In their recent article in The BMJ (“Is elimination of vertical transmission of HIV in high prevalence settings achievable?”)1 Goga and colleagues make several important points, including that more realistic targets are needed to maintain momentum to reduce vertical transmission of HIV in countries with high prevalence. They also make a constructive proposal to encourage countries to use “dashboards” to track key coverage and process indicators, particularly during the “pre-elimination period,” and to encourage continuous programme assessment and use of data for improvement. We are concerned, however, that they misrepresent the World Health Organization (WHO) and global partners’ elimination of mother-to-child transmission of HIV and syphilis (EMTCT) initiative.2 The authors include a box showing the criteria for elimination of vertical transmission of HIV from the …

WHO has set global targets for the elimination of hepatitis B and hepatitis C as a public health threat by 2030. However, investment in elimination programmes remains low. To help drive political commitment and catalyse domestic and international financing, we have developed a global investment framework for the elimination of hepatitis B and hepatitis C. The global investment framework presented in this Health Policy paper outlines national and international activities that will enable reductions in hepatitis C incidence and mortality, and identifies potential sources of funding and tools to help countries build the economic case for investing in national elimination activities. The goal of this framework is to provide a way for countries, particularly those with minimal resources, to gain the substantial economic benefit and cost savings that come from investing in hepatitis C elimination.

Background The World Health Assembly calls for elimination of viral hepatitis as a public health threat by 2030 (ie, -90% incidence and -65% mortality). However, WHO's 2017 cost projections to achieve health-related Sustainable Development Goals did not include the resources needed for hepatitis testing and treatment. We aimed to estimate the incremental commodity cost of adding scaled up interventions for testing and treatment of hepatitis to WHO's investment scenarios. Methods We added modelled costs for implementing WHO recommended hepatitis testing and treatment to the 2017 WHO cost projections. We quantified additional requirements for diagnostic tests, medicines, health workers' time, and programme support across 67 low-income and middle-income countries, from 2016-30. A progress scenario scaled up interventions and a more ambitious scenario was modelled to reach elimination by 2030. We used 2018 best available prices of diagnostics and generic medicines. We estimated total costs and the additional investment needed over the projection of the 2016 baseline cost. Findings The 67 countries considered included 230 million people living with hepatitis B virus (HBV) and 52 million people living with hepatitis C virus (HCV; 90% and 73% of the world's total, respectively). Under the progress scenario, 3250 million people (2400 million for HBV and 850 million for HCV) would be tested and 58.2 million people (24.1 million for HBV and 34.1 million for HCV) would be treated (total additional cost US$ 27.1 billion). Under the ambitious scenario, 11 631 million people (5502 million for HBV and 6129 million for HCV) would be tested and 93.8 million people (32.2 million for HBV and 61.6 million for HCV) would be treated (total additional cost $58.7 billion), averting 4.5 million premature deaths and leading to a gain of 51.5 million healthy life-years by 2030. However, if affordable HCV medicines remained inaccessible in 13 countries where medicine patents are protected, the additional cost of the ambitious scenario would increase to $118 billion. Hepatitis elimination would account for a 1.5% increase to the WHO ambitious health-care strengthening scenario costs, avert an additional 4.6% premature deaths, and add an additional 9.6% healthy life-years from 2016-30. Interpretation Access to affordable medicines in all countries will be key to reach hepatitis elimination. This study suggests that elimination is feasible in the context of universal health coverage. It points to commodities as key determinants for the overall price tag and to options for cost reduction strategies. Copyright (C) 2019 World Health Organization; licensee Elsevier.

In 2016, the Global Health Sector Strategy (GHSS) on viral hepatitis called for elimination of viral hepatitis as a major public health threat by 2030 (i.e. 90% reduction in incidence and 65% in mortality). In 2017, WHO's first‐ever Global Hepatitis Report presented the baseline values for each of the core indicators of the strategy. We review the challenges and opportunities that lie ahead in order to reach the 2030 service coverage targets.

In 2006, WHO set forth its vision for a public health approach to delivering antiretroviral therapy. This approach has been broadly adopted in resource-poor settings and has provided the foundation for scaling up treatment to over 19·5 million people. There is a global commitment to end the AIDS epidemic as a public health threat by 2030 and, to support this goal, there are opportunities to adapt the public health approach to meet the ensuing challenges. These challenges include the need to improve identification of people with HIV infection through expanded approaches to testing; further simplify and improve treatment and laboratory monitoring; adapt the public health approach to concentrated epidemics; and link HIV testing, treatment, and care to HIV prevention. Implementation of these key public health principles will bring countries closer to the goals of controlling the HIV epidemic and providing universal health coverage.

