SUMMARY BRIEF: SIX KEY QUESTIONS AND ANSWERS

INTERNAL BRIEFING AND QUESTIONS AND ANSWERS KIT ON THE LAUNCHES OF WHO CONSOLIDATED GUIDELINES ON THE USE OF ANTIRETROVIRAL DRUGS FOR TREATING AND PREVENTING HIV INFECTION, 2013 AND GLOBAL UPDATE ON HIV TREATMENT 2013: RESULTS, IMPACT AND OPPORTUNITIES DRAFT Embargo: Content is strictly embargoed for public or media communication until 30 June 2013 (04:00GMT) Target audience: WHO staff Event: International AIDS Society Conference, June 30 July 3 2013 and HIV launch Objective: This document aims to provide general guidance for WHO staff to respond to queries from partners and media in a coordinated and even manner on key topics. It is not an official document of WHO and is intended for internal briefing purposes only. KEY MESSAGES At the end of 2012, 9.7 million people were receiving antiretroviral therapy (ART) in low- and middleincome countries, representing an additional 1.6 million people on ART as compared with the end of 2011. These new figures will be the main message of the Global HIV Treatment Report, which is being launched on the same day as the guidelines. ART scale-up continues in some of the most challenging settings and poorest communities, despite the global financial crisis, with the most substantial expansion of treatment occurring in sub-saharan Africa, which is also the region with the greatest need. Despite this impressive public health response, huge gaps and disparities in access to ART exist in all regions, particularly affecting children and marginalized populations. Implementation of the 2013 ARV guidelines will make 26 million people living with HIV eligible for ART, leaving a treatment gap of 16 million people. If countries are to close the treatment gap and to achieve the global goal of having 15 million people on ART by 2015 it will be necessary to accelerate ART scale-up efforts, improve the quality of treatment and retain people in care. At the same time there is a need to improve the efficiency and effectiveness of ART services if they are to be sustainable in the long term. Universal coverage of ART cannot be achieved overnight health systems will need to be strengthened to deliver treatment and maintain people in care. The progressive strengthening of systems will enable countries to move beyond the 2015 target to move towards universal coverage. HIV infection has become a chronic, treatable health condition, which requires long-term care, integrated into broader health systems. 1

SUMMARY BRIEF: SIX KEY QUESTIONS AND ANSWERS 1. Why do we need these consolidated guidelines? The new 2013 guidelines aim to translate new evidence and country experiences into clinical, operational and programmatic guidance that can transform the way in which countries use antiretrovirals (ARVs) to enable them achieve universal access targets and universal health coverage, in an efficient and sustainable manner. WHO first produced global guidelines on the use of ARVs for HIV treatment in 2002, followed by guidelines on the use of ARVs for preventing mother-to-child transmission of HIV (PMTCT) in 2004. Since then WHO has produced various ARV-related guidelines with updates every two to three years, most recently in 2010. But different guidelines have been developed for different populations and to address different aspects of HIV infection, risking confusion and conflicting guidance. Since 2010 there has been increasing evidence on both individual clinical benefits and population benefits of earlier antiretroviral therapy (ART). People who initiate ARVs between CD4 cell count of 350-500 cells/mm³ and maintain a suppressed viral load, have improved survival, reduction in HIV associated illnesses, reduced exposure to the inflammatory properties of HIV replication (that is associated with HIV-associated and non-hiv associated cancers, ischaemic heart disease, dementia, premature ageing and other non-communicable diseases). Earlier treatment, with suppressed viral load, is associated with a reduction of onward transmission of HIV to others and can benefit the community and public health in general. Since 2010 there have been substantial new developments, with generation of new evidence on the treatment and prevention benefits of ARVs, emergence of new technologies and approaches to expand and diversify HIV testing, treatment and monitoring, and analysis of country experiences. Of particular note has been increasing evidence of the benefits of starting ART earlier (at a CD4 cell count of 500 cells/mm³ as compared with 300 cells/mm³), with the potential for reducing HIVrelated morbidity and mortality and preventing onward transmission of HIV. Also, t is increasing awareness of the association of HIV infection with a broad range of other health conditions, including various noncommunicable diseases and coinfections (such as viral hepatitis), that alert to the need to better integrate and link programmes to leverage broader health outcomes. 2. What is new, what is different? The new guidelines aim to consolidate existing and new guidance from different, fragmented sources, into one document that covers all aspects of the use of ARVs for HIV treatment and prevention, for different populations, age groups and settings. 2

The guidelines consolidate guidance across a number of dimensions: Age groups and populations: The guidelines address the use of ARV drugs for all age groups and populations. Previous, separate WHO guidelines on using ART among adults and adolescents have now been combined with those for children and for PMTCT, harmonizing ARV regimens and treatment approaches to the extent possible across age groups and populations. Continuum of HIV prevention, diagnosis, care and treatment: Guidance on using ARV drugs is presented within the context of the continuum of HIV-related prevention, treatment and care. In addition to providing recommendations on the clinical use of ARV drugs for treatment, the guidelines address other major aspects of HIV-related care. New and existing guidance: Consolidation has allowed for new recommendations to be harmonized with relevant, existing WHO guidance such that this document provides a one stop information source for HIV programme managers and policy makers. Different health services: Consolidation promotes the consistency of approaches and linkage between settings. Consolidated recommendations help to facilitate linkage and promote consistency of approaches across the various settings in which ARV drugs and related services may be provided, including specialized HIV care, primary care, community-based care, maternal and child health services, TB services and services for people who use drugs. Clinical, operational and programmatic guidance: Consolidation brings together clinical recommendations (what to do) with operational recommendations (how to deliver services) and programmatic guidance (how to decide what, where and how to implement and making allocative decisions) A more systematic approach to guidelines review and development will enable updates to be more timely and comprehensive in the future. Clinical, operational and programmatic implications of new science and emerging country practices will be monitored and reviewed every two years to inform global updates. 3. What are the new recommendations? Key new recommendations promote the earlier initiation on ART, the further simplification of ART regimens, with a single preferred first line regimen for adults, pregnant women, adolescents and older children, which is available in a once-a-day fixed-dose combination pill, and improved monitoring of people on ART. They also promote immediate ART for all children under the age of 5 years and pregnant and breastfeeding women. Key new clinical recommendations include: Earlier initiation of ART for all populations (CD4 500 cells/mm³); Immediate ART for children below 5 years of age; Immediate ART for all pregnant and breastfeeding women (PMTCT options): ART for all pregnant and breastfeeding women with the option to discontinue treatment after the MTCT 3

