Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization.

BACKGROUND: WHO, as requested by its member states, launched the Expanded Programme on Immunization (EPI) in 1974 to make life-saving vaccines available to all globally. To mark the 50-year anniversary of EPI, we sought to quantify the public health impact of vaccination globally since the programme's inception. METHODS: In this modelling study, we used a suite of mathematical and statistical models to estimate the global and regional public health impact of 50 years of vaccination against 14 pathogens in EPI. For the modelled pathogens, we considered coverage of all routine and supplementary vaccines delivered since 1974 and estimated the mortality and morbidity averted for each age cohort relative to a hypothetical scenario of no historical vaccination. We then used these modelled outcomes to estimate the contribution of vaccination to globally declining infant and child mortality rates over this period. FINDINGS: Since 1974, vaccination has averted 154 million deaths, including 146 million among children younger than 5 years of whom 101 million were infants younger than 1 year. For every death averted, 66 years of full health were gained on average, translating to 10·2 billion years of full health gained. We estimate that vaccination has accounted for 40% of the observed decline in global infant mortality, 52% in the African region. In 2024, a child younger than 10 years is 40% more likely to survive to their next birthday relative to a hypothetical scenario of no historical vaccination. Increased survival probability is observed even well into late adulthood. INTERPRETATION: Since 1974 substantial gains in childhood survival have occurred in every global region. We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50 years. In the context of strengthening primary health care, our results show that equitable universal access to immunisation remains crucial to sustain health gains and continue to save future lives from preventable infectious mortality. FUNDING: WHO.

A case for ongoing structural support to maximise infectious disease modelling efficiency for future public health emergencies: A modelling perspective.

This short communication reflects upon the challenges and recommendations of multiple COVID-19 modelling and data analytic groups that provided quantitative evidence to support health policy discussions in Switzerland and Germany during the SARS-CoV-2 pandemic. Capacity strengthening outside infectious disease emergencies will be required to enable an environment for a timely, efficient, and data-driven response to support decisions during any future infectious disease emergency. This will require 1) a critical mass of trained experts who continuously advance state-of-the-art methodological tools, 2) the establishment of structural liaisons amongst scientists and decision-makers, and 3) the foundation and management of data-sharing frameworks.

COVID-19 Vaccine Booster Strategies in Light of Emerging Viral Variants: Frequency, Timing, and Target Groups.

BACKGROUND: Vaccinations have reduced severe burden of COVID-19 and allowed for lifting of non-pharmaceutical interventions. However, with immunity waning alongside emergence of more transmissible variants of concern, vaccination strategies must be examined. METHODS: Here we apply a SARS-CoV-2 transmission model to identify preferred frequency, timing, and target groups for vaccine boosters to reduce public health burden and health systems risk. We estimated new infections and hospital admissions averted over 2 years through annual or biannual boosting of those eligible (those who received doses one and two) who are (1) most vulnerable (60+ or living with comorbidities) or (2) those 5+, at universal (98% of eligible) or lower coverage (85% of those 50+ or with comorbidities and 50% of 5-49 year olds) representing moderate vaccine fatigue and/or hesitancy. We simulated three emerging variant scenarios: (1) no new variants; (2) 25% more infectious and immune-evading Omicron-level severity variants emerge annually and become dominant; (3) emerge biannually. We further explored the impact of varying seasonality, variant immune-evading capacity, infectivity, severity, timing, and vaccine infection blocking assumptions. RESULTS: To reduce COVID-19-related hospitalisations over the next 2 years, boosters should be provided for all those eligible annually 3-4 months ahead of peak winter whether or not new variants of concern emerge. Only boosting those most vulnerable is unlikely to ensure reduced stress on health systems. Moreover, boosting all eligible better protects those most vulnerable than only boosting the vulnerable group. Conversely, while this strategy may not ensure reduced stress on health systems, as an indication of cost-effectiveness, per booster dose more hospitalisations could be averted through annual boosting of those most vulnerable versus all eligible, since those most vulnerable are more likely to seek hospital care once infected, whereas increasing to biannual boosting showed diminishing returns. Results were robust when key model parameters were varied. However, we found that the more frequently variants emerge, the less the effect boosters will have, regardless of whether administered annually or biannually. CONCLUSIONS: Delivering well-timed annual COVID-19 vaccine boosters to all those eligible, prioritising those most vulnerable, can reduce infections and hospital admissions. Findings provide model-based evidence for decision-makers to plan for administering COVID-19 boosters ahead of winter 2022-2023 to help mitigate the health burden and health system stress.