I hate having AIDS because I will get very sick, and I get very sad when I think of all the other children and babies who are sick with AIDS. I just wish that the government can start giving azidothymidine to pregnant HIV mothers to help stop the virus being passed on to their babies. Nkosi Johnson aged 11 years, Durban, AIDS2000 (Nkosi succumbed to AIDS 6 years later). It is hard to believe that, just 2 decades ago, in most of the world, 1 in 3 babies born to HIV-positive women was HIV-infected, and of those, 1 in 2 died by their second birthday leading to an estimated 5 million children dying of HIV since the beginning of the epidemic. The miracle of antiretroviral therapy (ART) has changed those dismal statistics, not only as direct treatment of adults, adolescents, and children living with HIV infection has kept them alive and from falling ill, but also as universal treatment of women living with HIV infection has prevented transmission of HIV to children prenatally, during birth, or during breastfeeding. Since 1995, an estimated 1.6 million new HIV infections among children have been averted because of the provision of antiretroviral (ARV) medicines to women living with HIV during pregnancy and breastfeeding. Most of these infections (1.3 million) were averted between 2010 and 2015.1 Globally, the annual number of new infections among children (0–14 years) has almost halved since 2010 with a 47% reduction in new HIV cases.2 Despite this significant progress, the number of children becoming newly infected with HIV remains unacceptably high. In 2016, 24% [40%–12%] of pregnant women living with HIV did not have access to ARV medicines to prevent transmission to their infants.3 In the same year, around 160,000 [100,000–220,000] children became infected with HIV.3 In many of the most burdened countries, half of the children exposed to HIV were not tested within the recommended first 2 months of life, and half of the almost 2 million children living with HIV were still not receiving life-saving ART.4 As ART has reached increasing numbers of children, especially from an early age, mortality in perinatally HIV-infected children has declined dramatically, resulting in these children now surviving into adolescence and young adulthood. In addition, 610,000 adolescents (15–24 years) were infected with HIV in 2016, predominantly through sexual transmission, bringing the total number of adolescents living with HIV to 2.1 million.2 Rates of HIV counseling and testing, linkage, and adherence to care and retention in care all remain suboptimal in most regions among adolescent populations. Today, adolescents are the only population group for whom HIV-related mortality continues to increase.5 Early identification, prompt treatment, and effective monitoring and care for infants, children, and adolescents living with HIV can enable them to live long and fulfilling lives. However, a lack of necessary investment, resources and research to optimize testing, pediatric ARV medicines, and adolescent-friendly HIV services mean children and adolescents are in danger of being left behind. For this reason, the undertaking by WHO and the Collaborative Initiative for Pediatric HIV Education and Research (CIPHER) to set a global prioritized research agenda for children and adolescents described in this journal series comes at an excellent time. The methods for this collaborative effort are described by Irvine et al,6 and the recommendations' research priorities for testing, treatment, and care among children and adolescents are described by Penazzato et al7 and Armstrong et al,8 respectively. The important additional ethical and legal requirements for conducting research among the most vulnerable can make such research more challenging and may contribute to children and adolescents living with HIV being left out of the research agenda. Oliveras and coauthors9 point out that this work is not only feasible but recommended if some very basic principles are followed. Getting the work done will need a good mix of innovation, opportunism, and careful design. Sohn and colleagues10 explain how using already existing data, much of it observational, can already teach us much about the best ways to care for these populations. As the number of new perinatal infections continues to decline, innovative designs will be required to test novel treatments and strategies—Ford and colleagues11 examine varied designs that have served to help answer challenging questions in the past and can help us to plan studies more strategically in the future. Clinical trials may not always be feasible or generalizable enough to address all the research questions raised in the collaborative initiative, and Ciaranello12 and Mark and colleagues13 explore the utility of modeling and implementation science, respectively, as additional ways to find answers to these questions. We now have a research agenda laid out, and using the array of methods recommended above, we can fill the gaps in our knowledge that will bring us closer to ensuring that children and adolescents are not left behind. This will require strong political and financial commitment as well as an effective collaboration among key stakeholders, including academic institutions, national governments, community-based organizations, and interested donors. None of us will do this alone, and global platforms such as the one provided by Start Free—Stay Free—AIDS Free can catalyze the attention and the resources to make this happen for children and adolescents worldwide.14

Identifying women living with HIV, initiating them on lifelong antiretroviral treatment (ART), and retaining them in care are among the important challenges facing this generation of health care managers and public health researchers. Implementation research attempts to solve a wide range of implementation problems by trying to understand and work within real-world conditions to find solutions that have a measureable impact on the outcomes of interest. Implementation research is distinct from clinical research in many ways yet demands similar standards of conceptual thinking and discipline to generate robust evidence that can be, to some extent, generalized to inform policy and service delivery. In 2011, the World Health Organization (WHO), with funding from Global Affairs Canada, began support to 6 implementation research projects in Malawi, Nigeria, and Zimbabwe. All focused on evaluating approaches for improving rates of retention in care among pregnant women and mothers living with HIV and ensuring their continuation of ART. This reflected the priority given by ministries of health, program implementers, and researchers in each country to the importance of women living with HIV returning to health facilities for routine care, adherence to ART, and improved health outcomes. Five of the studies were cluster randomized controlled trials, and 1 adopted a matched cohort design. Here, we summarize some of the main findings and key lessons learned. We also consider some of the broader implications, remaining knowledge gaps, and how implementation research is integral to, and essential for, global guideline development and to inform HIV/AIDS strategies.

Although not originally part of the MDGs, HIV treatment has been at the center of global HIV reporting since 2003, marked by achievement of the target of 15 million people receiving treatment before 2015 and 18.2 million (16.1–19.0 million) by mid 2016. Monitoring of treatment has been strengthened with harmonized partner reporting and accountability with regular, annual reports. Beyond treatment numbers, increasingly measures of treatment adherence, retention and outcomes have been reported though with varying quality and completeness. However, with the sustainable development goals (SDGs), monitoring treatment is changing in three important ways. First, treatment monitoring is shifting from numbers to coverage and gaps in a cascade of services to achieve universal access. Secondly, this requires greater emphasis on disaggregated, individual level patient and case monitoring systems, which can better support linkage, retention and chronic, long term care. Thirdly, the prevention, testing and treatment cascade with a clear results chain, links treatment numbers to impact, in terms of reduced viral load, mortality and incidence. This agenda will require a greater contribution of routine impact evaluation alongside monitoring, with treatment seen as part of a cascade of services to ensure impact on mortality and incidence. In conclusion, the shift from monitoring treatment numbers to treatment linked to universal access to prevention, testing and treatment and impact on mortality and incidence, will be critical to monitor, evaluate, and improve HIV programs as part of the SDGs.

Abstract: While the Interagency Task Team on the Prevention and Treatment of HIV Infection in Pregnant Women, Mothers, and Children (IATT) partnership existed before the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan), its reconfiguration was critical to coordinating provision of technical assistance that positively influenced country decision-making and program performance. This article describes how the Global Plan anchored the work of the IATT and, in turn, how the IATT's technical assistance helped to accelerate achievement of the Global Plan targets and milestones. The technical assistance that will be discussed addressed a broad range of priority actions and milestones described in the Global Plan: (1) planning for and implementing Option B+; (2) strengthening monitoring and evaluation systems; (3) translating evidence into action and advocacy; and (4) promoting community engagement. This article also reviews the ongoing challenges and opportunities of providing technical assistance in a rapidly evolving environment that calls for ever more flexible and contextualized responses. The effectiveness of technical assistance facilitated by the IATT was defined by its timeliness, evidence base, and unique global perspective that built on the competencies of its partners and promoted synergies across program areas. Reaching the final goal of eliminating vertical transmission of HIV infection and achieving an AIDS-free generation in countries with the highest HIV burden requires that the IATT partnership and technical assistance remain responsive to country-specific needs while aligning with the current programmatic reality and new global goals such as the Sustainable Development Goals and 90-90-90 targets.

