambique, Rwanda, and Zimbabwe. METHODS: Structured interviews with health care workers (HCWs) providing EID services and semistructured interviews with national and regional laboratory managers or EID program managers were conducted before and after the implementation of POC EID. Survey responses were analyzed and compared; open-ended responses were analyzed by theme. RESULTS: In total, 234 and 175 interviews with HCWs and 28 and 14 interviews with laboratory or program managers were conducted before and after the introduction of POC EID, respectively. In preintervention interviews, challenges identified with laboratory-based EID testing included distance from patients' residence to the health facility, time-consuming sample transportation to central laboratories, stockout of testing kits, and long wait times for results. Postintervention data revealed that HCWs found POC EID easy to use and were very satisfied with the fast turnaround time and ability to initiate treatment for HIV-infected infants sooner. Laboratory managers were also supportive of scaling-up POC testing although cautious of the need for reliable infrastructure to operate platforms. The recommendation was that POC EID be integrated within the national diagnostic testing network. CONCLUSIONS: Support for POC EID from key stakeholders is essential for sustainability. Overall, participants supported the rollout of POC testing for EID, noting challenges and opportunities for scaling-up POC EID and recommending integration into the overall EID system.

Estimating the Cost of Point-of-Care Early Infant Diagnosis in a Program Setting: A Case Study Using Abbott m-PIMA and Cepheid GeneXpert IV in Zimbabwe.

BACKGROUND: Point-of-care early infant diagnosis (POC EID) increases access to HIV test results and shortens time to result-return and antiretroviral therapy initiation, as compared to central laboratory-based EID. However, to scale-up POC EID, governments need more information about programmatic costs. METHODS: We evaluated POC EID costs from a health systems perspective. Our primary analysis assessed the Abbott m-PIMA and 2 versions of the Cepheid GeneXpert IV platforms-with a solar battery or gel battery-used in Zimbabwe, with instrument purchase. We also included the following 2 scenarios with zero upfront equipment purchase: (1) m-PIMA using a reagent rental model, with an all-inclusive price when the buyer commits to an average testing volume, and (2) GeneXpert IV, reflecting contexts where GeneXpert is already in place for tuberculosis diagnosis or HIV viral load monitoring. We collected data from project expenditures, observations of health workers, and from government salary scales. We calculated cost per EID test based on number of EID tests performed on each machine per day. RESULTS: The cost per successfully completed test was $44.55 for m-PIMA with platform purchase and $25.89 for m-PIMA reagent rental. Costs for GeneXpert IV with platform purchase were $25.70 using a solar battery, $25.29 using a gel battery, and $23.85 under a scenario assuming no equipment costs. In our primary analyses, materials costs comprised 73%-74% total costs, equipment 14%-20%, labor 5%-8%, training 1%, facility upgrades 1%, and monitoring 1%. CONCLUSIONS: As countries consider scaling up POC EID, these data are important for budgeting and planning.

Integrating pediatric TB services into child healthcare services in Africa: study protocol for the INPUT cluster-randomized stepped wedge trial.

BACKGROUND: Tuberculosis is among the top-10 causes of mortality in children with more than 1 million children suffering from TB disease annually worldwide. The main challenge in young children is the difficulty in establishing an accurate diagnosis of active TB. The INPUT study is a stepped-wedge cluster-randomized intervention study aiming to assess the effectiveness of integrating TB services into child healthcare services on TB diagnosis capacities in children under 5 years of age. METHODS: Two strategies will be compared: i) The standard of care, offering pediatric TB services based on national standard of care; ii) The intervention, with pediatric TB services integrated into child healthcare services: it consists of a package of training, supportive supervision, job aids, and logistical support to the integration of TB screening and diagnosis activities into pediatric services. The design is a cluster-randomized stepped-wedge of 12 study clusters in Cameroon and Kenya. The sites start enrolling participants under standard-of-care and will transition to the intervention at randomly assigned time points. We enroll children aged less than 5 years with a presumptive diagnosis of TB after obtaining caregiver written informed consent. The participants are followed through TB diagnosis and treatment, with clinical information prospectively abstracted from their medical records. The primary outcome is the proportion of TB cases diagnosed among children < 5 years old attending the child healthcare services. Secondary outcomes include: number of children screened for presumptive active TB; diagnosed; initiated on TB treatment; and completing treatment. We will also assess the cost-effectiveness of the intervention, its acceptability among health care providers and users, and fidelity of implementation. DISCUSSION: Study enrolments started in May 2019, enrolments will be completed in October 2020 and follow up will be completed by June 2021. The study findings will be disseminated to national, regional and international audiences and will inform innovative approaches to integration of TB screening, diagnosis, and treatment initiation into child health care services. TRIAL RESISTRATION: NCT03862261, initial release 12 February 2019.

Updated assessment of risks and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines.