risk period has ceased for women who do not meet the eligibility criteria (Option B) or lifelong ART in all pregnant and breastfeeding women (Option B+); Harmonization of ART across populations (e.g., adults and pregnant women, B/B+) and age groups (adults, adolescents and older children); and A single, preferred, safer first-line ART regimen (TDF/XTC/EFV) Key operational recommendations include: Use of fixed-dose combination formulations, enabling one-pill a day treatment which is well tolerated and affordable; Improved patient monitoring to support better adherence and detect earlier treatment failure through increased use of viral load monitoring; Strategies to promote ART adherence within different settings and populations; Innovative approaches to service delivery through decentralization and integration of services; Improved use of human resources through task-shifting; and Expansion of HIV testing and counselling approaches through community based testing. 4. What are the challenges on the ground to implement these guidelines? Implementation of the new guidelines will increase the numbers of people eligible for ART, put more demands on health systems and initially increase costs with the transition to more costly ART regimens and patient monitoring approaches. However, the guidelines make recommendations for simplifying ART and improving the efficiency and effectiveness of ARV services to build stronger health and community systems. Increased investments now will guarantee major cost-savings in the future. Increased ART eligibility will mean increased patient numbers and demands on the health system. Human resources: the recommendations to decentralize, integrate and task-shift will require adjustments in the organization of services and changes in human resource policies and investments. Procurement and supply chain management: regimen changes will have to be planned to avoid stock-out and bottlenecks to ensure the secure supply of recommended ARVs and diagnostics. Innovation in diagnostics, specifically point-of-care technologies for CD4 and viral load testing, will have to be proactively pursued and made available in countries. Additional financial investment may need to be made, as patients are moved to more expensive but safer and more effective ART regimens and treatment monitoring approaches. These changes will improve treatment adherence, retain more people in care and minimize the ARV 4

toxicities and emergence of HIV drug resistance all contributing to better patient outcomes and greater impact on HIV mortality and transmission. Increasing ART eligibility poses challenges for ensuring equitable access to treatment. The guidelines prioritize the provision of ART to those individuals who are in greatest need of ART for their own health and promote approaches to reaching those populations most marginalized and underserved. 5. What are the potential implications and impact of implementing the Guidelines? Implementation of the guidelines will save an additional 3 million lives and prevent an additional 3.5 million infections over the next 12 years, while adding only 10% to the overall costs of the HIV response. The 2013 WHO ARV guidelines will increase the potential number of people eligible for ART to an estimated 26 million in 2013 (9 million more people than were eligible under the previous 2010 WHO ART guidelines). The overall cost for a comprehensive global HIV response has been estimated to be around US$ 22-24 billion in 2015 including prevention and treatment programmes. Changing from the 2010 to 2013 guidelines will increase the overall annual cost by around 10%. This additional investment can be deemed very cost effective even in least-developed countries in Africa), according to global criteria one HIV infection averted costs around US$ 6 000. Switching from 2010 to 2013 guidelines and initiating ART earlier will help to save many more lives, and prevent many more HIV infections: between now and 2025 providing ART according to the 2010 guidelines would avert a cumulative total of 9 million deaths, while implementing the 2013 guidelines would avert 12 million deaths, saving an additional 3 million lives, or a 33% increase in deaths prevented. Fully implementing the 2010 ART guidelines would prevent 15.5 million new HIV infections between now and 2015, while implementation of the 2013 recommendations would prevent 19 million new infections, preventing an additional 3.5 million new HIV infections. 6. What will WHO do to support countries in implementing the guidelines? WHO has developed a strategy for disseminating the guidelines to all key partners and to support adaptation and implementation at country level, which involves support provided through WHO country, regional and HQ offices. WHO (HQ, regional and country-level) staff will help countries interpret, adapt, disseminate and implement the new guidelines. 5

Regional workshops and capacity building activities will be undertaken to ensure rapid dissemination of the guidelines through all regions, bringing together clinicians, national programme managers, implementers and development partners. Materials are being developed, including slide-sets and other training materials, to assist with capacity building efforts that can be used by different groups. Intensified technical support and financial assistance is likely to be required by individual countries where ARV needs are great and treatment coverage is low. Opportunities for new or reprogrammed funding can be identified through WHO s financing dialogue with external funders (e.g. the Global Fund or PEPFAR) or through domestic budgets. WHO can facilitate national HIV programme reviews or revisions of national ARV guidelines. WHO will be working with key partners to ensure that the new guidelines are adopted into their programmes, harmonizing approaches across different development partners and technical agencies. For example, WHO has already provided briefings to Global fund staff and the Technical Review Panel, capacity building events are being planned with PEPFAR agencies and opportunities are being identified to disseminate and implement the guidelines through a wide range of civil society networks. The guidelines will be regularly updated to ensure that recommendations are most current and meet countries needs and will enable countries to plan for regular programme reviews. 6

COMPREHENSIVE QUESTIONS AND ANSWERS 1. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection 1.1 What is the evidence base for the new recommendations? Overall, 41 systematic reviews were commissioned as part of these consolidated guidelines and provided the basis for the new recommendations. Evidence supporting earlier initiation (between 350-500) based on mortality and morbidity reduction: oobservational studies These is moderate quality evidence for lower risk of death (13 studies) or progression to AIDS (9 studies) with early ART. The pooled analysis of the observational studies found a consistent decreased risk of death with earlier initiation of ART in 13 studies and a decreased risk of progression to AIDS or death in 9 studies and 3 randomized controlled trials with a low level of heterogeneity, supporting moderate-quality evidence for earlier treatment. A further subgroup analysis showed a reduced risk of mortality with a CD4 threshold for initiating ART of 500 cell/mm 3 Randomized control trials There is low quality evidence for lower risk of progression to AIDS or death with early ART (2 RCTs). In the pooled analysis of two randomized controlled trials there was low-quality evidence supporting ART initiation at higher CD4 thresholds for reducing mortality, disease progression or the combined outcome of death and/or progression and, in one trial, the risk of non-aids defining illnesses. Since treatment in the delayed arm of the SMART trial was initiated when the CD4 count fell below 250 cells/mm 3 (rather than 350 cells/mm 3 ), the quality of the evidence for clinical benefit was graded as low because of imprecision and indirectness. Evidence supporting earlier initiation (between 350-500) based on reduction of HIV transmission risk RCT to examine efficacy of ART in preventing HIV transmission between discordant couples. HIV+ partner had CD4 350-550 cells/µl and was randomized to early vs. delayed ART. Significant HIV prevention benefit a 96% reduction in transmission. 1 genetically linked infection in early ART arm vs. 29 infections in delayed arm. RCT and Observational data 7

There is high to moderate quality evidence that treatment prevents sexual transmission of HIV (1 RCT and observational data). There is high-quality evidence from one randomized controlled trial indicating that earlier ART in a HIV+ sexual partner can markedly reduce the risk of sexual transmission to HIV-negative sexual partners. This is supported by the secondary outcomes of a trial that also found a 92% reduction in HIV sexual transmission from partners with HIV taking ART. 1.2. What are the major differences between 2010 and 2013 treatment recommendations? When to start In the 2013 guidelines, the recommended threshold for ART initiation in adults and adolescents has increased from <350 cells in the 2010 guidelines to all people with HIV and a CD4 count of 500 cells/mm 3 or less, giving priority to initiating ART among those with severe/advanced HIV disease or a CD4 count of 350 cells/mm 3 or less. The 2013 guidelines have also expanded the number of situations where ART initiation is recommended in persons with HIV regardless of CD4 count. These now include persons with: Active TB disease (unchanged from the 2010 guidelines) HBV infection in the presence of severe chronic liver disease (similar to the 2010 guidelines, but the term severe chronic liver disease used instead of chronic active hepatitis) All pregnant or breastfeeding women HIV serodiscordant couples (as in the 2012 Guidance on couples HIV testing and counselling guidelines) Infants and children < 5 years of age Pregnant women The 2010 WHO guidelines recommended lifelong ART for women eligible for treatment (based on the 2010 eligibility criteria of CD4 counts 350 cells/mm 3 or presence of WHO clinical stage 3 or 4 disease). For non-eligible women, there was a choice of two prophylaxis option recommended Options A and B The 2013 guidelines recommend ART in all pregnant and breastfeeding women regardless of CD4 count, and then either continue lifelong (option B+) or stop after the period of MTCT risk (option B). Option A is no longer recommended. Children The 2010 WHO guidelines aligned criteria for ART eligibility for children older than five years with those for adults (that is, treat for WHO clinical stage 3 or 4 disease or CD4 350 cells/mm 3 ), and treating all children infected with HIV younger than two years of age regardless of clinical or immunological status. For children between two and five years of age, it was recommended that those with WHO stage 3 or 4, clinical disease or CD4 <25% or 750 cells/mm 3 be treated. 8