The global community, including the World Health Organization (WHO), has committed to ending the AIDS epidemic and to ensuring that 90% of people living with human immunodeficiency virus (HIV) are diagnosed, 90% start treatment, and 90% achieve and maintain virological suppression. The emergence of HIV drug resistance (HIVDR) as antiretroviral treatment programs expand could preclude the 90-90-90 targets adopted by the United Nations General Assembly at the High-Level Meeting on Ending AIDS from being achieved. The Global Action Plan on HIVDR is a call for collective action grounded on normative guidance providing a standardized and robust approach to monitoring, preventing, and responding to HIVDR over the next 5 years (2017-2021). WHO is committed to supporting country, global, regional, and national partners to implement and monitor the progress of the Global Action Plan. This article outlines the key components of WHO's strategy to tackle HIVDR and the role the organization takes in leading the global response to HIVDR.

Introduction: The remarkable expansion in availability of antiretroviral therapy (ART) over the past two decades has transformed HIV infection into a manageable chronic condition. People with HIV infection now live long and healthy lives on treatment that is simpler, safer and cheaper. According to UNAIDS estimates, the global coverage of ART reached 46% in 2015, resulting in a 26% decrease in annual HIV-related deaths since 2010. Such success has positioned treatment access at the centre of the global HIV response as a way to prevent mortality, morbidity and HIV transmission through a "Treat All'' approach. Continuing expansion of treatment is needed to further reduce HIV-related mortality. This progress with treatment, however, masks a stagnation in the estimated annual number of new HIV infections. Continuing levels of HIV incidence despite treatment scale-up stem from several factors, which should be addressed in order to prevent new infections and decrease the numbers of people requiring treatment in the future.Discussion: ART can only reach those already diagnosed, and although it is unclear what proportion of new infections occur during acute and early infection prior to treatment initiation, phylogenetic studies suggest that it might be substantial. Thus, better testing approaches to reach the 40% of people with undiagnosed HIV infection as early as possible are critical. New approaches to reach men, young people and key populations, where HIV risk is highest and HIV prevention, testing and treatment coverage is lowest, are also needed. Overall coverage of effective prevention interventions remains low, enabling HIV transmission to occur, or time is required to show population-level effects. For example, the full impact of the medical male circumcision intervention will be seen once a larger proportion of men in age cohorts with high incidence are circumcised. Finally, strategically focused pre-exposure prophylaxis interventions have the potential to prevent HIV acquisition among populations at substantial risk, averting treatment costs in coming years.Conclusions: The United Nations (UN) targets to end AIDS include the "90-90-90'' targets for HIV diagnosis, treatment and viral suppression. While 90-90-90 has been widely emphasized and adopted by countries and international funders, the focus thus far has largely been on increasing access to ART - the second "90.'' A similar emphasis on achieving UN HIV prevention targets and adequate funding for meeting these is essential, alongside treatment, in order to reduce population-level incidence and change the trajectory of the HIV epidemic over the long term.

There is a clear convergence toward an overarching strategic use of antiretroviral drugs to prevent human immunodeficiency virus (HIV) infection. Four interventions—immediate antiretroviral therapy (ART) for the infected partner in a serodiscordant couple, preexposure prophylaxis (PrEP), prevention of mother-to-child transmission (PMTCT), and postexposure prophylaxis (PEP)—are all strongly recommended by the World Health Organization as effective ways to prevent HIV infection. For HIV-infected individuals, ART to protect an HIV-uninfected partner and PMTCT are both part of an expanding list of recommendations for starting ART immediately to both treat and prevent HIV infection. For HIV-uninfected individuals, PrEP and PEP are increasingly being seen as related interventions, and there are compelling reasons to consider the provision of PEP as a potential gateway to PrEP. The effectiveness of each of these interventions depends on overcoming barriers to seeking services, adequate community understanding and engagement, high levels of access and uptake of services including HIV testing and counselling, and high levels of adherence.

Currently, access to treatment for HCV is limited, with treatment rates lowest in the more resource-limited countries, including those countries with the highest prevalence. The use of oral DAAs has the potential to provide treatment at scale by offering opportunities to simplify drug regimens, laboratory requirements, and service delivery models. Key desirable characteristics of future HCV treatment regimens include high efficacy, tolerability, pan-genotype activity, short treatment duration, oral therapy, affordability, and availability as fixed-dose combination. Using such a regimen, HCV treatment delivery could be greatly simplified. Treatment could be initiated following confirmation of the presence of viraemia, with an initial assessment of the stage of liver disease. A combination DAA therapy that is safe and effective across genotypes could remove the need for genotyping and intermediary viral load assessments for response-guided therapy and reduce the need for adverse event monitoring. Simpler, safer, shorter therapy will also facilitate simplified service delivery, including task shifting, decentralization, and integration of treatment and care. The opportunity to scale up HCV treatment using such delivery approaches will depend on efforts needed to guarantee that the new DAAs are affordable in low-income settings. This will require the engagement of all stakeholders, ranging from the companies developing these new treatments, WHO and other international organizations, including procurement and funding mechanisms, governments and civil society.

