Global HIV Treatment Optimization

Since 2010, Pangaea has been at the forefront of global efforts to improve the quality of HIV treatment – including drugs, delivery systems, and diagnostics – globally for people with HIV, regardless of where they are from. Pangaea’s Treatment Optimization initiative is a partnership of global researchers, health care providers, drug manufacturers, policy makers, funders, and community members from heavily affected regions.
What is HIV treatment optimization?
There are three priorities:

1. Better drug regimens

Taking stock of the current research and development agenda to answer questions, such as can we make drugs that are easier to take and adhere to? Do we know if they work for pregnant women and children? Who should be doing what, who is going to pay for it and who is going to make sure it happens? When can generic manufacturers plan for scale up? And talk to patients—before spending millions on testing and manufacturing – to make sure the regimens will work for them.

Drug optimization revolves around develop drug regimens that are safe, effective, simple, tolerable, durable, universal and affordable. A key challenge is to bringing the highly effective treatment regimens that are available in the industrialized world to the global South. Treatment optimization strategies to achieve a more appropriate target product profile for heavily affected countries include increasing bioavailability, improving the manufacturing process, sourcing less expensive raw materials, and extending the shelf life. ARVs can also be improved by developing supplies chains, limiting clinic stock-outs, working within communities to ensure treatment is destigmatized and effective, decentralizing treatment programs and policies, and incorporating research into delivery implementation

2. Improved service delivery

This means decentralizing care and improving supply chain so that remote clinics have the tests and medicines in stock when patients need them and working within communities so the services are welcoming, effective, and consistent. It also means putting into place policies and programs so that previously ‘unskilled’ health workers can provide their clients with critical medicines and care.

Adapting service delivery towards decentralized, integrated, community-centered approaches is critical to achieving universal access. UNAIDS estimates that more than 95% of HIV care and treatment in Africa is based on traditional clinic models and has called for at least 30% of care to be delivered in out-of-clinic, community settings to support the continued rollout of ART and to reduce cost. The optimization of service delivery is based on the model of differentiated care, a framework which provides treatment tailored to the needs of people rather than a one size fits all clinic model. The differentiated care framework articulates the location and frequency of care for people living with HIV (PLHIV) who are sick and those who are well, what services are provided based on need and the cadre of provider, whether that be a physician, nurse, pharmacist or trained PLHIV. It is envisaged that an undetectable viral load will be a key decision-making tool as stable PLHIV increasingly receive care in the communities where they live. As part of its best practice work, Pangaea will map existing patterns of service delivery in selected focus countries using population-based surveys and track how these change over time with projected increase use of differentiated care models.

3. Access to the latest HIV tests and diagnostics

Remote population areas, poor laboratory infrastructure and lack of technical expertise required to diagnose and monitor patients are some of the most important challenges. Without monitoring tools there is a substantially increased risk of adverse medical and public health consequences. The availability of viral load testing – critical to ensuring treatment is still effective – is especially limited.

The optimization of diagnostics comes at a time of change with the prioritization of viral load for monitoring treatment success and failure and the de-emphasizing of CD4 count measurement for treatment monitoring. Going forward, diagnostics optimization entails learning lessons from the use of viral load for the early infant diagnosis and applying successful models of dried blood spot specimen transport to central labs and return the results to clinics. No point-of-care viral load device yet exists and optimization in the space will involve understanding the right mix of point-of-care devices and central laboratory testing. Pangaea will work with partners to monitor the scale-up of viral load testing, especially as it relates to the rollout of differentiated care described below.

Conference on Antiretroviral Drug Optimization (CADO)

The first CADO was held in 2010, organized by the Clinton Health Access Initiative (CHAI), the John Hopkins University School of Medicine, and the Bill & Melinda Gates Foundation. Its goal was to explore strategies for the reduction of antiretroviral drug costs.

Pangaea hosted the second CADO in 2013 to identify an HIV research agenda for resource-limited settings over the next five-to-ten years, review existing compounds in early development, identify potential novel approaches to reinvigorate first- and second-line regimens, and determine the role of new technologies to improve long-term durability and affordability. These two conferences brought together experts from academia, governments, foundations, the pharmaceutical industry, and community activists to develop a global HIV-treatment research agenda for the coming decade focused on better therapies and how to make them accessible to a broader population of people living with HIV.