BACKGROUND: The integrase inhibitor dolutegravir is being considered in several countries in sub-Saharan Africa instead of efavirenz for people initiating antiretroviral therapy (ART) because of superior tolerability and a lower risk of resistance emergence. WHO requested updated modelling results for its 2019 Antiretroviral Guidelines update, which was restricted to the choice of dolutegravir or efavirenz in new ART initiators. In response to this request, we modelled the risks and benefits of alternative policies for initial first-line ART regimens. METHODS: We updated an existing individual-based model of HIV transmission and progression in adults to consider information on the risk of neural tube defects in women taking dolutegravir at time of conception, as well as the effects of dolutegravir on weight gain. The model accounted for drug resistance in determining viral suppression, with consequences for clinical outcomes and mother-to-child transmission. We sampled distributions of parameters to create various epidemic setting scenarios, which reflected the diversity of epidemic and programmatic situations in sub-Saharan Africa. For each setting scenario, we considered the situation in 2018 and compared ART initiation policies of an efavirenz-based regimen in women intending pregnancy, and a dolutegravir-based regimen in others, and a dolutegravir-based regimen, including in women intending pregnancy. We considered predicted outcomes over a 20-year period from 2019 to 2039, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted. FINDINGS: Considering updated information on risks and benefits, a policy of ART initiation with a dolutegravir-based regimen rather than an efavirenz-based regimen, including in women intending pregnancy, is predicted to bring population health benefits (10 990 DALYs averted per year) and to be cost-saving (by $2·9 million per year), leading to a reduction in the overall population burden of disease of 16 735 net DALYs per year for a country with an adult population size of 10 million. The policy involving ART initiation with a dolutegravir-based regimen in women intending pregnancy was cost-effective in 87% of our setting scenarios and this finding was robust in various sensitivity analyses, including around the potential negative effects of weight gain. INTERPRETATION: In the context of a range of modelled setting scenarios in sub-Saharan Africa, we found that a policy of ART initiation with a dolutegravir-based regimen, including in women intending pregnancy, was predicted to bring population health benefits and be cost-effective, supporting WHO's strong recommendation for dolutegravir as a preferred drug for ART initiators. FUNDING: Bill & Melinda Gates Foundation.

Evaluation of a routine point-of-care intervention for early infant diagnosis of HIV: an observational study in eight African countries.

BACKGROUND: In 2017, there were 180 000 estimated new HIV infections in children aged 0-14 years. Without early diagnosis and treatment, half of infants with HIV die by age 2 years, with peak mortality around age 8-10 weeks. Conventional early infant diagnosis (EID) systems have not consistently returned results in a timely manner. However, point-of-care (POC) EID devices, which are new to market, could improve outcomes. In December, 2016, POC EID testing was introduced in eight sub-Saharan African countries as part of routine service delivery. We aimed to compare key service delivery and clinical outcomes and costs of POC versus conventional EID. METHODS: In our observational study, we compared service delivery and clinical outcomes in eight countries (Cameroon, Côte d'Ivoire, Kenya, Lesotho, Mozambique, Rwanda, Swaziland, and Zimbabwe), before and after a POC intervention was introduced for EID of HIV. For the baseline, pre-intervention sample, we sampled 30 consecutive tests for HIV-exposed infants who had a documented date of blood collection for EID within Ministry of Health registers in a subset of Elizabeth Glaser Pediatric AIDS Foundation (EGPAF)-supported sites that would be enrolled in POC. For the post-intervention sample, all infants who were tested with POC EID for HIV at an EGPAF site were included in the sample. For both conventional and POC EID testing, we did not specify an age range, but used national EID guidelines for EID eligibility. A range of sites for conventional data collection were selected to represent both primary testing sites (where POC EID instruments would be placed) and spoke sites, rural and urban environment, and high throughput and low throughput sites. In all countries, except Mozambique, we developed a POC EID test request form in conjunction with the Ministry of Health. In Mozambique, EGPAF-trained staff extracted data from health facility registers and other sources using a data collection form. Certain specific indicators were required for all countries, but countries could collect additional variables, as the POC EID test request form was used for patient management for the duration of the project. These forms were filled in by health-care providers at the facility. Once the form was completed it was collected by EGPAF staff and entered into a project-specific database. The cost per test result returned was approximated by use of the Global Fund's total cost of ownership estimates. FINDINGS: Retrospective collection of data on clinical and service delivery outcomes of conventional testing began on Nov 14, 2016, and was completed on Nov 26, 2017, for tests done between March 3, 2014, and March 30, 2017, at 96 health-care facilities using conventional testing. POC tests were done at 339 health-care facilities between Dec 1, 2016, and Dec 31, 2017. We evaluated data from 2875 infants exposed to HIV who were tested with conventional testing methods (2899 tests) and 18 220 infants tested with POC testing (19 071 tests). Several EID outcomes were significantly improved with POC testing relative to conventional testing. The return of results to caregivers within 30 days (in 18 737 [98·3%] of 19 058 infants receiving POC testing vs 542 [18·7%] of 2898 infants receiving conventional testing; p<0·0001), the median time from sample collection to return of results to caregivers (0 vs 55 days; p<0·0001), the number of infants with HIV initiating antiretroviral therapy (ART) within 60 days of sample collection (639 [92·3%] of 692 infants vs 42 [43·3%] of 97 infants; p<0·0001), the median time from sample collection to ART initiation among infants with HIV (0 vs 49 days; p<0·0001), and the median age at ART initiation among infants with HIV who were tested at 6-8 weeks (1·6 vs 3·3 months; p<0·0001) were all improved with POC testing compared with conventional testing. The cost per test result returned within 30 days was less for POC (US$27·24, range 21·39-33·10) than conventional testing ($131·02, 96·26-165·76). INTERPRETATION: POC EID improves the speed of return of HIV test results and enables earlier ART initiation; this approach could potentially reduce morbidity and mortality in infants with HIV. National programmes, funders, and implementing partners should consider POC EID as a preferred testing strategy for implementation. FUNDING: Unitaid.