Introduction To successfully implement the 2013 WHO consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection at country level, the implications for national and regional health systems need to be considered and addressed. The guidelines target the entire continuum of care for the HIV-infected individual, and in some cases, their partners, and those with unknown status. The guidelines include not only a more inclusive treatment initiation threshold of CD4+ T-cell count of 500 cells/μl or less for adults and adolescents, treatment for life for pregnant and breastfeeding women (or treatment for the duration of pregnancy and breastfeeding regardless of CD4+ T-cell count), treatment regardless of CD4+ T-cell count for children under 5 years of age, discordant couples, those co-infected with either tuberculosis (TB) or severe hepatitis B virus (HBV), and diversification of effective strategies to reach those with unknown status through couples testing and community-based testing. These changes, if fully enacted, will lead to an increase in treatment eligibility of over 60%, from 17.6 million globally, to 28.6 million globally, with variation in that increase by epidemic type and other epidemiologic factors [1]. However, within these increases in volume, health systems will be serving a healthier mix of patients starting antiretroviral therapy (ART), and greater proportions of pregnant women and children, and sexual partners seeking care together. The increased patient volumes and changes in the composition of those seeking care will require rapid attention to existing care delivery strategies in order to ensure that newly diagnosed individuals are served with the maximum efficiency and effectiveness, and others entering or already within the system under existing guidelines are not harmed. Additionally, to be successful over the long term, health systems and HIV programs will need strengthened adherence-support strategies. Systems of care that may already be stressed need to be further augmented through innovations, and in many cases provided with additional resources in order to become more efficient, resilient, robust and effective. The 'Operations' and 'Service delivery' sections (Chapter 9) of the guidelines address these challenges through recommendations for innovations in the models of service delivery, laboratory diagnostics and treatment delivery in the form of fixed-dose combinations (FDCs) to improve the efficiency, reach and quality of the prevention, care and treatment cascade. There are also potential gains from implementing the guidelines that could accrue to and strengthen health systems and communities, such as a healthier and more productive workforce and fewer new HIV infections, especially in newborns, and HIV-related hospitalizations, and these benefits must also be factored into HIV program and country-level decision-making surrounding adoption and adaptation of the new guidelines [2]. Our objective was to examine the implications of the new guidelines across the continuum of care for each of the elements of national health systems, starting with governance and the role of strategic planning and policy, and including diversification of service delivery models, generation and use of data, healthcare financing, human resource capacity, and supply chains for therapeutic and diagnostic commodities. Governance, strategic planning and policy The progress of discovery and change in the HIV epidemic have demanded a high degree of engagement with evolving evidence, as reflected in part by the 10 guidance documents on antiretroviral drug use issued by WHO since 2000. To date, national governments, with the support of civil society and cooperative partners, have employed a variety of approaches to new guideline adoption. Whereas earlier approaches often focused largely on clinical issues, there is now a need for much broader adoption processes to consider the complex interplay between clinical objectives, operational feasibility, issues related to equity, affordability and health systems capacity. In order to consider, adopt and implement new national guidelines with a broad coalition of support, Ministries of Health must take a strong leadership and governance role. When performed well, the key elements of the process at national level include the following: An inclusive and transparent consultative process that draws upon the best available resources, including program experts and managers, healthcare providers, civil society including people living with HIV, community and faith-based groups, key populations, technical specialists, other relevant government Ministries (e.g. Finance), budget experts and economists, researchers, academics, and health-related professional associations. Assembly, analysis and presentation of relevant clinical, programmatic and financial information. Consideration of guidelines changes in light of broader strategic policy frameworks cross-cutting a broader array of health, human rights and development issues. Clear decision-making mechanisms that allow consideration of competing demands. Clear articulation of roles and responsibility of various partners, in order to ensure accountability and oversight of the processes of change. Ensuring that the case for health in national development, including the potential benefits and risks of potential guidelines changes, is clearly communicated early and often to political leadership and external development partners. The recent process of developing and adopting new guidelines for antiretroviral drug use in pregnant and breastfeeding women in Zambia provides an instructive example of the range of activities needed to ensure that guidelines changes are made with broad stakeholder and health systems support (Fig. 1) [3,4]. National governments and civil society are encouraged to learn lessons from peers, and to participate in WHO's regional guidelines dissemination workshops that are designed to support strong national processes of guidelines change.Fig. 1: The process of changing prevention of mother-to-child transmission (PMTCT) guidelines in Zambia.Diversification and integration of service delivery models to manage patient volumes and improve retention and quality The expansion of HIV testing, care and eligibility for ART will require national governments and partners to consider how best to augment or modify their current health systems to accommodate increased volumes and new categories of patients, and to ensure retention across the care and treatment cascade. There is currently an over-reliance on a limited number service delivery models in many countries. Maximum expansion capacity and quality can be achieved by ensuring that a carefully selected variety of models are put in place and adapted strategically to take account of geography, epidemiology and local needs. Thus, it is an opportune time for governments and funders to focus on previously piloted models that are appropriate for scale-up, and to ensure that the most effective models are scaled up systematically in order to provide substantial complementary capacity to absorb new patients and provide ongoing care. Within the new guidelines, there is an increased emphasis on the importance of expanded national HIV testing and counseling strategies in order to identify 'as many people living with HIV as early as possible after acquiring HIV infection, and link them appropriately and in a timely manner to prevention, care and treatment services'. The reality of most HIV-testing programs in most generalized epidemics is that they have been largely dominated by provider-initiated testing (most typically healthcare provider-initiated), which has been favored because of the ease of linkage to services and for its high yield and cost-effectiveness. However, it often identifies people living with HIV late in the course of HIV disease, in particular, men and adolescents, as well as key populations, who have low utilization of healthcare services. With the guidelines' strong recommendation for community-based HIV testing and counseling with linkage to prevention, care and treatment services, governments should consider systematically expanding a number of approaches tailored for their settings, including mobile, door-to-door, index, campaign, workplace and school-based HIV testing and counseling approaches, and other strategies that ensure the inclusion of underserved groups such as children, adolescents and men. It is also important to recognize that the yield of nonclinic-based testing can be lower and more expensive from a human resource perspective, requiring a careful balance to be struck. For concentrated and low-level epidemics, governments are urged to consider guidelines that reflect WHO's strong recommendation to increase the number and diversity of the facilities in which provider-initiated testing and counseling are available, including sexually transmitted infection clinics, hepatitis and TB sites, antenatal care settings and services for key populations, notably MSM, transgender people, sex workers and people who inject drugs (Fig. 2) [5].Fig. 2: Innovative service delivery models to increase diagnosis and early antiretroviral therapy (ART) initiation among key populations in Indonesia.The capacity of national health systems to absorb the greater numbers of healthier, pregnant and individuals accompanied by partners eligible for treatment will be directly related to the extent to which ART sites are diversified, decentralized (and in some cases integrated into primary care services) and generally expanded. Extending care through different models will also relieve traditional ART sites and higher-level facilities and allow a greater focus on the sickest patients, especially in high-burden generalized epidemics. Models for consideration and rapid scale-up include ART initiation and maintenance for mothers and children in high HIV-prevalence settings integrated into antenatal care, and maternal and child health clinics, and for HIV/TB co-infected individuals into TB clinics, and other approaches that reduce the need of patients to come to clinics through community-based treatment clubs with rotating antiretroviral drug pick-up and home delivery, especially in remote rural areas. A systematic review on the impact of decentralization of ART delivery identified evidence from both randomized controlled trials and observational studies, and found that patients initiated at a hospital and maintained at a health center were more likely to be retained [6]. No difference in attrition was observed between those initiated and maintained on ART at a hospital compared to at a health center. Comparable attrition was observed after 12 months in the two trials in which ART maintenance was in the community [6]. Regions with measurable injection drug use may also consider the new strong recommendation for ART initiation integrated into clinics and sites in which opioid substitution therapy (OST) is provided. In areas with strong general outpatient services, integration of HIV services may yield greater equity with other health services, and may more directly enable HIV's chronic care models to benefit care and management responses to other chronic diseases such as diabetes and hypertension. These integrated sites must also be capacitated with on-site laboratories and referrals with a rapid turnaround for results reporting, especially for viral load, CD4+ T-cell count testing, TB testing and safety laboratories. Tiered laboratory systems must work closely with program leadership to ensure strategic investments in the best technologies for sites providing ART. Intentional analyses should be conducted to balance the convenience of point-of-care (e.g. CD4+ T-cell testing) technologies with the use of centralized high-throughput instruments. With anticipated rapid expansion of demand for viral load testing, it is essential to use internationally acceptable methods to locally validate the use of dry blood spots, as a means of viral load testing, which will allow expansion of this capacity without phlebotomy and cold chain capacity – the imminent availability of point-of-care viral load testing will also strengthen the health system's ability to provide good quality care. It is also critical to close the loop with results reporting via short message service or other secure electronic communication. Existing and new models also need to be chosen in order to intentionally retain patients in care and treatment, and ensure adherence to ART. Structural interventions such as increasing access points and decentralization through community-based models can address some of the most commonly cited reasons for disengagement with care (e.g. transport expenses, overcrowding of vertical sites). At an individual level, substantial evidence has demonstrated the benefits of two-way mobile phone text message systems, and WHO has made a strong recommendation for consideration of this approach [7]. As with numerous other proven methodologies, very few countries have systematically evaluated the needs of various vulnerable groups such as pregnant women, adolescents, key populations and healthy individuals starting ART and systematically taken appropriate packages of cost-effective adherence and retention interventions from the pilot phase, to scale. Generation and use of data for monitoring, evaluation, efficiency and quality improvement National and regional health systems of program monitoring and evaluation are fundamental to public health approaches to HIV prevention, care and treatment, and other chronic illnesses. When they work well, systems of measurement serve to provide actionable data for decision-making, starting with the clinician and service delivery sites, to regional and national program managers, related sectors (e.g. Ministries of Finance), and development partners [8]. Although the HIV response has focused substantial investments on monitoring and evaluation, the nature of the emergency response combined with weak health systems and the sheer volume of chronically ill patients have resulted in greater than expected challenges for many national systems. These challenges have been highlighted in recent studies demonstrating serious gaps in the ability of these systems to report on indicators that meaningfully measure program quality, and a lack of consistent data use at the site and regional levels to improve program quality [9]. With the influx of individuals seeking testing and care, and through sites and models not traditionally reporting on ART use (e.g. community-based antiretroviral drug pick-up and antenatal care sites), there are actions that must be taken coincident with guidelines