In 2015, Pangaea convened a smaller meeting of experts at the Vancouver International AIDS Society (IAS) Conference with the Amsterdam Institute for Global Health and Development (AIGHD), CHAI, and IAS, to prioritize actions and make recommendations to optimize the medium-term future of HIV treatment. The meeting was chaired by Pangaea’s Treatment Optimization Co-Chairs, Dr Tsi Tsi Apollo, Deputy Director for HIV/AIDS and STIs in the Zimbabwe Ministry of Health and Child Care and Dr Andrew Kambugu, Head of Department, Research Program at Infectious Diseases Institute (IDI), Makerere University College of Health Sciences, Kampala.

Pangaea and partners will continue to convene CADOs as necessary in the next 5 years to ensure research into better treatment regimens, monitoring and delivery is scaled up to meet the growing need.

To access a copy of the CADO 1 report please use the link below


Please download full copies of the CADO 2 and Vancouver TO meeting reports

Vancouver July 17-18, 2015

As part of our commitment to working towards global HIV treatment optimization, Pangaea facilitated an expert meeting with AIGHD, CHAI and IAS in Vancouver on July 17-18. The aims of the meeting were to identify gaps in current research and the medium-term agenda on drug development for both first- and second-line therapies appropriate for resource limited countries. The report of the meeting was launched on 22 July at the Vancouver IAS conference and is available here.


Chaired by Dr Tsi Tsi Apollo (Zimbabwe) and Dr Andrew Kambugu (Uganda) Pangaea, AIGHD, Clinton Health Access (CHAI) and the International AIDS Society (IAS) convened an expert meeting to review the progress, gaps and future plans for HIV drug optimization since the second Conference on Antiretroviral Drug Optimization held in 2013. In particular, the perspectives of country implementers, researchers from the North and the South, innovator and generic pharmaceutical companies, community and global normative guideline agencies.

The meeting prioritized key actions that participants considered essential to bringing further to people living with HIV in resource limited settings, effective, tolerable new drugs, formulations and timelines, and how to operationalize these as rapidly as possible. Participants also prioritized recommendations to optimize service delivery as part of the whole treatment optimization package.

The recommendations of this meeting were presented at a formal conference session on treatment optimization during the 2015 IAS conference in Vancouver.

As a key outcome of the meeting, Pangaea reiterated its ongoing commitment to continue monitoring and disseminating progress on all aspects of the treatment optimization agenda, including convening relevant experts where appropriate. In the light of the START and TEMPRANO results, growing global advocacy for treatment for all, the need for significantly increased global and national resources to fund treatment will be needed. In this context, treatment optimization is an even more critical contributor to expanding the scope and quality of long-term HIV treatment.


  • The availability of a limited formulary of antiretrovirals (ARVs) will facilitate optimization of first- line therapy
  • There should be two first-line choices: efavirenz (EFV) or dolutegravir (DTG) paired with tenofovir (tenofovir disoproxil fumarate [TDF] of tenofovir alafenamide fumarate [TAF]) plus emtricatibine or lamivudine (FTC or 3TC, referred interchangeably as XTC).


  • CADO2 recommended that second-line therapy should include boosted darunavir (DRV) as the preferred protease inhibitor. There is a need to identify which booster (ritonavir [RTV] or cobicistat [COBI]) should be prioritized for use in a fixed dose combination.
  • There is a need to clarify the optimal doses of DRV and RTV in a FDC.
  • Potential manufacturers and purchasing agencies need to define volume needs to maximize further opportunities for cost reduction in the manufacturing of DRV.
  • Research into fixed dose combination of DTG and boosted DRV as a key second-line option needs prioritization.
  • Sequencing should be from an EFV-based first line to a boosted DRV plus DTG or recycled nucleosides in second line.
  • Sequencing should be from a DTG-based first-line to a boosted DRV plus two nucleosides in second-line.
  • Research is needed to evaluate if it is feasible for normative guideline agencies to recommend that RTV and cobisistat (COBI) are interchangeable.


  • Treatment optimization means optimization of drugs and service delivery to maximize retention in care.
  • There is a need to incorporate research into improvements in delivery implementation and retention in care into the treatment optimization agenda, particularly as it relates to efficiencies and improvements through “differentiated care” models.
  • The meeting participants called on WHO to clearly articulate what research is needed to make guideline recommendations.