Modelling the impact of Omicron and emerging variants on SARS-CoV-2 transmission and public health burden.

Background: SARS-CoV-2 variants of concern, such as Omicron (B.1.1.529), continue to emerge. Assessing the impact of their potential viral properties on the probability of future transmission dominance and public health burden is fundamental in guiding ongoing COVID-19 control strategies. Methods: With an individual-based transmission model, OpenCOVID, we simulated three viral properties; infectivity, severity, and immune-evading ability, all relative to the Delta variant, to identify thresholds for Omicron's or any emerging VOC's potential future dominance, impact on public health, and risk to health systems. We further identify for which combinations of viral properties current interventions would be sufficient to control transmission. Results: We show that, with first-generation SARS-CoV-2 vaccines and limited physical distancing in place, a VOC's potential future dominance is primarily driven by its infectivity, which does not always lead to an increased public health burden. However, we also show that highly immune-evading variants that become dominant, even in the case of reduced variant severity, would likely require alternative measures to avoid strain on health systems, such as strengthened physical distancing measures, novel treatments, and second-generation vaccines. Expanded vaccination, that includes a booster dose for adults and child vaccination strategies, is projected to have the biggest public health benefit for a highly infective, highly severe VOC with low immune-evading capacity. Conclusions: These findings provide quantitative guidance to decision-makers at a critical time while Omicron's properties are being assessed and preparedness for emerging VOCs is eminent. We emphasise the importance of both genomic and population epidemiological surveillance.

The influence of biological, epidemiological, and treatment factors on the establishment and spread of drug-resistant Plasmodium falciparum.

The effectiveness of artemisinin-based combination therapies (ACTs) to treat Plasmodium falciparum malaria is threatened by resistance. The complex interplay between sources of selective pressure-treatment properties, biological factors, transmission intensity, and access to treatment-obscures understanding how, when, and why resistance establishes and spreads across different locations. We developed a disease modelling approach with emulator-based global sensitivity analysis to systematically quantify which of these factors drive establishment and spread of drug resistance. Drug resistance was more likely to evolve in low transmission settings due to the lower levels of (i) immunity and (ii) within-host competition between genotypes. Spread of parasites resistant to artemisinin partner drugs depended on the period of low drug concentration (known as the selection window). Spread of partial artemisinin resistance was slowed with prolonged parasite exposure to artemisinin derivatives and accelerated when the parasite was also resistant to the partner drug. Thus, to slow the spread of partial artemisinin resistance, molecular surveillance should be supported to detect resistance to partner drugs and to change ACTs accordingly. Furthermore, implementing more sustainable artemisinin-based therapies will require extending parasite exposure to artemisinin derivatives, and mitigating the selection windows of partner drugs, which could be achieved by including an additional long-acting drug.

Impact of vaccination and non-pharmaceutical interventions on SARS-CoV-2 dynamics in Switzerland.

BACKGROUND: As vaccination coverage against SARS-CoV-2 increases amidst the emergence and spread of more infectious and potentially more deadly viral variants, decisions on timing and extent of relaxing effective, but unsustainable, non-pharmaceutical interventions (NPIs) need to be made. METHODS: An individual-based transmission model of SARS-CoV-2 dynamics, OpenCOVID, was developed to compare the impact of various vaccination and NPI strategies on the COVID-19 epidemic in Switzerland. OpenCOVID uses the Oxford Containment Health Index (OCHI) to quantify the stringency of NPIs. RESULTS: Even if NPIs in place in March 2021 were to be maintained and the vaccine campaigns rollout rapidly scaled-up, a 'third wave' was predicted. However, we find a cautious phased relaxation can substantially reduce population-level morbidity and mortality. We find that a faster vaccination campaign can offset the size of such a wave, allowing more flexibility for NPIs to be relaxed sooner. Model outcomes were most sensitive to the level of infectiousness of variants of concern observed in Switzerland. CONCLUSION: A rapid vaccination rollout can allow the sooner relaxation of NPIs, however ongoing surveillance of - and swift responses to - emerging viral variants is of utmost importance for epidemic control.