adoption to ensure effective monitoring and evaluation of program quality. National governments and supportive cooperative partners must redouble efforts to harmonize and strengthen platforms for the regular use of data at multiple levels of the health system to ensure that guidelines changes are implemented as expected and that quality of care and patient outcomes are not compromised. Optimal models include monthly or quarterly meetings convened by the Central Ministry of Health, provincial health offices and development partners (including their implementing partners) to review care and treatment cascade performance at the sub-national and local levels. These processes should be linked to performance against prespecified targets and quality improvement processes that ensure clinical sites regularly review their performance on critical elements of the care and treatment cascade and have flexibility to design affordable solutions to common barriers to quality and access to technical assistance as needed. Refocusing on data use also helps to concentrate attention on the volume and types of indicators being collected and the information systems that underlie data collection. A proliferation of potential indicators over the years has in some cases drawn attention away from those indicators considered highest priority at regional and national levels, and countries are encouraged to select their most critical indicators [harmonized with the Global AIDS Response Progress Reporting (GARPr) process] and ensure adequate performance in collecting the indicator [10]. WHO's early warning indicators for HIV drug resistance represent another system of key performance indicators designed to inform quality improvement of ART services at facility level, with built-in capability for district and national-level aggregation of the results for program management purposes. National governments and development partners also need to ensure information systems are operating sufficiently to allow regular reporting and use of the data. There are numerous open source and proprietary systems in use, although few are fully integrated across the cascade of care and treatment and supported at a national level. WHO is working with numerous countries to improve integration of systems using the 'Three Interlinked Patient Monitoring Systems (3IPMS)' for HIV care/ART, a series of generic tools and guidelines to help countries develop and implement a system that collects patient and population-level outcomes and assesses the impact in an integrated fashion across ART, maternal and child health (MCH)/prevention of mother-to-child transmission (PMTCT), and TB/HIV [11]. In 2014, WHO will release consolidated strategic information guidance that will bring together a globally endorsed minimum set of indicators across the continuum of prevention, treatment and care; these will highlight the key measures of quality HIV programs. With this effort, HIV program managers will have access to the critical indicators within one document, harmonized with other global indicators. When regular data are not sufficient to draw conclusions about specific and important areas of the program, other methods may be employed, including use of representative sampling methodologies to collect more detailed information on critical issues that can herald problems with program quality, and qualitative information, before traditional indicators and targeted implementation science studies to evaluate the success of critical program changes (e.g. studies evaluating outcomes of pregnant women starting ART above CD4+ T-cell count of 350 cells/μl) [12]. Establishing funding needs, diversifying financing models and gaining efficiency The HIV response requires ongoing and detailed attention to financing streams to ensure the sustained availability of funding for effective interventions, and with the right timing. Although the new guidelines will have much greater impact on health and incidence of new infections and have the potential to reduce out-year costs, the upfront costs of their implementation are substantially higher [1]. Ministries of Health and Finance have three critical joint challenges with regards new guideline adoption: to estimate the epidemiological and financial impacts of potential guidelines changes in order to assist with local planning and prioritization, to secure diverse funding streams to support ongoing and planned changes to programs, and to ensure the efficient use of available funds. Estimation of the costs of potential guidelines changes can be accomplished using a variety of models, and some countries have been making these types of projections for years. As described in section 10.8 of the guidelines, the Spectrum suite of models is one of the most commonly used, and its AIDS impact, goals and resource needs models can be used to estimate the impact of guidelines changes on number of deaths, number of infant infections, and the associated marginal costs of changing guidelines or approaches in a variety of epidemic types [13]. Other projection models include the One Health Tool, and models developed by the Clinton Health Access Initiative (CHAI), and US President's Emergency Plan for AIDS Relief (PEPFAR), each with various features and potential advantages [14]. Countries are encouraged to consider that any model is only as good as its ease of use, level of support, and structure; attention must be paid in particular to ensuring the soundness of local epidemiological information, programmatic inputs, and unit costs. Although donor funding has comprised the bulk of funding for the HIV response over the first 10 years of the response in many low and some middle-income countries, leading national governments have begun to increase their share [15]. The ability of the domestic funding in low and middle-income countries to further support the HIV and broader health response will be increasingly important, especially if traditional donor funding continues to plateau. These new guidelines present a singular case for changing the course of the HIV epidemic, and further domestic resource mobilization may be compelled by the idea of 'buying impact,' (e.g. investing more in antiretroviral drugs in the next year may reduce HIV incidence so that future generations are less at risk for infection). These arguments may also be helpful in encouraging the contributions of private sector, innovative financing schemes such as the Pledge Guarantee for Health (PGH), and as motivation for development of national insurance schemes that have the potential to provide a more sustainable tool for the HIV response and general health [16,17]. The African Union has illustrated a commitment to working with member states to increase domestic funding for HIV. Establishing regular methods for reviewing the efficiency by which the healthcare system uses resources to produce key outputs and outcomes will also help to justify and further motivate resource investments. For instance, being able to track the range of expenditures required to provide ART to an individual, or provide an HIV testing and counseling service, by province or region, allows examination of outliers, and for refocusing activities [18]. Development partners have made investments in developing these methods over recent years, and national governments are encouraged to join joint exercises to better understand and direct resource use as the new guidelines are implemented. Ensuring adequate human resource capacity to support evolving service delivery models Shortages of trained personnel to deliver the range of services required to deliver quality healthcare are a chronic bottleneck in many countries. Clinics, in many low and middle-income countries, with thousands of patients, are in some cases staffed by only 1–2 clinical officers and nurses, leading to long wait-times and frustrations for patients and a lack of attention to quality improvement. Fortunately, the new guidelines have streamlined many of the main HIV interventions (e.g. a single first-line recommended regimen, available in one pill once daily for HIV-infected adults), and a focus on ensuring patients start ART before they develop complicated HIV-related illnesses. These 'simplifying' trends will further allow national programs to shift routine care delivery to personnel who require less training and to diversify service delivery models and expand community delivery of treatment. The new guidelines also include recommendations for task shifting ART initiation to trained nonphysician clinicians, and for trained and supervised community health workers to dispense ART between regular clinic visits. South Africa has been a leader in generating the evidence for these recommendations and has successfully leveraged task shifting as a means of increasing the number of sites and providers able to serve HIV-infected individuals (Fig. 3) [19–24].Fig. 3: The effective use of task shifting in South Africa as a means of decentralizing and expanding access to HIV care and treatment.Even as countries rapidly adapt and scale-up new models of delivery, the guidelines changes provide a good opportunity to evaluate the current deployment of various levels of personnel, and to use accepted rapid evaluation tools to assess estimated future requirements. For instance, the CHAI has developed tools that allow national governments to estimate the need for additional healthcare workers based on various guidelines choices. These tools can also help countries to model approaches to distributing and deploying healthcare workers, including laboratory staff [25]. These projections can form the basis for discussions with professional societies, schools of nursing, pharmacy, laboratory and medicine, and training programs for other cadres, including community health workers and peer educators. In order to realize the full potential of the health workforce, including substantial numbers of new types of health workers, governments must commit to regular monitoring of program performance and ongoing support for the development of healthcare workers. It is also important to reform regulatory frameworks to enable state support and recognition for new types of health workers that have proven themselves essential to the HIV response, including peer counselors and community health workers. These cadres with the closest links to communities have often been considered volunteers, but now are increasingly relied upon for long-term delivery of services and must receive compensation or incentives, and opportunities for career growth [26]. Ensuring national supply chains are prepared for the increase in volumes and changes in the mix of commodities Many of the critical interventions outlined in the new guidelines are reliant on a consistent supply of essential commodities. Although national supply chains have improved tremendously in the past 10 years of the global HIV response, especially for antiretroviral drug supplies, there remain serious challenges in ensuring that clinics have adequate stocks [27]. For example, interruptions of rapid test kit supplies at the site level undermine the efficiency and effectiveness of PMTCT, ART, and testing and prevention programs [28]. With more frequent and expanded testing capacity underlying plans for reaching individuals before their CD4+ T-cell count falls below 500 cells/μl (in the case of adult treatment), and rapid expansion of viral load capacity, countries will want to ensure that test kits and related commodities are treated with the same sense of urgency as antiretroviral drugs. Critical activities for the rollout of new guidelines include assessment of the capacity of the infrastructure and human resource capacity for storage, transport and data management of the national supply chain(s) for medicines and diagnostics. Specific considerations need to include decisions on antiretroviral drug selection that maximize the use of fixed-dose formulations in order to ensure adherence and simplify supply chains; the potential for viral load testing to drive up demand for second and possibly third-line regimens; estimated quarterly requirements for additional HIV rapid test kits (and other point of care diagnostic supplies such as point-of-care CD4+ T-cell and TB molecular testing reagent cassettes, and pediatric and adult antiretroviral drug formulations given planned pace of scale-up; assessments of the causes of site-level supply shortages, and targeted deployment of available technical assistance resources; and monthly national reviews of site-level stocks of select commodities, with accountability placed at the highest levels of government and donor agencies. Countries will likely have the greatest success with ensuring regular supplies of key commodities such as HIV rapid test kits, antiretroviral drugs and critical laboratory reagents if their demand projections are regularly updated, communicated to their suppliers (manufacturers or supply agents), and fed into global market surveys. The latter is important because the organizations maintaining them (WHO and the Global Fund to fight AIDS, TB and malaria) work with major donors to forecast the demand for various types of products, which enables the manufacturers to anticipate the demand for their products. In addition, the Coordinated Procurement Planning Initiative uses this information and financial risk assessment to help prevent national-level stock-outs. Reporting of stock-outs by users of health services as well as civil society organizations should be encouraged by national governments to ensure that stock-outs are known as early as possible so that action may be taken. In conclusion, the new WHO consolidated guidelines reflect not only evolving clinical science, but also advances in the science and practice of service delivery and program implementation. The most effective processes of guidelines change are convened by government, and reflect transparent, data-driven, consultative processes in which benefits, risks, and priorities can be weighed by multisectoral partners with a stake in the outcome. It is expected that most countries will determine that there is a need to make investments in the diversification of service delivery models, use and collection of data, development of human resources, and supply chains in order to accommodate increased patient volumes and to maintain quality across the care and treatment cascade. If implemented thoughtfully, and with careful regard for the essential elements of national health systems, the new guidelines could yield substantial impacts for individuals living with HIV and public health. Acknowledgements Conflicts of interest There are no conflicts of interest.