In the 2013 guidelines, the revised recommendations have simplified and expanded treatment in children, to include initiating ART in all children up to five years and increasing the CD4 count threshold for ART initiation to 500 cells/mm³ in children 5 years and older, aligning with the new threshold in adults. What to start 2013 WHO recommendations have reduced the number of preferred first-line regimens to one preferred regimen that can be used across a range of populations (adults, adolescents and children older than three years) and as a single-pill, once-daily ART regimens: TDF + FTC or TDF + 3TC with EFV A LPV/r-based regimen is now recommended as first-line ART for all HIV-infected children younger than three years (36 months) of age, regardless of NNRTI exposure. In 2010, use of LPV/r-based treatment was recommended in all children younger than 24 months of age if previously exposed to NNRTIs. Monitoring Before 2010, WHO guidelines on ART recommended using clinical outcomes and CD4 count for routinely monitoring the response to ARV drugs. In 2010, it was recommended that countries consider phasing in viral load testing to monitor the response to ART. In 2013, Viral load is now strongly recommended as the preferred monitoring approach to diagnose and confirm ARV treatment failure. 1.3. How many countries are already treating all people living with HIV? at CD4 count of 500? How many at 350? Currently, no low- and middle-income country has a policy to test and treat all people infected with HIV, irrespective of CD4 cell count. Modelling studies have examined the impact of such a policy, but the evidence does not yet appear to support a shift to such a policy. However in some high-income countries (such as the USA), ARV is being offered to people recently diagnosed with HIV, regardless of their CD4 counts, depending on their specific situations. In terms of low- and middle-income countries, there are some countries such as Algeria, Argentina, Brazil and Romania have updated policies to initiate ART at CD4 <500 cells/mm3. Most low- and middle-income countries--a total of 89 countries have adopted the 2010 WHO ART recommendations to provide ART for HIV-positive individuals with CD4 <350. Of these, 37 countries are in the African Region. 1.4. Why recommend even earlier treatment, what are the advantages of starting early treatment? 9

There are both individual clinical benefits and population benefits of earlier treatment. People who initiate ARVs between 350-500 CD4 and maintain a suppressed viral load, should have improved survival, reduction in HIV associated illnesses, reduced exposure to the inflammatory properties of HIV viral replication (that is associated with HIV associate and non-hiv associated cancers, CAD, dementia, premature aging etc). Earlier treatment and suppressed viral load is associated with a reduction of onward transmission of HIV to others and can benefit the community and public health in general. WHO recognizes the evidence supporting ART for preventing onward transmission of HIV, and the 2013 guidelines provide several strong recommendations supporting ART at any CD4, notably for serodiscordant couples and pregnant women. Currently, the evidence does not support a global recommendation for initiation at any CD4 in all populations, but through its framework of the strategic use of antiretrovirals for the treatment and prevention of HIV, WHO recognizes and supports country decisions to prioritize certain key populations for earlier initiation of ART as a way to control the epidemic. 1.5. Are the recommended drugs available in countries? Are they more expensive than previous drugs? In fact, the new guidelines do not require new drugs to be introduced in treatment programmes, but state a preference for medicines and formulations which are already available. Examples include the fixed dose combination of tenofovir with lamivudine or emtricitabine and efavirenz, in adults, and the fixed dose combination of abacavir and lamivudine in children. These medicines are available in the market, and we know from the manufacturers that there is enough capacity to produce the active ingredients for the preferred combinations. The main constraint is to convert those active ingredients into finished formulations. There are 4 manufacturers able to supply quality-assured 3-drug combinations (Aurobindo Cipla Gilead/Merck, and Mylan) with an estimated combined production capacity in excess of 5 million packs per month. We were told that they expect to nearly double their capacity by the end of this year. In addition, there are 6 manufacturers for the dual combination of tenofovir and lamivudine, and 2 for the dual combination of tenofovir and emtricitabine, and 5 for efavirenz 600 mg tablets. The production capacity for the regimens is currently well in access of 6 million people on treatment, and increasing. Based on this information, we are confident that all countries should be able to secure access to the most preferred combination products by the end of this year. Regarding affordability of the most preferred and recommended first line regimen [EFV 600 +FTC 200 +TDF 300], its price has decreased from a median price of US$242 to US$163 per patient per year between 2010-2013, and the lowest price in 2013 was in Ethiopia at US$141. The lowest price of the alternative 3 drug formulations with lamivudine in 2013 was US$127 in South Africa. 10

When taken as 2 pills ( [3TC 300 +TDF 300] + EFV 600), the price has decreased to less than 100 USD per year in first quarter of 2013. The lowest price was paid in Myanmar at US$95.7 USD. We believe that price of this regimen will continue to decline as more people will be using it. 1.6. What are the recommendations to countries to transition to ARVs required to implement the 2013 guidelines? WHO works together with partners and national programmes in supporting procurement and supply management efforts for HIV programmes. For implementation of the 2013 guidelines, national programmes should plan and discuss with their suppliers the pace at which increased supplies can be made available. This will require a gradual process of transition and countries should consider a phased program such as: Initiation of new patients on a tenofovir based regimen A transition of patients currently on stavudine regimens to a tenofovir based regimen, in a phased program to enable usage of current stavudine stocks and orders. Transition of patients currently on zidovudine regimens to a tenofovir based regimen, in a phased program to enable usage of current zidovudine stocks and orders and taking into account the speed at which increased deliveries of tenofovir products can be ordered and delivered. 1.7. What is the existing level of phasing out D4T/stavudine in countries? How does WHO envisage countries achieve total phase-out as per new guidelines? Since WHO recommended phasing out D4T in late 2009 a number of countries have made rapid progress in shifting all patients to alternative regimens, including the WHO-preferred tenofovirbased first-line. In 2012, 12 % of people in low- and middle- income countries were still using stavudine-based regimens. However, preliminary data show that the share of stavudine in the procurement of antiretrovirals has dropped to 2% in the first quarter of 2013, and suggest that the majority of people who stop stavudine will be able to switch to tenofovir. 1.8. What are the recommendations on toxicity monitoring, particularly in children and adolescents? The guidelines do not recommend mandatory laboratory monitoring for treatment initiation with TDF in adults. However, such monitoring is advisable for people with renal impairment (estimated glomerular filtration rate at <50 ml/min) and high-risk people (those who are older or have underlying renal disease, long-term diabetes or uncontrolled hypertension concomitant 11