How should HIV resources be allocated? Lessons learnt from applying Optima HIV in 23 countries.

INTRODUCTION: With limited funds available, meeting global health targets requires countries to both mobilize and prioritize their health spending. Within this context, countries have recognized the importance of allocating funds for HIV as efficiently as possible to maximize impact. Over the past six years, the governments of 23 countries in Africa, Asia, Eastern Europe and Latin America have used the Optima HIV tool to estimate the optimal allocation of HIV resources. METHODS: Each study commenced with a request by the national government for technical assistance in conducting an HIV allocative efficiency study using Optima HIV. Each study team validated the required data, calibrated the Optima HIV epidemic model to produce HIV epidemic projections, agreed on cost functions for interventions, and used the model to calculate the optimal allocation of available funds to best address national strategic plan targets. From a review and analysis of these 23 country studies, we extract common themes around the optimal allocation of HIV funding in different epidemiological contexts. RESULTS AND DISCUSSION: The optimal distribution of HIV resources depends on the amount of funding available and the characteristics of each country's epidemic, response and targets. Universally, the modelling results indicated that scaling up treatment coverage is an efficient use of resources. There is scope for efficiency gains by targeting the HIV response towards the populations and geographical regions where HIV incidence is highest. Across a range of countries, the model results indicate that a more efficient allocation of HIV resources could reduce cumulative new HIV infections by an average of 18% over the years to 2020 and 25% over the years to 2030, along with an approximately 25% reduction in deaths for both timelines. However, in most countries this would still not be sufficient to meet the targets of the national strategic plan, with modelling results indicating that budget increases of up to 185% would be required. CONCLUSIONS: Greater epidemiological impact would be possible through better targeting of existing resources, but additional resources would still be required to meet targets. Allocative efficiency models have proven valuable in improving the HIV planning and budgeting process.

The global Optima HIV allocative efficiency model: targeting resources in efforts to end AIDS.

BACKGROUND: To move towards ending AIDS by 2030, HIV resources should be allocated cost-effectively. We used the Optima HIV model to estimate how global HIV resources could be retargeted for greatest epidemiological effect and how many additional new infections could be averted by 2030. METHODS: We collated standard data used in country modelling exercises (including demographic, epidemiological, behavioural, programmatic, and expenditure data) from Jan 1, 2000, to Dec 31, 2015 for 44 countries, capturing 80% of people living with HIV worldwide. These data were used to parameterise separate subnational and national models within the Optima HIV framework. To estimate optimal resource allocation at subnational, national, regional, and global levels, we used an adaptive stochastic descent optimisation algorithm in combination with the epidemic models and cost functions for each programme in each country. Optimal allocation analyses were done with international HIV funds remaining the same to each country and by redistributing these funds between countries. FINDINGS: Without additional funding, if countries were to optimally allocate their HIV resources from 2016 to 2030, we estimate that an additional 7·4 million (uncertainty range 3·9 million-14·0 million) new infections could be averted, representing a 26% (uncertainty range 13-50%) incidence reduction. Redistribution of international funds between countries could avert a further 1·9 million infections, which represents a 33% (uncertainty range 20-58%) incidence reduction overall. To reduce HIV incidence by 90% relative to 2010, we estimate that more than a three-fold increase of current annual funds will be necessary until 2030. The most common priorities for optimal resource reallocation are to scale up treatment and prevention programmes targeting key populations at greatest risk in each setting. Prioritisation of other HIV programmes depends on the epidemiology and cost-effectiveness of service delivery in each setting as well as resource availability. INTERPRETATION: Further reductions in global HIV incidence are possible through improved targeting of international and national HIV resources. FUNDING: World Bank and Australian NHMRC.