Despite the exponential growth in the literature on modelling and simulation studies of impact and cost-effectiveness in different aspects of healthcare, there is no clear consensus on the appropriate role of modelling in the development of recommendations in clinical guidelines. This is compounded both by the lack of a standardised approach to assess the quality of modelling, and lack of clarity on its positioning within the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method for decision-making in the development of WHO guidelines, that considers both evidence from systematic reviews of randomized clinical trials (RTCs) or observational studies, together with stakeholder values and preferences, resource use, and feasibility issues. In the development of the 2013 WHO Consolidated Guidelines on the use of Antiretroviral drugs for treating and preventing HIV infection, a series of modelling projects were undertaken to inform the recommendations on eligibility criteria for ART initiation, and approaches to monitoring for treatment response. We report our experiences, challenges encountered, and several key considerations to guide the future use of modelling in the development of WHO guidelines. These are: (1) Transparency in the conduct and reporting of model inputs and results; (2) The need for agreed standards for critical appraisal and use of modelling data in healthcare policy making; (3) recognition that modelling of cost-effectiveness is only one component of decision-making in development of WHO recommendations and in priority-setting; (4) The need for closer interaction and an ongoing dialogue between modellers and model end-users or decision-makers; (5) the important role of WHO in convening and facilitating comparative assessment of multiple models; and (6) The need to optimize research and data collection to inform modelling studies.