    We have efficacious first-line drugs now and better drugs becoming available, which have the potential for improved tolerability and reduced cost. While a single EFV-based fixed dose combination for almost everybody with HIV has been a remarkable public health achievement, it needs to be rethought based on the data that we currently have available. The concept of a limited formulary of first-line drugs with two choices, either DTG or EFV (at whatever dose is finally decided), paired with TDF and either FTC or 3TC was supported by meeting participants. TDF and TAF were considered interchangeable for this formulary exercise. The limited formulary was thought to be programmatically feasible even as we move to more decentralization and task shifting. A simple algorithm could guide providers in the choice of regimen. The appropriateness of switching from EFV to DTG was discussed. The scale down of stavudine (d4T) was driven by side effects and any possible scale down of EFV does not have the same level of urgency, as millions of people around the world are stable on an EFV-containing regimen. How to potentially switch people from ERFV to DTG is therefore an open question. A possible scenario is that all those who are stable on the EFV could remain on that regimen, those with tolerability issues be switched and those initiating antiretroviral therapy (ART) for the first time could start the DTG (especially those with high CD4 counts and no HIV-related symptoms) who may benefit from the benefit from the better tolerability of DTG.

    In terms of first-line drug optimization, there are three bodies of work around DTG, EFV 400 mg and TAF. Studies are ongoing to examine the efficacy and tolerability of DTG in access markets with a particular focus on its use in pregnancy and HIV/TB coinfection. It was predicted that the cost of DTG would be the same or less than currently available regimens. A study is ongoing to examine the use of EFV 400 mg in pregnancy and funding is needed to study it in HIV/TB coinfection. The group decided it would be important to discuss further with Gilead its development plans for TAF in both the commercial and access markets. Boosted versus unboosted TAF, access to PK/PD data and use of TAF in pregnancy and people with HIV/TB co-infection were highlighted by the group as issues relevant to resource limited settings.

    Second line

    While currently only 5% of people in low- and middle-income countries (LMIC) are on second-line, this will increase as more treatment failure is diagnosed especially as viral load monitoring is rolled out. DRV was approved in the US in 2006 but is still not widely available in LMIC. Reasons include that DRV was registered as a third line drug only in some LMICs and the lack of an FDC, which is expected to change at the beginning of 2016. Approximately 17 LMICs have now filed for DRV approval. The group heard that the science of the superior efficacy and tolerability of DRV over lopinavir (LPV) and atazanavir (ATV) was not reflected in 2013 WHO guidelines, which do not list DRV as a preferred protease inhibitor because of cost. The group called on WHO recommend DRV as the preferred protease inhibitor. The use of RTV and COBI for DRV was discussed. RTV is widely used in LMICs but COBI is not. Formulating a DRV/RTV single tablet is difficult. Even though the dose of RTV is 100mg milligrams the addition of excipients brings the total milligrams closer 500-600 mg tablet, which is too large to swallow. The group called for research is to evaluate if it is feasible for normative guideline agencies to recommend that RTV and COBI are interchangeable. COBI can only be used in once daily regimens and RTV needs to be the booster in pediatric formulations of DRV. A new second-line regimen of DTG plus boosted DRV is in development. In addition to improved tolerability, this regimen simplifies sequencing from two ARV classes in first-line to two new classes in second-line with improved efficacy compared to the current standard of care of recycling nucleosides from first line into second line. DTG has a clear role in both first- and second-line regimens.


    Whatever regimens are used, sequencing within the public health approach requires that first- and second- line be considered as sets of treatment. If a DTG-based regimen is used in first-line, a boosted protease inhibitor plus two nucleosides would be used in second-line. If an EFV-based regimen is used in first-line, second-line would be a boosted protease inhibitor plus DTG.

    Randomized Clinical Trials and Implementation Science

    There are two options in the introduction of a new first line regimen; conduct a randomized clinical trial (RCT) of a DTG-containing regimen versus standard of care in LMICs or to monitor the global population rollout in the same settings. The group favoured the latter. There are programs such as MaxART in Swaziland, the programs of MSF, AMPATH and others that may have the capacity to monitor the efficacy of the new regimen and conduct the necessary pharmacovigilance in these settings.