Acute HIV infection detection and immediate treatment estimated to reduce transmission by 89% among men who have sex with men in Bangkok.

INTRODUCTION: Antiretroviral treatment (ART) reduces HIV transmission. Despite increased ART coverage, incidence remains high among men who have sex with men (MSM) in many places. Acute HIV infection (AHI) is characterized by high viral replication and increased infectiousness. We estimated the feasible reduction in transmission by targeting MSM with AHI for early ART. METHODS: We recruited a cohort of 88 MSM with AHI in Bangkok, Thailand, who initiated ART immediately. A risk calculator based on viral load and reported behaviour, calibrated to Thai epidemiological data, was applied to estimate the number of onwards transmissions. This was compared with the expected number without early interventions. RESULTS: Forty of the MSM were in 4th-generation AHI stages 1 and 2 (4thG stage 1, HIV nucleic acid testing (NAT)+/4thG immunoassay (IA)-/3rdG IA-; 4thG stage 2, NAT+/4thG IA+/3rdG IA-) while 48 tested positive on third-generation IA but had negative or indeterminate western blot (4thG stage 3). Mean plasma HIV RNA was 5.62 log10 copies/ml. Any condomless sex in the four months preceding the study was reported by 83.7%, but decreased to 21.2% by 24 weeks on ART. After ART, 48/88 (54.6%) attained HIV RNA <50 copies/ml by week 8, increasing to 78/87 (89.7%), and 64/66 (97%) at weeks 24 and 48, respectively. The estimated number of onwards transmissions in the first year of infection would have been 27.3 (95% credible interval: 21.7-35.3) with no intervention, 8.3 (6.4-11.2) with post-diagnosis behaviour change only, 5.9 (4.4-7.9) with viral load reduction only and 3.1 (2.4-4.3) with both. The latter was associated with an 88.7% (83.8-91.1%) reduction in transmission. CONCLUSIONS: Disproportionate HIV transmission occurs during AHI. Diagnosis of AHI with early ART initiation can substantially reduce onwards transmission.

Kazakhstan can achieve ambitious HIV targets despite expected donor withdrawal by combining improved ART procurement mechanisms with allocative and implementation efficiencies.

BACKGROUND: Despite a non-decreasing HIV epidemic, international donors are soon expected to withdraw funding from Kazakhstan. Here we analyze how allocative, implementation, and technical efficiencies could strengthen the national HIV response under assumptions of future budget levels. METHODOLOGY: We used the Optima model to project future scenarios of the HIV epidemic in Kazakhstan that varied in future antiretroviral treatment unit costs and management expenditure-two areas identified for potential cost-reductions. We determined optimal allocations across HIV programs to satisfy either national targets or ambitious targets. For each scenario, we considered two cases of future HIV financing: the 2014 national budget maintained into the future and the 2014 budget without current international investment. FINDINGS: Kazakhstan can achieve its national HIV targets with the current budget by (1) optimally re-allocating resources across programs and (2) either securing a 35% [30%-39%] reduction in antiretroviral treatment drug costs or reducing management costs by 44% [36%-58%] of 2014 levels. Alternatively, a combination of antiretroviral treatment and management cost-reductions could be sufficient. Furthermore, Kazakhstan can achieve ambitious targets of halving new infections and AIDS-related deaths by 2020 compared to 2014 levels by attaining a 67% reduction in antiretroviral treatment costs, a 19% [14%-27%] reduction in management costs, and allocating resources optimally. SIGNIFICANCE: With Kazakhstan facing impending donor withdrawal, it is important for the HIV response to achieve more with available resources. This analysis can help to guide HIV response planners in directing available funding to achieve the greatest yield from investments. The key changes recommended were considered realistic by Kazakhstan country representatives.

Optimizing HIV/AIDS resources in Armenia: increasing ART investment and examining HIV programmes for seasonal migrant labourers.