Up to one in seven people living with HIV are co-infected with hepatitis C virus (HCV) [1], and HCV is now a leading cause of death among people living with HIV in some countries [2]. HCV and HIV have a number of important overlapping challenges. While the vast majority of the estimated 180 million people infected with HCV globally are HIV negative, efforts to control HCV infection can be informed by the experience of the global HIV response. Many of the key challenges for scaling up access to HCV treatment have had to be confronted for HIV, including ensuring access to medicines, developing simplified models of care, scaling up prevention alongside treatment, reaching marginalized populations, overcoming stigma and supporting civil society. The annual cost of HIV treatment initially was around $US10,000 per patient [3], but is now available at around $US120 in some countries, and worldwide almost 13 million persons were receiving ART as of the end of 2013. This price reduction and scale-up was the result of concerted efforts by national governments, international organizations, civil society and the pharmaceutical industry to make quality treatment affordable in resource-limited settings. Today, efforts to scale-up anti-HCV therapy face similar challenges. After decades of poor treatment outcomes using drugs discovered over 40 years ago (ribavirin [4] and interferon [5]), a robust drug development pipeline has begun to deliver a number of safe and highly effective treatments; however, the cost of these drugs is currently too high to allow for widespread treatment scale-up, even in high-income settings [6]. Lack of access to treatment also contributes to the low levels of HCV diagnosis in many settings, a dynamic also seen in the early days of the HIV epidemic where patients and health providers were unmotivated to test for HIV in the absence of treatment [7]. Ensuring affordable access to these new drugs will be a precondition for scaling-up HCV treatment globally. Comprehensive strategies that helped improve access to affordable HIV medicines and diagnostics included voluntary and compulsory licensing, patent-sharing arrangements and improved procurement mechanisms which can, in principle, be replicated for HCV. Pharmaceutical companies, international organizations, procurement and funding mechanisms, national governments and civil society all need to play a part in ensuring access to affordable treatment for HCV. Over the last decade, continuous efforts have been made to simplify HIV treatment regimens, patient monitoring and models of service delivery in order to support increased access to treatment and care in resource-limited settings [8]. Initially, a specialized infectious disease approach was used to manage people living with HIV. Today, in many settings the majority of people receiving antiretroviral therapy are managed by nurses in primary care settings; laboratory and treatment requirements have been reduced to a minimal essential package, and high-quality research has validated the safety of shifting tasks from specialists and doctors to non-physician providers [9]. Responding to HCV at scale will require a similar approach. Pilot programmes in high-income settings have already begun to assess approaches to task shifting and decentralization of HCV care [10,11], and such approaches will be even more important in settings where health resources are scarce. Common routes of HCV transmission include injecting drug use, unsafe medical injections and other invasive procedures, contaminated blood products, and less common routes of transmission include mother-to-child transmission, sexual transmission (particularly among HIV-positive individuals), and non-sterile tattoo or piercing procedures. Most of these are also common routes of transmission for HIV and as such the scale-up of prevention services for HIV can reduce the incidence of HCV infection, and vice versa. Improving access to key prevention interventions is in many countries limited by weak blood safety and infection control systems and policies that restrict access to sterile equipment for drug injecting, tattooing and skin piercing, notably in closed settings such as prisons, along with suboptimal availability of condoms, particularly for sex workers and their clients and men who have sex with men. The increased recognition of HCV as a global infectious disease priority provides an opportunity to improve access to basic prevention interventions that can significantly impact on both HCV and HIV transmission. Several vaccines for both HIV and HCV are under development, but none have elicited a level of efficacy to be able to contribute to prevention efforts. HIV and HCV are both stigmatized infections in many societies. In addition, people who are at heightened risk of becoming infected with either or both of these viruses – people who inject drugs, sex workers, men who have sex with men, HIV-positive individuals, and prisoners – are often among the most marginalized in society, with very limited access to health services. Efforts to reduce HIV incidence and mortality have been most successful in countries that have recognized the need to address stigma and ensure access to services for all. Stigma reduction is therefore another critical area that will benefit both HIV and HCV control activities. One obvious example where improved services for marginalized populations will support reductions in incidence of both HIV and HCV is expanded access to safe injecting equipment and opioid substitution therapy for people who inject drugs. Civil society activism has been critical to lobbying for improved access to affordable treatment, mobilizing and maintaining political action and financial resources against HIV, highlighting gaps in the response to HIV both globally and locally, and protesting against policies that may limit the rights of people living with HIV. Similar activism is already contributing to improved access to treatment and care for people with HCV, including from groups working on HIV. However, much more political and financial support is needed to strengthen the HCV activism movement. HCV is an epidemic of global importance, and only a minority of cases are associated with HIV. Nevertheless, the experience gained in responding to HIV provides important opportunities to improve prevention, treatment and care services for people infected with and affected by HCV, strengthening health information systems and encouraging the uptake of policies and improving access to effective, affordable treatment. At the same time, the recognition of the scale of the HCV epidemic has reinforced the need to strengthen blood and injection safety programmes and to improve cancer screening and management services, also important for HIV responses. Over the coming years, the World Health Organization will work to promote policy and programme synergies in the global and national response against both diseases. The authors have no competing interests to declare. NF wrote the first draft. All authors provided critical input to subsequent drafts and approved the final version.