    Treatment optimization needs to go beyond the optimization of drugs and include the optimization of service delivery and the strengthening of health systems and community systems to accommodate the continuing scale up of ART in an environment of treatment for all those who are ready to start lifelong ART irrespective of this CD4 count. Less than 30% of people diagnosed with HIV infection in resource limited settings navigate the full cascade of care. [Rosen, Mugglin] The delivery of HIV care in the initial rapid scale-up of HIV care and treatment was based on existing clinic-based models, which are common in highly resourced settings and largely undifferentiated for individual needs. A new framework for treatment based on the specific needs of different groups of individuals across the cascade of care is needed. Differentiating the service needs of those who are unwell and those who are stable on ART and where and how those services are delivered is key to maximizing treatment outcomes. Based on consultations with countries and experts, UNAIDS estimates that 95% of HIV service delivery is currently facility based. Further, UNAIDS projects that increasing community-based service delivery to at least 30% of total service delivery will not only reduce costs but, by bringing services closer to the people who need them, improve service uptake and retention in care.

    The meeting and this report were funded by Pangaea. We are enormously grateful to all our supporters who provide unrestricted funding, particularly the Chevron Corporation, who enable us to carry out our work.

    Please download a full copy of the report here.

  • After over a decade of being at the forefront of the Bay Area’s response to the global AIDS epidemic, Pangaea will be holding its first Global Health Leadership Dinner on May 12th 2015 in downtown Oakland’s Rotunda building, with excellent road and BART links.

    We will be honoring the following local and global heroes who have made a significant difference, saving lives and preventing new HIV infections around the world:

    • Dr Peter Piot, Director, London School of Hygiene and Tropical Medicine, and Founding Executive Director of UNAIDS
    • Dr Huma Abbasi, General Manager of Global Health and Medical, Global Health Champion, Chevron
    • Dr Tsi Tsi Appollo, Deputy Director, HIV and TB Program, Ministry of Health and Child Welfare, Zimbabwe
    • Miss Gloria Lockett, Executive Director, California Prostitutes Education Project (CALPEP)

    Since 2011, with funding from the Bill & Melinda Gates Foundation, the Pangaea Global AIDS Foundation has supported the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) to make effective and efficient use of the best available HIV treatment tools; drugs, diagnostic tests and health care delivery systems. A final consultation in the series, held in Washington, DC from May 20-21, 2014, reaffirms the centrality of leadership by the affected communities—in this case men who have sex with men (MSM) who are living with HIV—in responding effectively to AIDS. The meeting was held in close partnership with the Global Forum on MSM & HIV (MSMGF).

    Meeting participants included 30 global MSM leaders, predominantly from lower- and middle- income countries, many of them living with HIV and all of them longstanding experts in HIV among MSM the field. They gathered to inform the programmatic and research agenda on increasing engagement in the HIV treatment cascade for gay men and other MSM in lower- and middle-income countries. This included optimizing provision and mitigating barriers to services, with an emphasis on legally and socially constrained environments and providing evidence of good practice.

    A study led by Dr. Barrot Lambdin of Pangaea has been published in PLoS One. Read below for the abstract and click the link below to access the full text.

    Introduction : Current estimates suggest an HIV prevalence of 42% among people who inject drugs (PWIDs) in Dar es Salaam, while HIV prevalence is estimated to be 8.8% among the general population in the city. To address the HIV epidemic in this population, the government of Tanzania began establishing HIV prevention, treatment and care services including outreach and medication assisted treatment (MAT) for PWIDs in 2010. We assessed gender inequities in utilization of outreach and MAT services and evaluated differences in HIV risk behaviors between female and male PWIDs.

    HIV and drug abuse are serious inter-related health problems around the world. Recent estimates indicate that there are 16 million people who inject drugs (PWID) throughout 148 counties, among which three million (range 0·8—6·6 million) are living with HIV. In most countries, the prevalence of HIV among PWID is higher compared to the general population due injection-related and sexual risk behaviors associated with drug use. Despite increased HIV risk among PWID, harm reduction and HIV prevention programs among this group are limited, especially in resource-constrained countries.