INTRODUCTION: HIV prevalence is declining in key populations in Armenia including in people who inject drugs (PWID), men who have sex with men, prison inmates, and female sex workers (FSWs); however, prevalence is increasing among Armenians who seasonally migrate to work in countries with higher HIV prevalence, primarily to the Russian Federation. METHODS: We conducted a modelling study using the Optima model to assess the optimal resource allocation to meet targets from the 2013 to 2016 national strategic plan to minimize HIV incidence and AIDS-related deaths by 2020. Demographic, epidemiological, behavioural, and programme cost data from 2000 through 2014 were used to inform the model. The levels of coverage that could be attained among targeted populations with different investments, as well as their expected outcomes, were determined. In the absence of evidence of the efficacy of HIV programmes targeted at seasonal labour migrants, we conducted a sensitivity analysis to determine the cost-effective funding threshold for the seasonal labour migrant programme. RESULTS: The optimization analysis revealed that shifts in funding allocations could further minimize incidence and deaths by 2020 within the available resource envelope. The largest emphasis should be on antiretroviral therapy (ART), with the optimal investment to increase treatment coverage by 40%. Optimal investments also involve increases in opiate substitution therapy and FSW programmes, as well as maintenance of other prevention programmes for PWID and prevention of mother-to-child transmission. Additional funding for these increases should come from budgets for general population programmes. This is projected to avert 17% of new infections and 29% of AIDS-related deaths by 2020 compared to a baseline scenario of maintaining 2013 spending. Our sensitivity analysis demonstrated that, at current spending, coverage of annual testing among migrants of at least 43% should be achieved to warrant continuation of funding for this programme. CONCLUSIONS: Optimization of HIV/AIDS investment in Armenia, with a main priority for scaling-up ART, and less emphasis on primary prevention in the general non-key population could significantly reduce incidence and deaths by 2020.

In the interests of time: improving HIV allocative efficiency modelling via optimal time-varying allocations.

INTRODUCTION: International investment in the response to HIV and AIDS has plateaued and its future level is uncertain. With many countries committed to ending the epidemic, it is essential to allocate available resources efficiently over different response periods to maximize impact. The objective of this study is to propose a technique to determine the optimal allocation of funds over time across a set of HIV programmes to achieve desirable health outcomes. METHODS: We developed a technique to determine the optimal time-varying allocation of funds (1) when the future annual HIV budget is pre-defined and (2) when the total budget over a period is pre-defined, but the year-on-year budget is to be optimally determined. We use this methodology with Optima, an HIV transmission model that uses non-linear relationships between programme spending and associated programmatic outcomes to quantify the expected epidemiological impact of spending. We apply these methods to data collected from Zambia to determine the optimal distribution of resources to fund the right programmes, for the right people, at the right time. RESULTS AND DISCUSSION: Considering realistic implementation and ethical constraints, we estimate that the optimal time-varying redistribution of the 2014 Zambian HIV budget between 2015 and 2025 will lead to a 7.6% (7.3% to 7.8%) decrease in cumulative new HIV infections compared with a baseline scenario where programme allocations remain at 2014 levels. This compares to a 5.1% (4.6% to 5.6%) reduction in new infections using an optimal allocation with constant programme spending that recommends unrealistic programmatic changes. Contrasting priorities for programme funding arise when assessing outcomes for a five-year funding period over 5-, 10- and 20-year time horizons. CONCLUSIONS: Countries increasingly face the need to do more with the resources available. The methodology presented here can aid decision-makers in planning as to when to expand or contract programmes and to which coverage levels to maximize impact.

Scaling up of HIV treatment for men who have sex with men in Bangkok: a modelling and costing study.