with boosted PIs or nephrotoxic drugs) to detect and limit further progression of renal impairment. Evidence suggests that TDF is associated with modest reduction in renal function and bone mineral density but the clinical significance and real magnitude of these side effects need to be investigated further. In children receiving tenofovir, growth parameters need close monitoring. Despite concerns about EFV use during pregnancy, a recent meta-analysis found no overall increase in the incidence of birth defects for first-trimester EFV exposure compared with other ARV drugs. While the Guidelines Development Group emphasized that better data on birth defects are needed, it felt confident that this potential low risk should be balanced against the strong programmatic advantages and the clinical benefit of EFV in preventing HIV infection in infants and for the mother s health. The guidelines stress the importance of toxicity surveillance systems implemented alongside ART at sentinel sites to provide data to better understand the frequency and clinical relevance of these toxicities. Sensitive issues requiring more investigation include the following: bone, growth and renal toxicity profiles of TDF in children and adolescents adverse events associated with EFV during adolescence, such as central nervous system effects renal and bone toxicity associated with the long term use of tenofovir, and the safety of the use of efavirenz and tenofovir containing regimen during pregnancy and in breastfeeding mothers. WHO is working Pepfar, the U.S. Centers for Disease Control and Prevention, and National Institutes of Health on supporting the establishment of ARV pregnancy registries and birth defect surveillance programmes in Malawi, South Africa and Uganda. Other surveillance programmes have been established in Côte d Ivoire (to monitor tenofovir use), Kenya (to monitor overall drug toxicities in HIV-positive adults and children) Viet Nam (to monitor efavirenz and tenofovir toxicities in people who use ARVs mainly to prevent HIV infection, such as in serodiscordant couples), and Lao PDR (focusing on zidovudine and nevirapine). Data from these and other initiatives will help support improvements in the quality of patient care and help guide future drug regimen choices. 1.9. What are the recommendations for TB/HIV patients? As with the 2010 WHO guidelines, all PLHIV with active TB disease are eligible for HIV irrespective of CD4 cell count or clinical stage. First-line ART regimens for adults and adolescents (tenofovir/3tc or FTC/efavirenz) are compatible with standard TB treatment (containing rifampicin). Persons on protease-containing regimens should switch to a TB treatment regimen 12

containing rifabutin (for adults and adolescents) or need a boosted PI dose (children or adults on second-line PI-containing regimens) or to switch to a 3 NRTI regimen (an option for young children only). 1.10. What are the recommendations on hepatitis? As already in the 2010 guidelines, the 2013 guidelines recommend immediate treatment of Hepatitis B and HIV co-infection with Tenofovir and 3TC/FTC NRTI based regimens irrespective of CD4 count, when severe liver disease is present. For hepatitis C, no specific recommendations are being made. Hepatitis C co-infected individuals should be treated as other adults (i.e. <500CD4) The HIV Department is supporting the Global Hepatitis Programme in the development of hepatitis guidelines which will be completed and launched during the 2 nd half of 2013. The HIV Department will support the Global Hepatitis Programme in developing screening guidance. There are a number of new and very promising Hepatitis C drugs being developed and in the pipeline. WHO will be in a position to modify and develop guidance as these drugs become available for low- and middle-income countries. 1.11. What are the new recommendations concerning HIV prevention? There are no new HIV prevention recommendations in the guidelines. The guidelines outline the currently available menu of evidence-based HIV prevention interventions, including those detailed in recent WHO guidance. 1.12. What are the key recommendations concerning ARV use for prevention? What s the evidence base? WHO recommends the use of ART to prevent HIV transmission in serodiscordant couples, regardless of CD4 (This guidance has been available since April 2012). In the consolidated guidelines, one of the considerations in the recommendation to initiate ART at CD4 <500 included the understanding of the HIV prevention benefits of earlier ART initiation. 1.13. What are the new recommendations on EMTCT? The new 2013 guidelines recommend ART in all pregnant and breastfeeding women regardless of CD4 count, and then either continue lifelong (option B+) or stop after the period of MTCT risk (option B). Option A is no longer recommended. 13

1.14. Will there be any impact of the new recommendations on the Elimination Initiative by 2015? Yes, there is an expected impact of greater uptake of ARVs for pregnant women, through the integration of ART services into maternal child health and antenatal care services and thus an expected reduction in mother to child transmission. Transmission data from countries adopting lifelong ARVs for pregnant women will need to be reviewed to assess the potential impact of triple ARVS on the transmission rates and on the overall outcome of number of paediatric infections after the breastfeeding period ends. 1.15. How are the issues of key populations (MSM, sex workers and people who inject drugs) are addressed in the new guidelines? Despite the recognition that people from key populations are disproportionally affected by HIV, currently the limited available data suggest that there is, generally, inequitable access to ART for all key populations, with lower coverage, late initiation and problems with poor retention in care and in services that meet the comprehensive needs of key populations. The consolidated guidelines therefore focus on recommending earlier initiation of ART (CD4<500) for all populations, including key populations. Although there have been some efforts to increase access to HIV services, including ART, for key populations in all regions, this has been piecemeal to date and there has been insufficient attention to developing services that are acceptable and effective. 1.16. Is WHO abandoning other HIV prevention methods such as microbicides and male circumcision by focusing heavily on the use ARVs? WHO is not neglecting HIV prevention. WHO continues to recognize that HIV prevention and treatment programmes need to be implemented together, tailored to epidemiological context and in particular reflecting the needs of key populations and vulnerable groups. WHO continues to be closely involved with governments and partner organizations to support priority countries in East and southern Africa to scale up male circumcision programmes. WHO has recently prequalified a device for non-surgical male circumcision (PrePex) and the WHO technical working group (TAG) on male circumcision devices will continue to monitor and assess safety, acceptability and efficacy data on devices as their use is scaled up. WHO also prioritises the development of comprehensive evidence based prevention, care and treatment approaches for key populations and works with a wider range of partners including important key population networks to support better access and uptake. Following several trials of pre-exposure prophylaxis (PrEP) showing its efficacy in preventing HIV transmission, WHO 14

released guidelines recommending PrEP demonstration projects to determine the most effective way of delivering PrEP and supporting adherence. Similarly WHO continues to work with partners on microbicides. Currently there is insufficient evidence for WHO to formulate microbicides recommendations but WHO will continue to evaluate new data and review new delivery models, including long-acting formulations. 1.17. What is WHO s current position on HIV vaccines? WHO is closely following the initiatives on development of a HIV vaccine. In partnership with UNAIDS and IAVI, expert meetings has been convened in the last years to establish a research agenda and develop adaptive study designs for HIV vaccine clinical trials to identify more rapidly those with potentially higher efficacy. However, despite some recent developments on this field and promising results of some trials in Thailand and Spain, a ready to use vaccine is still years, if not decades, away. Meanwhile, we must continue our focus on evidence-informed combination prevention programmes that are grounded in human rights. When vaccines are available they must be universally available and affordable. 1.18. What are the key recommendations concerning HIV testing and counselling? The consolidated guidelines recommend supporting a range of community based HIV testing and counselling (HTC) approaches to augment HTC provided in clinical settings. Countries are advised to choose a mixture of HTC methods to provide equitable access to HTC. The guidelines also recommend offering HTC to all adolescents in generalised epidemics and providing acceptable approaches for adolescent key populations. Supporting effective linkage from HTC to prevention, care and treatment is stressed for all populations. 1.19. The guidelines recommend viral load testing, but what is the existing level of access to HIV viral load technology in countries? WHO s 2012 survey on the use of ARVs and diagnostics found that in 57 countries 576 VL and EID equipment were present on average 10 per country. If this equipment were optimally deployed, it should enable access to VL testing on a much greater scale than what we see today. However, 11% of VL equipment was not being used. The main reasons were lack of reagents, failure to install the equipment, equipment breakdown and lack of staff training. And then, average number of tests on per machine was only 11 tests per day. This works out to 0.5 VL test per person on ART per year. That so few tests were done can be explained by the technical 15