    Supported by the Bill and Melinda Gates Foundation, the consultative meeting on “Optimal Models of Care for People who Inject Drugs” was organized to identify best practices and models of care that provide comprehensive, evidence-based interventions, promote successful linkage to HIV testing, care and treatment, and integrate collaborative TB and HIV services for people who inject drugs. Recommendations from this meeting are intended to inform the World Health Organization’s (WHO) 2014 consolidated treatment guidelines for key populations (KP).

    Our Work in Tanzania

    In the mid-1980s and the early 1990s, East Africa became an important stop along international drug trafficking routes, thereby introducing heroin in the region. In 2009, 40-45 tons of opiates were trafficked into Africa, most entering through the eastern countries by air and sea, and 34 of those tons were consumed in the region, highlighting it only as a transiting hub, but also a place for consumption. Currently, an estimated 533,000 opiate users live in eastern Africa.

    Pangaea is relieved to learn that Dr Paul Semugoma has been released by the South African Ministry of Home Affairs at Oliver Tambo International Airport Johannesburg, and has removed the threat to deport him to his native Uganda where he is at risk of persecution under the country's anti-LGBT legislation. We are enormously grateful to the South African AIDS Council Civil Society Sector, Treatment Access Campaign, Health4Men and other South African, Pan African and international groups for leading the campaign for his release.

    Pangaea is launching a new program to identify and document effective HIV treatment programs across East- ern and Southern Africa emphasizing programs that link the best in medical services with community-based organizations.

    In the November issue of Current Opinion, Charles Flexner (John Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, MD, USA), Ben Plumley (Pangaea, Oakland, CA. USA) and David Ripin (Clinton Health Access Initiative, Boston, MA, USA) provide a comprehensive overview of current activities aimed at optimizing global HIV treatment. HIV treatment optimization is a process intended to enhance the long-term efficacy, adherence, tolerability, safety, convenience, and affordability of combination ART. The ultimate goal of this process is to expand access to well tolerated and effective lifetime treatment to all those in need.

    Budgets for global HIV treatment and prevention in resource-limited settings will continue to be pressured, and, because the need for treatment scale-up is urgent, the emphasis on value for money has become an increasing priority.

    The first CADO in 2010 focused on developing a research agenda to optimize the doses and combinations of existing approved drugs, including through role of process chemistry, and recommended a research development agenda for HIV drug optimization. The conference identified a portfolio of projects with the potential to significantly optimize treatment while achieving major cost reductions. Projects included improvements in process and formulation chemistry and dose reductions as intermediate technologies with an imperative to focus future resources on developing better regimens and formulations.

    The goals and objectives of CADO2 were to identify and facilitate the development of novel, affordable, optimized drug regimens in resource-limited settings, within a public-health approach. CADO2 participants looked further into the future, to review drugs in the development pipeline, and to highlight gaps in drug development programs.  Underpinning the meeting was the commitment to a single global standard for the equitable treatment of everyone, in both resource-rich and resource-poor settings. Potent, durable and affordable drug regimens are needed to sustain the contribution of universal access to HIV treatment to reversing the global AIDS epidemic. 

    The full report is available for download at or by clicking here 


    On Thursday November 29, Secretary of State Hillary Rodham Clinton commemorated World AIDS Day 2012 and unveiled the PEPFAR Blueprint: Creating an AIDS-free Generation that provides a roadmap for how the U.S. government will work to help achieve an AIDS-free generation. Secretary Clinton will be joined by Ambassador Eric P. Goosby, U.S. Global AIDS Coordinator.

    Secretary Clinton was joined by:
    Ambassador Eric P. Goosby, U.S. Global AIDS Coordinator
    Michel Sidibe, UNAIDS Executive Director
    Dr. Nkosazana Dlamini-Zuma, Chairperson of the African Union Commission
    Florence Ngobeni-Allen, Ambassador for the Elizabeth Glaser Pediatric AIDS Foundation

    The PEPFAR Blueprint is available here:

    This month, Pangaea published a paper in a preeminent journal of women’s health, Reproductive Health Matters. This paper summarizes data from Pangaea’s SHAZ! Project, a study working to increase access to HIV services and improve health outcomes for adolescent women living with HIV in Zimbabwe. Findings highlight the complex and critical nature of disclosure of HIV status among this age group to achieve good HIV and reproductive health outcomes. Programs and services must do more to help young women living with HIV negotiate the complexities of disclosure in the context of achieving desired fertility.