BACKGROUND: Despite the high prevalence of HIV in men who have sex with men (MSM) in Bangkok, little investment in HIV prevention for MSM has been made. HIV testing and treatment coverage remains low. Through a pragmatic programme-planning approach, we assess possible service linkage and provision of HIV testing and antiretroviral treatment (ART) to MSM in Bangkok, and the most cost-effective scale-up strategy. METHODS: We obtained epidemiological and service capacity data from the Thai National Health Security Office database for 2011. We surveyed 13 representative medical facilities for detailed operational costs of HIV-related services for sexually active MSM (defined as having sex with men in the past 12 months) in metropolitan Bangkok. We estimated the costs of various ART scale-up scenarios, accounting for geographical accessibility across Bangkok. We used an HIV transmission population-based model to assess the cost-effectiveness of the scenarios. FINDINGS: For present HIV testing (23% [95% CI 17-36] of MSM at high risk in 2011) and ART provision (20% of treatment-eligible MSM at high risk on ART in 2011) to be sustained, a US$73·8 million ($51·0 million to $97·0 million) investment during the next decade would be needed, which would link an extra 43,000 (27,900-58,000) MSM at high risk to HIV testing and 5100 (3500-6700) to ART, achieving an ART coverage of 44% for MSM at high risk in 2022. An additional $55·3 million investment would link an extra 46,700 (30,300-63,200) MSM to HIV testing and 12,600 (8800-16,600) to ART, achieving universal ART coverage of this population by 2022. This increased investment is achievable within present infrastructure capacity. Consequently, an estimated 5100 (3600-6700) HIV-related deaths and 3700 (2600-4900) new infections could be averted in MSM by 2022, corresponding to a 53% reduction in deaths and a 35% reduction in infections from 2012 levels. The expansion would cost an estimated $10,809 (9071-13,274) for each HIV-related death, $14,783 (12,389-17,960) per new infection averted, and $351 (290-424) per disability-adjusted life-year averted. INTERPRETATION: Spare capacity in Bangkok's medical facilities can be used to expand ART access for MSM with large epidemiological benefits. The expansion needs increased funding directed to MSM services, but given the epidemiological trends, is probably cost effective. Our modelling approach and outcomes are likely to be applicable to other settings. FUNDING: World Bank Group and Australian National Health and Medical Research Council.

Estimating the Cost-Effectiveness of HIV Prevention Programmes in Vietnam, 2006-2010: A Modelling Study.

INTRODUCTION: Vietnam has been largely reliant on international support in its HIV response. Over 2006-2010, a total of US$480 million was invested in its HIV programmes, more than 70% of which came from international sources. This study investigates the potential epidemiological impacts of these programmes and their cost-effectiveness. METHODS: We conducted a data synthesis of HIV programming, spending, epidemiological, and clinical outcomes. Counterfactual scenarios were defined based on assumed programme coverage and behaviours had the programmes not been implemented. An epidemiological model, calibrated to reflect the actual epidemiological trends, was used to estimate plausible ranges of programme impacts. The model was then used to estimate the costs per averted infection, death, and disability adjusted life-year (DALY). RESULTS: Based on observed prevalence reductions amongst most population groups, and plausible counterfactuals, modelling suggested that antiretroviral therapy (ART) and prevention programmes over 2006-2010 have averted an estimated 50,600 [95% uncertainty bound: 36,300-68,900] new infections and 42,600 [36,100-54,100] deaths, resulting in 401,600 [312,200-496,300] fewer DALYs across all population groups. HIV programmes in Vietnam have cost an estimated US$1,972 [1,447-2,747], US$2,344 [1,843-2,765], and US$248 [201-319] for each averted infection, death, and DALY, respectively. CONCLUSIONS: Our evaluation suggests that HIV programmes in Vietnam have most likely had benefits that are cost-effective. ART and direct HIV prevention were the most cost-effective interventions in reducing HIV disease burden.

Control of trachoma in Australia: a model based evaluation of current interventions.