complexity of the available technology, geographical factors (the machines tend to be in major cities) and financial factors (often the patients need to pay for the tests themselves and they are expensive from 11 to 35 USD/test). In spite of these constraints, access to viral load is increasing in many countries. South Africa, for example, provides viral load to all patients as the preferred approach to treatment monitoring, and Kenya is expanding viral load testing capacity 40-fold, from fewer than 10 000 tests in 2011 to a projected 400 000 tests in 2013. New point-of-care viral load technologies are anticipated to become available in the next 12 months that will help to further expand viral load capacity, including in rural areas, because technical and training requirements will be much less than with the current technologies. 1.20. WHO s recommending offer of a wide range of testing approaches as communicated in 2012 framework, and self-testing was discussed. Is WHO recommending that patients self-test for HIV? WHO, together with the Liverpool School for Tropical Medicine, and other partners recently held the first global consultation on HIV self-testing. A meeting report is available on the WHO website and WHO will be releasing a policy brief on self-testing later in 2013. Acknowledging that HIV self-testing is becoming increasingly available in many countries and settings, WHO discusses its potential to increase knowledge of HIV status and also outlines possible cautions and implementation models for considerations, as well as identify the future research and policy agenda priorities for HIV self-testing. 1.21 The new recommendations are based on service delivery across the continuum of care; will it mean changes in the ways HIV services are delivered? Of course, adjustments will be needed. For example, to implement the new recommendation to offer ART to all HIV infected women regardless of CD4 for life will require that the provision of ART be included in all sites where antenatal care is provided. And treating more people will require more health care providers, who need to be found and authorized to prescribe and supervise ART - in many countries this will require increased emphasis of task shifting, including to service providers at community level. With expanded access to ART, and as HIV becomes a manageable chronic condition, services need to be organized to provide both chronic and acute care. Chronic care requires integrating and linking related services in order to reduce missed opportunities, and strengthen continuity of care. Chronic care requires planned and scheduled visits, systems for longitudinal patient monitoring/tracking, and broader patient support for improved access, ART adherence and retention in care. 16

Strengthening service delivery across the continuum of care is essential. In several settings, HIV care services for PLHIV who are not yet eligible for ART is not organized, lacks systematic follow up during this period, and routine programme monitoring during pre-art period is lacking. The option for delivery of ART at community level between clinical visits will further bring services closer to the community. Studies show that decentralization of HIV services improves retention in care, and potentially improves access to rural and marginalized communities. Collaboration across national programmes (e.g. HIV, TB, SRH/MCH, drug dependency treatment) is essential for effective implementation of integrated services. 1.22. What are the key operational or programmatic recommendations provided in the guidelines? The main programmatic guidance focuses on the decision making process that should underpin the introduction of the new provisions in the guidelines. The key tenets are that programme managers should do so using an open and transparent process, which involves all relevant stakeholders, including PLWH. The decision should take into account: o the present state of the response, o how health systems need to be strengthened to deal with the increased demand, o ethics and human rights concerns, o cost effectiveness of the proposed interventions, and o how equity can be maximized. 1.23. Is WHO concerned about a greater risk of HIV drug resistance with more people getting exposed to ARV drugs? Increasing exposure to ARVs will increase the selective pressure on the virus population in circulation so, one must anticipate that drug resistance will increase. So, definitely, we recommend that the emergence of HIV Drug Resistance be monitored. However, when effective ARVs are administered as one pill once a day, as recommended in the guidelines, adherence is increased, and the likelihood that resistance emerges is less than when individual drugs are administered as single tablets. The use of fixed dose combinations is one of the explanations why the emergence of drug resistance has not increased in low- and middle- income countries to the level seen in industrialized countries, which until recently had no access to 3-drug fixed dose combination products. So far drug resistance rates in low and middle income countries have progressed to between 3 &and 7 % - when in industrialized countries we are now looking at around 10%. This is less than the up to 15% we saw in the US and Japan a few years ago, when no 3-drug fixed dose combinations were available there (Atripla was introduced in 2006). 17

1.24. What s the drug resistance risk for people who will be taking ARVs for prevention purposes for the first-time? We believe that the strategic use of ARVs will tip the balance in favour of controlling the HIV epidemic. As long as programmes use robust treatment regimens, maximize patient adherence, support retention on ART, guarantee drug supply continuity, and routinely monitor levels of HIV drug resistance, the risk posed by HIV drug resistance can be successfully managed. 1.25. How can WHO improve retention? Besides expanding access to ART, programmes need to prioritize to strengthen linkage to care following an HIV diagnosis and retention in care. Multiple, occasionally context specific issues, may affect retention in care. Reducing the cost of care for patients e.g. by delivering services closer to their home, reducing waiting time at health facilities, peer and community support improve retention in care. Timely initiation of ART, improved quality of care, effective care for late presenters may all contribute in further reducing early mortality following initiation of ART. Strengthening monitoring retention across the continuum of care- from HIV diagnosis to enrolment in care, and during pre-art period and after initiation of ART- is essential. This supports countries to generate information relevant for programme decisions. Interventions to improve linkage to and retention in care requires a more targeted programme evaluation and implementation researches. 18

2. State of the HIV epidemic and findings from Global update on HIV treatment 2013 2.1 What is the latest epidemiology of HIV as of 2012? New country, regional and global estimates for 2012 are being finalized and will be published toward the end of 2013. There were 2.4 million new HIV infections adults and children in low- and middle-income countries globally in 2011. This was 20% fewer than in 2001. In 2011, 1.7 million people died from AIDS-related causes worldwide. This represented a 24% decline in AIDS-related mortality compared with 2005 when 2.3 million deaths occurred. As access to ART increases, the number of people living with HIV is also rising: an estimated 34 million were living with HIV at the end of 2011, 69% of them in sub-saharan Africa. 2.2. Where are we in the global response to HIV? Is HIV over? There have been steady reductions in new HIV infections and AIDS-related deaths in recent years in most regions. Unfortunately, however, the HIV epidemic is far from over as the number of deaths and new infections show. Modelling shows that if we continue the momentum- we can control the epidemic in the midterm: after 2020 the number of people who need treatment will decrease, the number of new infections and AIDS deaths will fall to around 800,000 per year in 2025. 2.3. What are the key pressing concerns in HIV globally? The world has made enormous progress in prevention and treatment, and AIDS related deaths and new infection are going down. Many of the big targets are within reach. The prime challenge is to maintain the momentum, including the political commitment, the financial contributions, and the civil society mobilization. Other health agendas are getting increasing attention, such as maternal, child health or NCDs, and some see HIV as dealt with. Yet, a lot still needs to be done and it is important to realize that HIV can be a driver for many other health issues. At a more technical level, there are still pockets where HIV response has been largely insufficient: in particular, treatment access for children remains woefully insufficient and members of key population groups has much less access to treatment than the general population. 19