    Abstract: In the Shona culture of Zimbabwe, a high regard for childbearing contributes to strong pressures on women to have children. For young women living with HIV, consequently, disclosure of HIV status can be a central strategy to garner support for controlling fertility. This paper reports findings from qualitative interviews with 28 young women aged 16–20 living with HIV in urban Zimbabwe and discusses how these findings can contribute to better policies and programs for this population. Regardless of their current relationship status, interview participants described disclosure as a turning point in romantic partnerships, recounting stressful experiences with major ramifications such as abuse and abandonment on the one hand, and support and love on the other. All but one participant had been in a committed relationship, and most had disclosed to a previous or current partner, with about half of disclosure experiences resulting in adverse reactions. Findings suggest that sexual and reproductive health services must do more to help young women living with HIV negotiate the complexities of disclosure in the context of achieving desired fertility. © 2012 Reproductive Health Matters

    Full article available at:

    Pangaea is launching a new report, “The Leadership of Affected Communities in Delivering HIV Prevention, Testing and Treatment”, with recommendations from two consultations held in Zimbabwe and Thailand organized with the World Health Organization (WHO), UNAIDS, the Zimbabwe Ministry of Health and Child Welfare, and the Asian Network of People Living with HIV (APN+). These recommendations have been presented to WHO for consideration as it develops new consolidated HIV treatment guidelines for release in 2013. The report distills lessons learned from HIV treatment community organizations from over 30 countries.

    What is a Shadow City?

    "A city, municipality or other jurisdictional area that is overshadowed, and thus overpowered by a larger city that is global in nature and possesses more resources such as expertise, enterprise, money, and national government investment."

    — Marsha Martin (2011), Get Screened Oakland, an initiative of the Office of the Mayor of Oakland

    Dr. Barrot Lambdin, Pangaea's Director of Implementation Science, was lead author of  "Local Residents Trained As 'Influence Agents' Most Effective In Persuading African Couples On HIV Counseling And Testing," published in Health Affairs in August of 2011.

    Dr. Barrot Lambdin, Pangaea's Director of Implementation Science, was lead author of  Patient Volume, Human Resource Levels, and Attrition From HIV Treatment Programs in Central Mozambique published in JAIDS in July 2011.

    Lambdin, Barrot H PhD, MPH; Micek, Mark A MD, MPH; Koepsell, Thomas D MD, MPH; Hughes, James P PhD, MS; Sherr, Kenneth PhD, MPH; Pfeiffer, James PhD, MPH; Karagianis, Marina MBChB; Lara, Joseph MPH; Gloyd, Stephen S MD, MPH; Stergachis, Andy PhD, MS

    JAIDS Journal of Acquired Immune Deficiency Syndromes:

    1 July 2011 - Volume 57 - Issue 3 - pp e33-e39

    doi: 10.1097/QAI.0b013e3182167e90

    Implementation and Operational Research: Epidemiology and Prevention

    Full text of article available here.

    Pangaea researchers have led the development of SHAZ! (Shaping the Health of Adolescents in Zimbabwe) – an HIV prevention intervention and research study in Zimbabwe that empowers adolescent female orphans to avoid sexual risk behaviors by improving economic opportunities and linking them to life skills-based HIV education and clinical care. As a resource for others in the field, Pangaea is pleased to be able to make available the SHAZ! Facilitator's Guide.

    Pangaea convened an expert consultation in July 2009 in Cape Town, South Africa on behalf of the Office of AIDS Research (OAR) at the National Institutes of Health (NIH), aimed at addressing the growing imperative for analyses to inform and improve uptake of proven interventions and to scale up HIV/AIDS programs.

    HIV Prevention Among Injection Drug Users: Strengthening U.S. Support for Core Interventions, CSIS Global Health Policy Center, April 2010 

    This report examines data on the burden of HIV among IDUs and access to and receipt of MAT, needle and syringe programs (NSP), and ART services in 14 countries.

    37 million People worldwide are living with HIV (amfAR Statistics 2014: Worldwide)

    16 million Women living with HIV (United Nations Statistics 2014)

    15 million People living with HIV having access to antiretroviral therapy (amfAR Statistics 2014: Worldwide)

    5,600 People Contract HIV every day - more than 230 every hour (amfAR Statistics 2014: Worldwide)