Scaling up target regimens for tuberculosis preventive treatment in Brazil and South Africa: An analysis of costs and cost-effectiveness.

BACKGROUND: Shorter, safer, and cheaper tuberculosis (TB) preventive treatment (TPT) regimens will enhance uptake and effectiveness. WHO developed target product profiles describing minimum requirements and optimal targets for key attributes of novel TPT regimens. We performed a cost-effectiveness analysis addressing the scale-up of regimens meeting these criteria in Brazil, a setting with relatively low transmission and low HIV and rifampicin-resistant TB (RR-TB) prevalence, and South Africa, a setting with higher transmission and higher HIV and RR-TB prevalence. METHODS AND FINDINGS: We used outputs from a model simulating scale-up of TPT regimens meeting minimal and optimal criteria. We assumed that drug costs for minimal and optimal regimens were identical to 6 months of daily isoniazid (6H). The minimal regimen lasted 3 months, with 70% completion and 80% efficacy; the optimal regimen lasted 1 month, with 90% completion and 100% efficacy. Target groups were people living with HIV (PLHIV) on antiretroviral treatment and household contacts (HHCs) of identified TB patients. The status quo was 6H at 2019 coverage levels for PLHIV and HHCs. We projected TB cases and deaths, TB-associated disability-adjusted life years (DALYs), and costs (in 2020 US dollars) associated with TB from a TB services perspective from 2020 to 2035, with 3% annual discounting. We estimated the expected costs and outcomes of scaling up 6H, the minimal TPT regimen, or the optimal TPT regimen to reach all eligible PLHIV and HHCs by 2023, compared to the status quo. Maintaining current 6H coverage in Brazil (0% of HHCs and 30% of PLHIV treated) would be associated with 1.1 (95% uncertainty range [UR] 1.1-1.2) million TB cases, 123,000 (115,000-132,000) deaths, and 2.5 (2.1-3.1) million DALYs and would cost $1.1 ($1.0-$1.3) billion during 2020-2035. Expanding the 6H, minimal, or optimal regimen to 100% coverage among eligible groups would reduce DALYs by 0.5% (95% UR 1.2% reduction, 0.4% increase), 2.5% (1.8%-3.0%), and 9.0% (6.5%-11.0%), respectively, with additional costs of $107 ($95-$117) million and $51 ($41-$60) million and savings of $36 ($14-$58) million, respectively. Compared to the status quo, costs per DALY averted were $7,608 and $808 for scaling up the 6H and minimal regimens, respectively, while the optimal regimen was dominant (cost savings, reduced DALYs). In South Africa, maintaining current 6H coverage (0% of HHCs and 69% of PLHIV treated) would be associated with 3.6 (95% UR 3.0-4.3) million TB cases, 843,000 (598,000-1,201,000) deaths, and 36.7 (19.5-58.0) million DALYs and would cost $2.5 ($1.8-$3.6) billion. Expanding coverage with the 6H, minimal, or optimal regimen would reduce DALYs by 6.9% (95% UR 4.3%-95%), 15.5% (11.8%-18.9%), and 38.0% (32.7%-43.0%), respectively, with additional costs of $79 (-$7, $151) million and $40 (-$52, $140) million and savings of $608 ($443-$832) million, respectively. Compared to the status quo, estimated costs per DALY averted were $31 and $7 for scaling up the 6H and minimal regimens, while the optimal regimen was dominant. Study limitations included the focus on 2 countries, and no explicit consideration of costs incurred before the decision to prescribe TPT. CONCLUSIONS: Our findings suggest that scale-up of TPT regimens meeting minimum or optimal requirements would likely have important impacts on TB-associated outcomes and would likely be cost-effective or cost saving.

Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study.

BACKGROUND: COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years. METHODS: Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic. FINDINGS: In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics. INTERPRETATION: Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council.

Assessing tuberculosis control priorities in high-burden settings: a modelling approach.

BACKGROUND: In the context of WHO's End TB strategy, there is a need to focus future control efforts on those interventions and innovations that would be most effective in accelerating declines in tuberculosis burden. Using a modelling approach to link the tuberculosis care cascade to transmission, we aimed to identify which improvements in the cascade would yield the greatest effect on incidence and mortality. METHODS: We engaged with national tuberculosis programmes in three country settings (India, Kenya, and Moldova) as illustrative examples of settings with a large private sector (India), a high HIV burden (Kenya), and a high burden of multidrug resistance (Moldova). We collated WHO country burden estimates, routine surveillance data, and tuberculosis prevalence surveys from 2011 (for India) and 2016 (for Kenya). Linking the tuberculosis care cascade to tuberculosis transmission using a mathematical model with Bayesian melding in each setting, we examined which cascade shortfalls would have the greatest effect on incidence and mortality, and how the cascade could be used to monitor future control efforts. FINDINGS: Modelling suggests that combined measures to strengthen the care cascade could reduce cumulative tuberculosis incidence by 38% (95% Bayesian credible intervals 27-43) in India, 31% (25-41) in Kenya, and 27% (17-41) in Moldova between 2018 and 2035. For both incidence and mortality, modelling suggests that the most important cascade losses are the proportion of patients visiting the private health-care sector in India, missed diagnosis in health-care settings in Kenya, and drug sensitivity testing in Moldova. In all settings, the most influential delay is the interval before a patient's first presentation for care. In future interventions, the proportion of individuals with tuberculosis who are on high-quality treatment could offer a more robust monitoring tool than routine notifications of tuberculosis. INTERPRETATION: Linked to transmission, the care cascade can be valuable, not only for improving patient outcomes but also in identifying and monitoring programmatic priorities to reduce tuberculosis incidence and mortality. FUNDING: US Agency for International Development, Stop TB Partnership, UK Medical Research Council, and Department for International Development.

Cost-Effectiveness of Accelerated HIV Response Scenarios in Côte d'Ivoire.

BACKGROUND: Despite Côte d'Ivoire epidemic being labeled as "generalized," key populations (KPs) are important to overall transmission. Using a dynamic model of HIV transmission, we previously estimated the impact of several treatment-as-prevention strategies that reached-or missed-the UNAIDS 90-90-90 targets in different populations groups, including KP and clients of female sex workers (CFSWs). To inform program planning and resources allocation, we assessed the cost-effectiveness of these scenarios. METHODS: Costing was performed from the provider's perspective. Unit costs were obtained from the Ivorian Programme national de lutte contre le Sida (USD 2015) and discounted at 3%. Net incremental cost-effectiveness ratios (ICER) per adult HIV infection prevented and per disability-adjusted life-years (DALY) averted were estimated over 2015-2030. RESULTS: The 3 most cost-effective and affordable scenarios were the ones that projected current programmatic trends [ICER = $210; 90% uncertainty interval (90% UI): $150-$300], attaining the 90-90-90 objectives among KP and CFSW (ICER = $220; 90% UI: $80-$510), and among KP only (ICER = $290; 90% UI: $90-$660). The least cost-effective scenario was the one that reached the UNAIDS 90-90-90 target accompanied by a 25% point drop in condom use in KP (ICER = $710; 90% UI: $450-$1270). In comparison, the UNAIDS scenario had a net ICER of $570 (90% UI: $390-$900) per DALY averted. CONCLUSIONS: According to commonly used thresholds, accelerating the HIV response can be considered very cost-effective for all scenarios. However, when balancing epidemiological impact, cost-effectiveness, and affordability, scenarios that sustain both high condom use and rates of viral suppression among KP and CFSW seem most promising in Côte d'Ivoire.