2.4. What are the key issues for HIV in Asia and Pacific? In Malaysia? In Asia, more than 5 million people were living with HIV at the end of 2011. There have been modest declines (about 12%) in new HIV infections among children. In Malaysia, new HIV infections have decreased by more than 25% between 2001 and 2011, and AIDS- related deaths decreased by 25-49% over the same period. Malaysia s HIV epidemic is comparatively small and is concentrated largely among people who inject drugs. In that key population group, HIV prevalence as high as 40% has been found in some surveillance studies in urban areas. Some harm reduction programmes are being provided, but coverage of needle- and syringe exchange services is moderate, with 100-200 syringes distributed per injecting drug user per year. However, the country reports high rates of HIV testing in this population group (>75%). 2.5. What are WHO s priorities in HIV? Priorities for WHO are set by our Member States, who has have requested specific support in a number of areas that are defined the Global Health Sector Strategy on HIV/AIDS for 2011-2015. These include: Helping countries make optimal use of antiretroviral both for treatment and prevention, and reach global treatment targets. Provide specific support to extend HIV services to mothers and infants, in support of reaching targets set in the Global Plan to Prevent MTCT and keep mothers alive. Ensure that all populations are included in the treatment scale-up and prevention, in particular the most vulnerable and key populations. Track progress in the HIV response, and help country generate the strategic information they need to identify gaps, bottlenecks and optimise their programmes. 2.6. What s WHO view on HIV cure is it on WHO agenda? WHO is closely following the international initiatives on HIV cure. In the next 5-10 years, there may be important progress towards the development of drugs which a person would take for a short period and which could lead to a sterilizing cure or, if the infection were fully controlled but not eradicated, a functional cure. In the last years, several proofs of concept for this possibility emerged, as the apparent cure held in the Berlin patient, who received a stem-cell bone marrow transplant, the Mississippi baby which is apparently functionally cured after receiving triple ART regimen few hours 20

after birth and the early results of the VISCONTI trial where acute infected treated patients are apparently in remission. All these events are promising, but need further studies. Recently, a global scientific strategy named Towards an HIV Cure was launched by the International AIDS Society, which has convened a group of international experts to develop a roadmap for research towards an HIV cure. This group, headed by the Nobel Prize laureate Prof. Françoise Barré-Sinoussi, and which also includes WHO experts, have identified seven important priority areas for basic, translational and clinical research and maps out a path for future research collaboration and funding opportunities. Currently, the following strategies are being investigated and it is expected that all of these strategies will be more efficient in combination with each other, alongside the use of antiretroviral therapy to at least protect the immune system of patients to prepare them for a cure: Gene therapy Treatment optimization and intensification (eliminate all replication) Reversal of HIV latency (increase virus production) Immune-based therapies (reverse pro-latency signalling) Therapeutic vaccination (to enhance host-control) In the long term, there is a perspective that the treatment optimization (Treatment 2.0) and strategic use of antiretroviral research agendas will align with HIV cure agenda to contribute to bringing the HIV cure as a reality. Meanwhile, WHO will continue to promote early HIV testing and provision of ARVs to all HIV eligible for treatment in a public health approach, and periodically revising the global guidelines. 2.7. How many people are receiving treatment globally? 9.7 million were receiving ART in low- and middle-income countries globally at the end of 2012. This was 1.6 million more people than at the end of 2011 the biggest increase in a single year ever. For a sense of the scale of this achievement, consider that in 2003 only 300 000 people in lowand middle-income countries were receiving ART. 2.8. What are the progress levels in regions? Africa is home to 80% of the global HIV burden and treatment need. In the WHO African Region, more than 7.5 million people were receiving treatment at the end of 2012 versus 6.15 million in 2011 (a mere 50 000 in 2002). 21

In Eastern and Southern Africa, more than 6.3 million people were receiving ART in 2012. Close to 2.2 million of those people were receiving ART in South Africa, which has the largest ART programme in the world. Access to ART increased also in Western and Central Africa, but in most countries in this part of Africa, less than half the people eligible for ART (according to the 2010 WHO treatment guidelines) were receiving it in 2012. In the WHO South-East Asia Region, 938 000 people were receiving ART at the end of 2012, about 100 000 more than in 2011. The increase was largely driven by expansion in India and consolidation of high ART coverage in Thailand. In the Americas, 720 000 people were receiving ART in 2012, 65 000 more than in 2011. In the Western Pacific Region, the number of people receiving ART reached 308 000 at the end of 2012. Progress was achieved also in regions that have been lagging behind. In the European Region, 194 000 people were receiving ART in 2012, almost 50% more than the 137 000 people in 2011. In the Eastern Mediterranean Region the number of people receiving ART rose to 25 100 in 2012, up from 20 300 in 2011. 2.9. What is the progress on ART scale up for children and women? 630 000 children younger than 15 years were receiving ART in low- and middle-income countries at the end of 2012, up from 566 000 in 2011. However, the percentage increase was lower than for adults: 10% versus 20% between 2011 and 2012. A stronger focus on expanding ART for children remains essential, especially in the 22 Global Plan priority countries. The scaling up of services for PMTCT progressed well in 2012, with an estimated more than 900 000 women globally receiving ARV medicines (either ART or prophylaxis, but excluding the outdated, single-dose nevirapine prophylaxis regimen). This was a third more than the number in 2009, the baseline year for the Global Plan. In the 21 African priority countries named in the Global Plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive, more than 65% [56%-73%] of pregnant women living with HIV received ARV medicines for PMTCT in 2012, compared with 59% in 2011 and 48% in 2009. Successful interventions for PMTCT are having an impact in reducing the number of children acquiring HIV infection and therefore also the number of children eligible for ART. In the 21 African priority countries of the Global Plan, which account for about 90% of all pregnant women living with HIV and new HIV infections in children in low and middle-income countries, mother- 22

to-child transmission rates declined overall from an estimated 33% [30-38%] in 2005 to 26% [24-30%] in 2009 and 17% [15-20%] in 2012. However, many women living with HIV who need ART are missing opportunities to start treatment during pregnancy, including in some countries that have a high burden of HIV infection. According to data reported by 16 of the 22 priority countries in the Global Plan, an average 59% of pregnant women living with HIV and eligible for ART were receiving lifelong ART in 2012. 2.10. How about key populations? The overall progress hides some important disparities in access to ART. In all regions, the treatment gains are not reaching enough key populations who face high risk of HIV infection (especially sex workers, people who inject drugs, men who have sex with men and transgender people). These key populations are known to encounter many barriers to accessing health services generally and HIV services specifically. In many parts of the world, they face systematic exclusion along with both social and institutionalized stigma, discrimination and harassment. In addition, sex work, injecting drug use and sex between men are criminalized in many countries, which introduces additional barriers to accessing HIV prevention and treatment services, as countrybased studies have confirmed. Detailed data on ART access for key populations, however, are still very limited, making it difficult to estimate national ART coverage levels for these populations. 2.11. What are the progress levels in countries? Progress in high-burden countries has been good overall, but is highly varied. Based on current trends in their ART programmes, countries can be grouped into three broad categories. The first group includes several countries with a high burden of HIV infection and that already are providing treatment to at least 80% of the people who are eligible for ART. Several other countries are poised to emulate them. Examples include Cambodia, Malawi, South Africa, and Brazil. A second group includes several high-burden countries that have made considerable progress in scaling up treatment but that need to boost the pace and scope of their efforts significantly if they are to reach the 80% coverage target in 2015. Examples include China, India, Ukraine, Peru, Angola, Burkina Faso, Togo, Finally, a third group of countries (including a few that have a high burden of HIV) is well behind schedule and is struggling with serious structural weaknesses in their health and governance 23