BACKGROUND: Australia is the only high-income country in which endemic trachoma persists. In response, the Australian Government has recently invested heavily towards the nationwide control of the disease. METHODOLOGY/PRINCIPAL FINDINGS: A novel simulation model was developed to reflect the trachoma epidemic in Australian Aboriginal communities. The model, which incorporates demographic, migration, mixing, and biological heterogeneities, was used to evaluate recent intervention measures against counterfactual past scenarios, and also to assess the potential impact of a series of hypothesized future intervention measures relative to the current national strategy and intensity. The model simulations indicate that, under the current intervention strategy and intensity, the likelihood of controlling trachoma to less than 5% prevalence among 5-9 year-old children in hyperendemic communities by 2020 is 31% (19%-43%). By shifting intervention priorities such that large increases in the facial cleanliness of children are observed, this likelihood of controlling trachoma in hyperendemic communities is increased to 64% (53%-76%). The most effective intervention strategy incorporated large-scale antibiotic distribution programs whilst attaining ambitious yet feasible screening, treatment, facial cleanliness and housing construction targets. Accordingly, the estimated likelihood of controlling trachoma in these communities is increased to 86% (76%-95%). CONCLUSIONS/SIGNIFICANCE: Maintaining the current intervention strategy and intensity is unlikely to be sufficient to control trachoma across Australia by 2020. However, by shifting the intervention strategy and increasing intensity, the likelihood of controlling trachoma nationwide can be significantly increased.

Optima: A Model for HIV Epidemic Analysis, Program Prioritization, and Resource Optimization.

Optima is a software package for modeling HIV epidemics and interventions that we developed to address practical policy and program problems encountered by funders, governments, health planners, and program implementers. Optima's key feature is its ability to perform resource optimization to meet strategic HIV objectives, including HIV-related financial commitment projections and health economic assessments. Specifically, Optima allows users to choose a set of objectives (such as minimizing new infections, minimizing HIV-related deaths, and/or minimizing long-term financial commitments) and then determine the optimal resource allocation (and thus program coverage levels) for meeting those objectives. These optimizations are based on the following: calibrations to epidemiological data; assumptions about the costs of program implementation and the corresponding coverage levels; and the effects of these programs on clinical, behavioral, and other epidemiological outcomes. Optima is flexible for which population groups (specified by behavioral, epidemiological, and/or geographical factors) and which HIV programs are modeled, the amount of input data used, and the types of outputs generated. Here, we introduce this model and compare it with existing HIV models that have been used previously to inform decisions about HIV program funding and coverage targets. Optima has already been used in more than 20 countries, and there is increasing demand from stakeholders to have a tool that can perform evidence-based HIV epidemic analyses, revise and prioritize national strategies based on available resources, set program coverage targets, amend subnational program implementation plans, and inform the investment strategies of governments and their funding partners.

The cost-effectiveness of harm reduction.

HIV prevalence worldwide among people who inject drugs (PWID) is around 19%. Harm reduction for PWID includes needle-syringe programs (NSPs) and opioid substitution therapy (OST) but often coupled with antiretroviral therapy (ART) for people living with HIV. Numerous studies have examined the effectiveness of each harm reduction strategy. This commentary discusses the evidence of effectiveness of the packages of harm reduction services and their cost-effectiveness with respect to HIV-related outcomes as well as estimate resources required to meet global and regional coverage targets. NSPs have been shown to be safe and very effective in reducing HIV transmission in diverse settings; there are many historical and very recent examples in diverse settings where the absence of, or reduction in, NSPs have resulted in exploding HIV epidemics compared to controlled epidemics with NSP implementation. NSPs are relatively inexpensive to implement and highly cost-effective according to commonly used willingness-to-pay thresholds. There is strong evidence that substitution therapy is effective, reducing the risk of HIV acquisition by 54% on average among PWID. OST is relatively expensive to implement when only HIV outcomes are considered; other societal benefits substantially improve the cost-effectiveness ratios to be highly favourable. Many studies have shown that ART is cost-effective for keeping people alive but there is only weak supportive, but growing evidence, of the additional effectiveness and cost-effectiveness of ART as prevention among PWID. Packages of combined harm reduction approaches are highly likely to be more effective and cost-effective than partial approaches. The coverage of harm reduction programs remains extremely low across the world. The total annual costs of scaling up each of the harm reduction strategies from current coverage levels, by region, to meet WHO guideline coverage targets are high with ART greatest, followed by OST and then NSPs. But scale-up of all three approaches is essential. These interventions can be cost-effective by most thresholds in the short-term and cost-saving in the long-term.