Clinical effect and cost-effectiveness of incorporation of point-of-care assays into early infant HIV diagnosis programmes in Zimbabwe: a modelling study.

BACKGROUND: New point-of-care (POC) assays for early infant HIV diagnosis are costlier than conventional total nucleic acid assays, but could increase access to testing, shorten time to results, and expedite initiation of antiretroviral therapy. We aimed to assess the clinical benefits and cost-effectiveness of incorporating these POC assays into early infant diagnosis programmes in Zimbabwe. METHODS: We used the Cost Effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model to examine the clinical benefits, costs, and cost-effectiveness of replacing conventional assays for early infant HIV diagnosis with POC assays at age 6 weeks in Zimbabwe. We simulated two strategies for early infant HIV diagnosis: conventional and POC. Modelled assays differed in sensitivity; specificity; time to, and probability of, return of results; and cost. Model outcomes included survival, life expectancy, and mean lifetime per-person treatment cost, which were reported separately for all HIV-exposed infants and all infants with HIV. We calculated incremental cost-effectiveness ratios with discounted (3% per year) costs and life expectancy from a health-care system perspective for all HIV-exposed infants. We judged incremental cost-effectiveness ratios of $1010 (Zimbabwe's annual gross domestic product per person) or less per year of life saved to be cost-effective. FINDINGS: When conventional assays were used for early infant diagnosis, projected undiscounted life expectancy was 22·7 years for infants with HIV and 62·5 years for all HIV-exposed infants, at a cost of $610 per HIV-exposed infant. Use of POC assays for early infant HIV diagnosis improved projected undiscounted life expectancy to 25·5 years among infants with HIV and 62·6 years among HIV-exposed infants at a cost of $690 per HIV-exposed infant. At age 12 weeks, survival among all infants with HIV was 76·1% with the conventional testing strategy and 83·5% with the POC testing strategy. The incremental cost-effectiveness ratio of POC assays versus conventional assays for early infant diagnosis was $680 per year of life saved. When conventional assay characteristics remained constant, this ratio remained under the cost-effectiveness threshold as long as the specificity and sensitivity of the POC assay were greater than 92% and 65%, respectively. Our results were robust to plausible variations in POC assay cost, the probability of ART initiation, and probability of return of the results of POC testing. INTERPRETATION: Compared with conventional assays, POC assays for early infant HIV diagnosis in Zimbabwe will improve survival, extend life expectancy, and be cost-effective for HIV-exposed infants. FUNDING: Elizabeth Glaser Pediatric AIDS Foundation, US National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Unitaid.

Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries.

In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.

Scale-up of Routine Viral Load Testing in Resource-Poor Settings: Current and Future Implementation Challenges.

Despite immense progress in antiretroviral therapy (ART) scale-up, many people still lack access to basic standards of care, with our ability to meet the Joint United Nations Programme on HIV/AIDS 90-90-90 treatment targets for HIV/AIDS dependent on dramatic improvements in diagnostics. The World Health Organization recommends routine monitoring of ART effectiveness using viral load (VL) testing at 6 months and every 12 months, to monitor treatment adherence and minimize failure, and will publish its VL toolkit later this year. However, the cost and complexity of VL is preventing scale-up beyond developed countries and there is a lack of awareness among clinicians as to the long-term patient benefits and its role in prolonging the longevity of treatment programs. With developments in this diagnostic field rapidly evolving-including the recent improvements for accurately using dried blood spots and the imminent appearance to the market of point-of-care technologies offering decentralized diagnosis-we describe current barriers to VL testing in resource-limited settings. Effective scale-up can be achieved through health system and laboratory system strengthening and test price reductions, as well as tackling multiple programmatic and funding challenges.

Sustainable HIV treatment in Africa through viral-load-informed differentiated care.

There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.