systems. This smaller group of countries needs major support to boost their treatment efforts. Examples include DRC, Nigeria, South Sudan, many EMRO countries Regardless of the status of countries in scaling up ART, they all need to step up their efforts to maximize its impact. 2.12. Why regions such as EURO and EMRO are lagging behind in terms of ARV access? The reasons tend to differ from country to country. In general in these regions, large proportions of people eligible for ART belong to hard-to-reach key populations that are at higher risk of HIV infection. These key populations include people who inject drugs, sex workers, and men who have sex with men. Stigma and discrimination, punitive laws and policies, and various forms of harassment tend to discourage key populations from interacting with government services, including health services. HIV services are also not sufficiently tailored for the special needs of these populations. Consequently, access to the first step in the treatment pathway HIV testing and counselling is difficult for most key populations. In addition, the EURO region is one of the only regions where the number of people newly acquiring HIV continues to increase, as does the number of people eligible for ART. The region s scale-up efforts are not keeping pace with this epidemiological trend. 2.13. What are some of the countries are doing much better or much worse than others and why? The ingredients of success vary from country to country. But the progress seen in countries with very large burdens of HIV often has a number of factors in common. Countries have achieved strong political commitment at the highest level for their ART scale ups. They have been able to allocate sufficient funding for their ART scale-ups, drawing on both external support and, increasingly, domestic allocations. Their overall health systems function fairly well, and are being strengthened. They have decentralized ART services to primary health care levels, thus greatly increasing the potential number of people who can access to those services, and making it easier for people to access the services. They have gained access to more affordable ARV medicines and diagnostics They have increased the number of people who take HIV tests and know the results of those tests. They have introduced various innovative methods to retain more patients in the treatment pathway and to strengthen treatment adherence. 24

2.14. Can we achieve the universal access goal/universal health coverage for HIV or 15 by 15? The pace of the ART scale up in recent years indicates that the target of 15 million on ART in 2015 can be reached, but it will take substantial effort and support. At the end of 2012, for example, 1.6 million more people were receiving ART than a year earlier the biggest increase yet in a single year. But such increases are significantly shaped by trends in a few countries with very large numbers of people eligible for, and receiving ART (such as Ethiopia, India, Kenya, Malawi, Mozambique, Nigeria, South Africa, Uganda and Zimbabwe). Whether or not the 15 million target is reached will depend to a large extent on progress made in countries such as those. 2.15. How is the goalpost changing with new guidelines? We hear at least 26 million people will require HIV treatment under new guidelines? The target of having 15 million people on ART by the end of 2015 (as agreed to by UN Member States at the High-Level Meeting in June 2011) has not changed. Countries continue to strive toward that target. At the end of 2012, the estimated need for ART based on WHO 2010 guidelines was 16.7 million people globally. If the new guidelines would be applied globally, this number would increase to 25.9 million. The treatment gap would increase from currently 7 million to 16.2 million. Among these, 9.7 m are adults, 2.6 m children, 0.7 million pregnant women >500, and 3.2 million serodiscordant couples. Of course not all of these 26 million people will be cuing for treatment immediately. For example, in most countries, more than half of the people living with HIV are unaware of their HIV status. Scale-up of treatment will be a process that takes years. If the work maintains the current momentum in scale-up, the global number of people on ART could reach a peak of 24.5 million around the end of the decade. After that, the need for ART will decline (to around 18.5 million in 2050), largely due to the prevention effect of ART and the success of other prevention programmes. 24 million people can be reached by 2021 if the current pace of scale-up is maintained (i.e. increasing the number of people on ART by 1,6 million by year) Countries will have to make individual decisions on how they phase earlier treatment. This will include some prioritization where resources are limited. WHO clearly recommends that the sickest should be prioritized in treatment access. 25

2.16. What does it mean for coverage and for target? So does it mean the countries should change their treatment targets? Isn t it a bit discouraging to have an ever increasing target for HIV treatment, when the world is celebrating a great achievement in this regard? Yes, countries will have to review their treatment guidelines and make decision about starting treatment earlier. This is necessary each time global guidelines change based on new evidence and countries have done the same a number of times in the past (last after updating the guidelines in 2010). Increasing targets does not take away from the great success in scale-up so far, scale-up that has produced tangible reductions in people dying of AIDS and people becoming newly infected. Moving towards earlier treatment will mean further maximising the benefits that ART can offer for treatment and prevention. We have now have the target of increasing treatment access from 9,6 to 15 million in 2 ½ years from now this is a huge challenge and we need to keep focus on this. This target was set to represent 80% of the need for ART estimated at the end of 2015 based on 2010 guidelines. At the same time, it is the right moment to think beyond this timeframe. Evidence supports earlier initiation of treatment. Under the new guidelines almost 4 out of 5 people living with HIV would be eligible for treatment. In thinking about new targets we should get away from expressing progress against the frequently changing number of people in need, and rather look at the percentage of people living with HIV who are on ART. See ANNEX FOR KEY FACTS AND FIGURES FROM THE GLOBAL TREATMENT UPDATE 2013 26

3. Impact and implications of the 2013 ARV guidelines in countries 3.1. Does WHO s new guidance imply that we can treat our way out of the epidemic? No, it does not. The evidence shows that ART can have a massive lifesaving and preventive impact. But it will take more than ART alone to overcome the epidemic. The rapid scaling up of high-impact HIV combination prevention--including ART is the only way in which the epidemic will be overcome. Combination prevention refers to the simultaneous use of proven, complementary behavioural, biomedical and structural prevention interventions. They include ART, promoting voluntary medical male circumcision, consistently and correctly using male and female condoms, along with other proven behavioural and structural interventions. ART is an essential part of combination prevention, without massive ART scale-up we cannot overcome the epidemic but ART scale-up alone will not be sufficient. 3.2. What is the impact of new guidelines for the eligibility number? How many people require ARVs now for prevention and how many for treatment purposes and what will be the impact on people who are eligible under previous guidelines? The 2013 WHO ARV guidelines will increase the potential number of people eligible for ART to an estimated 25.9 million in 2013 (9.2 million more people than were eligible under the previous 2010 WHO treatment guidelines). The distinction between ARVs for prevention and for treatment is increasingly becoming an artificial divide. However, for some people preventive ARV remains most important, for example discordant couples and pregnant women living with HIV and with CD4 counts >500 globally at this point around 3.2 million people. The new guidelines however recommend that people who are sicker and need treatment for own health are given priority. In that sense people who were eligible for ART under 2010 guidelines will be among the priority groups. 3.3. Why the target is elevated while countries are struggling to achieve the 2015 target? The 26 million is the number of people who become eligible for ART under new guidelines, but it s now a new target. Universal access is the UN-agreed target which implies to providing ART to 80% of all eligible people. That number calculated in consideration of new 2013 ARV guidelines would be at about 24.5 million. The past decade s experiences confirm that it is possible to expand access to ART on a scale which initially seemed very unlikely to many observers. The immediate priority is for countries to 27

