Health Outcomes and Cost-effectiveness of Monoclonal SARS-CoV-2 Antibodies as Pre-exposure Prophylaxis

Importance: Pre-exposure prophylaxis with neutralizing SARS-CoV-2 monoclonal antibodies (mAbs PrEP) prevents infection and reduces hospitalizations and the duration thereof for COVID-19 and death among high-risk individuals. However, reduced effectiveness due to a changing SARS-CoV-2 viral landscape and high drug prices remain substantial implementation barriers. Objective: To assess the cost-effectiveness of mAbs PrEP as COVID-19 PrEP. Design, Setting, and Participants: For this economic evaluation, a decision analytic model was developed and parameterized with health care outcome and utilization data from individuals with high risk for COVID-19. The SARS-CoV-2 infection probability, mAbs PrEP effectiveness, and drug pricing were varied. All costs were collected from a third-party payer perspective. Data were analyzed from September 2021 to December 2022. Main Outcomes and Measures: Health care outcomes including new SARS-CoV-2 infections, hospitalization, and deaths. The cost per death averted and cost-effectiveness ratios using a threshold for prevention interventions of $22000 or less per quality-adjusted life year (QALY) gained. Results: The clinical cohort consisted of 636 individuals with COVID-19 (mean [SD] age 63 [18] years; 341 [54$275 and 75% or higher effectiveness. With a 100% effectiveness mAbs PrEP can reduce ward admissions by 70%, ICU admissions by 97%, and deaths by 92%. Drug prices, however, need to reduce to $550 for cost-effectiveness ratios less than$22000 per QALY gained per death averted and to $2200 for ratios between$22000 and $88000. Conclusions and Relevance: In this study, use of mAbs PrEP for preventing SARS-CoV-2 infections was cost-saving at the beginning of an epidemic wave (high infection probability) with 75$275. These results are timely and relevant for decision-makers involved in mAbs PrEP implementation. When newer mAbs PrEP combinations become available, guidance on implementation should be formulated ensuring a fast rollout. Nevertheless, advocacy for mAbs PrEP use and critical discussion on drug prices are necessary to ensuring cost-effectiveness for different epidemic settings.</p

Single-molecule transport at a rectifying GaAs contact

In most single- or few-molecule devices, the contact electrodes are simple ohmic resistors. Here we describe a new type of single-molecule device in which metal and semiconductor contact electrodes impart a function, namely, current rectification, which is then modified by a molecule bridging the gap. We study junctions with the structure Au STM tip/X/n-GaAs substrate, where "X" is either a simple alkanedithiol or a conjugated unit bearing thiol/methylthiol contacts, and we detect current jumps corresponding to the attachment and detachment of single molecules. From the magnitudes of the current jumps we can deduce values for the conductance decay constant with molecule length that agree well with values determined from Au/molecule/Au junctions. The ability to impart functionality to a single-molecule device through the properties of the contacts as well as through the properties of the molecule represents a significant extension of the single-molecule electronics "tool-box"

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

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

The role of remdesivir in South Africa : preventing COVID-19 deaths through increasing intensive care unit capacity

CITATION: Nichols, B. E. et al. 2020. The Role of Remdesivir in South Africa: Preventing COVID-19 Deaths Through Increasing Intensive Care Unit Capacity. Clinical Infectious Diseases: 72(9), 1642–1644, doi:10.1093/cid/ciaa937The original publication is available at https://academic.oup.com/cid/Countries such as South Africa have limited intensive care unit (ICU) capacity to handle the expected number of patients with COVID-19 requiring ICU care. Remdesivir can prevent deaths in countries such as South Africa by decreasing the number of days people spend in ICU, therefore freeing up ICU bed capacity.https://academic.oup.com/cid/article/72/9/1642/5868030?login=truePublishers versio

Health benefi ts, costs, and cost-eff ectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models

Background New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefi ts, costs, and cost-eff ectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. Methods We used several independent mathematical models in four settings—South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)—to assess the potential health benefi ts, costs, and cost-eff ectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost eff ective if the cost per DALY averted was less than the country’s 2012 per-head gross domestic product (GDP; South Africa:$8040; Zambia: $1425; India:$1489; Vietnam: $1407) and cost eff ective if the cost per DALY averted was less than three times the per-head GDP. Findings In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from$237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to$749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost eff ective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to$241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost eff ective. Interpretation Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost eff ective in lowincome and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets

Increasing the use of second-line therapy is a cost-effective approach to prevent the spread of drug-resistant HIV: a mathematical modelling study

METHODS: We develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10-year period. We then compare the impact on TDR and cost-effectiveness of: (1) introduction of pre-therapy genotyping; (2) doubling use of second-line treatment to 80% (50-90%) of patients with confirmed virological failure on first-line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost-effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than $3420 in Uganda.RESULTS: The prevalence of TDR is predicted to rise from 6.7$1612 to $2234 (IQR$450-dominated) per QALY gained.CONCLUSIONS: While earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug-resistant HIV, the absolute numbers of patients infected with drug-resistant HIV is predicted to decrease. Increasing use of second-line treatment to all patients with confirmed failure on first-line therapy is a cost-effective approach to reduce TDR. Improving access to second-line ART is therefore a major priority.INTRODUCTION: Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR

Initial implementation of PrEP in Zambia: health policy development and service delivery scale-up

INTRODUCTION: Daily pre-exposure prophylaxis (PrEP) for HIV prevention is highly effective, but not yet widely deployed in sub-Saharan Africa. We describe how Zambia developed PrEP health policy and then successfully implemented national PrEP service delivery. POLICY DEVELOPMENT: Zambia introduced PrEP as a key strategy for HIV prevention in 2016, and established a National PrEP Task Force to lead policy advocacy and development. The Task Force was composed of government representatives, regulatory agencies, international donors, implementation partners and civil society organisations. Following an implementation pilot, PrEP was rolled out nationally using risk-based criteria alongside a national HIV prevention campaign. NATIONAL SCALE-UP: In the first year of implementation, ending September 2018, 3626 persons initiated PrEP. By September 2019, the number of people starting PrEP increased by over sixfold to 23 327 persons at 728 sites across all ten Zambian provinces. In the first 2 years, 26 953 clients initiated PrEP in Zambia, of whom 31% were from key and priority populations. Continuation remains low at 25% and 11% at 6 and 12 months, respectively. LESSONS LEARNT: Risk-based criteria for PrEP ensures access to those most in need of HIV prevention. Healthcare worker training in PrEP service delivery and health needs of key and priority populations is crucial. PrEP expansion into primary healthcare clinics and community education is required to reach full potential. Additional work is needed to understand and address low PrEP continuation. Finally, a task force of key stakeholders can rapidly develop and implement health policy, which may serve as a model for countries seeking to implement PrEP

Assessing fitness-for-purpose and comparing the suitability of COVID-19 multi-country models for local contexts and users

Background: Mathematical models have been used throughout the COVID-19 pandemic to inform policymaking decisions. The COVID-19 Multi-Model Comparison Collaboration (CMCC) was established to provide country governments, particularly low- and middle-income countries (LMICs), and other model users with an overview of the aims, capabilities and limits of the main multi-country COVID-19 models to optimise their usefulness in the COVID-19 response. Methods: Seven models were identified that satisfied the inclusion criteria for the model comparison and had creators that were willing to participate in this analysis. A questionnaire, extraction tables and interview structure were developed to be used for each model, these tools had the aim of capturing the model characteristics deemed of greatest importance based on discussions with the Policy Group. The questionnaires were first completed by the CMCC Technical group using publicly available information, before further clarification and verification was obtained during interviews with the model developers. The fitness-for-purpose flow chart for assessing the appropriateness for use of different COVID-19 models was developed jointly by the CMCC Technical Group and Policy Group. Results: A flow chart of key questions to assess the fitness-for-purpose of commonly used COVID-19 epidemiological models was developed, with focus placed on their use in LMICs. Furthermore, each model was summarised with a description of the main characteristics, as well as the level of engagement and expertise required to use or adapt these models to LMIC settings. Conclusions: This work formalises a process for engagement with models, which is often done on an ad-hoc basis, with recommendations for both policymakers and model developers and should improve modelling use in policy decision making

Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models.

BACKGROUND: New WHO guidelines recommend ART initiation for HIV-positive persons with CD4 cell counts ≤500 cells/µL, a higher threshold than was previously recommended. Country decision makers must consider whether to further expand ART eligibility accordingly. METHODS: We used multiple independent mathematical models in four settings-South Africa, Zambia, India, and Vietnam-to evaluate the potential health impact, costs, and cost-effectiveness of different adult ART eligibility criteria under scenarios of current and expanded treatment coverage, with results projected over 20 years. Analyses considered extending eligibility to include individuals with CD4 ≤500 cells/µL or all HIV-positive adults, compared to the previous recommendation of initiation with CD4 ≤350 cells/µL. We assessed costs from a health system perspective, and calculated the incremental cost per DALY averted ($/DALY) to compare competing strategies. Strategies were considered 'very cost-effective' if the$/DALY was less than the country's per capita gross domestic product (GDP; South Africa: $8040, Zambia:$1425, India: $1489, Vietnam:$1407) and 'cost-effective' if $/DALY was less than three times per capita GDP. FINDINGS: In South Africa, the cost per DALY averted of extending ART eligibility to CD4 ≤500 cells/µL ranged from$237 to $1691/DALY compared to 2010 guidelines; in Zambia, expanded eligibility ranged from improving health outcomes while reducing costs (i.e. dominating current guidelines) to$749/DALY. Results were similar in scenarios with substantially expanded treatment access and for expanding eligibility to all HIV-positive adults. Expanding treatment coverage in the general population was therefore found to be cost-effective. In India, eligibility for all HIV-positive persons ranged from $131 to$241/DALY and in Vietnam eligibility for CD4 ≤500 cells/µL cost $290/DALY. In concentrated epidemics, expanded access among key populations was also cost-effective. INTERPRETATION: Earlier ART eligibility is estimated to be very cost-effective in low- and middle-income settings, although these questions should be revisited as further information becomes available. Scaling-up ART should be considered among other high-priority health interventions competing for health budgets. FUNDING: The Bill and Melinda Gates Foundation and World Health Organization