The government of Canada, through the Department of Foreign Affairs, Trade and Development (DFATD) has supported global efforts to reduce the impact of the HIV pandemic. In 2012, WHO and DFATD launched an implementation research initiative to increase access to interventions that were known to be effective in the prevention of mother-to-child transmission of HIV and to learn how these could be successfully integrated with other essential services for mothers and children. In addition to facilitating the implementation research projects, DFATD and WHO promoted four approaches: (1) Country-specific implementation research prioritization exercises, (2) Ministry of Health involvement, (3) Country-led, innovative, high-quality research, and (4) Leveraging regional networks and learning opportunities. While no single aspect of INSPIRE is unique, the process endeavors to promote and support high-quality, rigorous, locally-led implementation research that will have a substantial impact on the health and survival of HIV-infected women and their children.

A viable market for antiretroviral drugs in low- and middle-income countries is key to the continued scale-up of antiretroviral treatment. We describe the price paid by low- and middle-income countries for 10 first- and 7 second-line adult and paediatric treatment regimens from 2003 to 2012, and compare the price of their finished formulations with the price of their active pharmaceutical ingredients in 2005, 2007, 2010 and 2012. Between 2003 and 2012 the median price of adult first-line treatment regimens per treatment-year decreased from USD499 to USD122, and that of second-line regimens from USD2,934 to USD497. In 2005 adult formulations were sold for a price 170% higher than the cost of their active pharmaceutical ingredients. This margin had decreased to 28% in 2012. Between 2004 and 2013, the price of paediatric treatment per treatment-year decreased from USD585 to USD147 for first-line and from USD763 to USD288 for second-line treatment. In 2005, paediatric treatment regimens were sold at a price 231% higher than the cost of their active pharmaceutical ingredients. This margin remained high and was 195% in 2012. The prices paid for antiretroviral drugs by low- and middle-income countries decreased between 2003 and 2012. Although the margins on their sale decreased, there is likely still space for price reduction, especially for the more recent World Health Organization recommended adult first-line regimens and for paediatric treatment.

The government of Canada, through the Department of Foreign Affairs, Trade and Development (DFATD) has supported global efforts to reduce the impact of the HIV pandemic. In 2012, WHO and DFATD launched an implementation research initiative to increase access to interventions that were known to be effective in the prevention of mother-to-child transmission of HIV and to learn how these could be successfully integrated with other essential services for mothers and children. In addition to facilitating the implementation research projects, DFATD and WHO promoted four approaches: (1) Country-specific implementation research prioritization exercises, (2) Ministry of Health involvement, (3) Country-led, innovative, high-quality research, and (4) Leveraging regional networks and learning opportunities. While no single aspect of INSPIRE is unique, the process endeavors to promote and support high-quality, rigorous, locally-led implementation research that will have a substantial impact on the health and survival of HIV-infected women and their children.