decide whether and how they will implement the new ART guidelines and to introduce the policy and operational changes that are needed to do so. 3.4. Does the world have the financial and political commitments to deliver ARVs to 26 million people? ART scale-up does not happen overnight, even if all the money was there. Today, in most countries more than half of people living with HIV are not even aware of their HIV status. As countries scale-up, the financial investment will have to increase. However, this is partially compensated for by savings due to a decreasing number of new HIV infections (both due to classical prevention programmes and the prevention effect of treatment). The overall cost for an adequate global HIV response has been estimated to be around USD 22-24 billion in 2015 including prevention and treatment programmes. The change from current to 2013 guidelines will increase this cost by around 10%. But this investment will pay off: Once high coverage under the new guidelines has been reached, annual costs will start to decrease, as will the number of people who need ART. On the other hand, if we don t scale-up and the number of people in need of ART will keep on increasing in the long run and so will the costs. Some say: pay now or pay forever. Maintaining political commitment is a huge challenge, considering all the competing health priorities. What make the HIV response distinct it that we can now predict a clear pathway to controlling the epidemic and reducing the number of people living with HIV, the number of people needed ART, and associated costs. The perspective should give a huge boost to the commitment of countries and politicians to mobilise the resource to finish the job. 3.5. What kind of innovative technologies, drugs, testing tools and other will be needed to implement the guidelines? Notable innovations that will support further expansion of quality ART care include: self-testing, as a way to expand testing opportunities when combined with other approaches; point-of-care CD4 as a way to speed up treatment initiation decisions, particularly at lower levels of the health services; fixed-dose combinations of ART, to improve treatment adherence and simplify drug supply management; and dried blood spots and point-of care technologies to improve access to viral load and early infant diagnosis. 3.6. How much funding will implementing the 2013 guidelines require? 28

Implementing the new guidelines so that about 80% of all people eligible for treatment are receiving it would require about a 10% increase in total annual investment in the global HIV response in 2025. In other words, the entire global HIV response in 2025 would need to increase by 10% over estimated US$ 22-24 billion under the previous guidelines. This additional investment can be deemed very cost effective according to global criteria one QALY saved will cost around 630 USD, and one infection averted around 6 000 USD. These resource needs are projected to level off over time before declining after 2025, a trend that reflects the accumulated prevention benefits of expanding the provision of ART. Greater access to ART will reduce new HIV infections and thereby eventually reduce the number of people eligible for ART. 3.7. How many health workers will it require? Do countries have the capacity, as we hear, disheartening messages from developing countries, regarding health worker shortages? Shortages of trained personnel to deliver the range of services required to deliver quality healthcare is a chronic bottleneck in many low and middle-income countries. Fortunately, the new Guidelines have streamlined many of the main HIV interventions (e.g. a single pill once daily for all HIV-infected pregnant mothers), and if implemented with increased testing will be treating healthier individuals over time. These simplifying trends will allow for: Greater ability to shift routine care delivery to lower level personnel with shorter training times More reliance on patient and community-driven delivery models (per #1 above) that leverage a largely untapped community reservoir of support 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. WHO with partners will need to analyse as the guidelines are implemented the number of health care workers (HCW) needed to implement this guidance. Data from a recent modelling study based on costing from South Africa (Till Burningham) has shown that earlier treatment will increase the number of HCWs available for HIV care and treatment in sub-saharan Africa due to the lifesaving and life-prolonging outcome of HIV treatment for those HCWs who are or could become infected with HIV. 3.8. What will be the overall impact of the guidelines in terms of lives saved/infections prevented? What will be the benefits? 29

Switching from 2010 to 2013 guidelines and initiating ART earlier will help save many more lives, and prevention many more HIV infections. In 2011, 1,7 million people died of HIV related causes in low- and middle-income countries. It is estimated that this number can go down to 1.3 in 2025 if we achieve full implementation of the 2010 guidelines. A switch to 2013 guidelines could bring this number down to 0.8 m. Hence the switch will bring an additional 39% reduction of annual AIDS deaths over and above the 2010 guidelines, and can avoid an additional 3 million HIV related deaths between now and 2025. In 2011, 2.4 million new infections occurred in low- and middle-income countries (2.5 million globally)y, a number that is projected to fall 1,25 million in 2025 based on full implementation of a prevention and treatment package, based on 2010 guidelines. If 2013 guidelines will be implemented, this number will fall to 800,000 new infections per year an additional drop of close to a half. Between 2013 and 2025, the switch from 2010 to 2013 guidelines can avoid a total of around 3.5 million new infections. These estimations are based on the assumption of an 80% reduction probability in HIV transmission for people on ART. 3.9. What are the potential implications on country health systems and budgets? What are the minimum requirements for countries to start implementing the new guidelines? The new Guidelines call for changes in patient volume and patient mix, including, but not limited to: 1. substantially increased overall volume of those eligible for ART, 2. a healthier mix of new patients starting ART, 3. a greater proportion of pregnant women and children starting ART, and 4. Increased numbers of sexual partners seeking care together. The increased patient volumes and changes in the composition of those seeking care as a result of Guidelines changes will require rapid attention to existing systems in order to ensure these newly entering patients are served with the maximum efficiency, others entering or already within the system under existing guidelines are not harmed, and quality of care is maintained or improved. Systems of care that may already be stressed need to be further strengthened and augmented with systems innovations in order to become more resilient, robust and effective. There are also potential gains from implementing the Guidelines that could accrue to and strengthen health systems, such as a healthier and more productive workforce and fewer new HIV infections and HIV-related hospitalizations, and these benefits must also be factored into decision-making. 30

3.10. Who will pay the costs? What s the position of the main HIV funders? Global Fund and PEPFAR? How can national governments be encouraged to make more domestic investments in the implementation of the guidelines? The Global Fund recently calculated the global need for funding the HIV response in countries that are eligible for support, i.e. those most affected by HIV and with severe resource limitation. The estimated need for the HIV response over 3 years is 60 billion USD. The fund alone is striving to raise more than 7 billion USD for HIV (of overall 15 million target for all three diseases) of this amount. 20 billion are projected to come from other international donors, such as PEPFAR. The domestic share has been increasingly rapidly which should be further supported. Domestic funding is expected to be around 25 billion USD. If this projection holds up, the remaining gap would only be 13% of the total, a surmountable gap. 3.11. How many countries have adopted or expressed readiness to adapt these guidelines? The table above outlines the number of countries that have already started to implements or take as policy part of the new guidance. 3.12. Did WHO consult countries and donor agencies funding the HIV treatment initiatives regarding the new guidelines, what are their positions? 31