Lukman Ademola Adepoju, Oyetunji Oyewale, Odekunle Bola Odegbemi, Ifeoluwa Abraham Adeagbo ¡ 5 authors
Over 40 years after the identification of human immunodeficiency virus (HIV), Nigeria remain one of the highest burdens of HIV infections in the world, accounting for almost 10% of new infections in sub-Saharan Africa. Despite significant investments and technical supports from different foreign donors including the United States Presidentâs Emergency Plan for AIDS Relief (PEPFAR), the Global Fund, and bilateral partners. The persistent structural, financial, and programmatic gaps continue to hamper the countryâs HIV response. This assessment of HIV-related interventions in Nigeria examines what has been achieved, what still need to be done, and how to establish a sustainable and domestically owned HIV care. The review summarizes evidence from peer-reviewed literature (2018â2025) and major institutional reports (UNAIDS, NACA, WHO, PEPFAR) to assess five key domains: coverage and access, funding and sustainability, health system strengthening, monitoring and evaluation, and sociocultural barriers. Evidence shows that while substantial progress has been achieved in testing, antiretroviral therapy (ART) coverage, and community-based care, the HIV response remains heavily donor-dependent, urban-centered, and fragmented across vertical program streams. The review concludes that to achieve long-term epidemic control (EC) and universal health coverage (UHC) in Nigeriaâs HIV care and programming with there is a need for domestic financing, health system integration, decentralized service delivery, and data-driven accountability frameworks.
Introduction Over the past two decades, Sub-Saharan Africa has achieved remarkable progress toward the UNAIDS 95-95-95 targets through sustained donor investment, community leadership, and political commitment. However, in early 2025, abrupt funding contractions including the suspension of PEPFAR disbursements by the United States and significant cuts by other major donors, threaten to reverse gains in HIV diagnosis, treatment initiation, and viral suppression. This study examines the potential impact of these funding shifts on the HIV response and explores strategies to sustain progress in a changing financing landscape. Methodology This review employed a structured narrative synthesis approach. A comprehensive search was conducted across peer-reviewed journals, grey literature, and institutional reports published between 2020 and 2025. Databases searched were PubMed, Google Scholar, and institutional repositories of UNAIDS, PEPFAR, USAID, and the Global Fund, using terms such as âHIV/AIDS,â âSub-Saharan Africa,â â95-95-95 targets,â âdonor funding cuts,â and âhealth system resilience.â Of 99 records identified, 15 articles and reports met inclusion criteria. Data were thematically analyzed along the three pillars of the 95-95-95 framework, emphasizing health system resilience, equity, and sustainability. Findings Funding cuts have led to immediate service delivery challenges. HIV testing programs in East and Southern Africa report supply chain interruptions, staff shortages, and reduced outreach, particularly in marginalized communities. ART initiation has slowed due to clinic budget constraints and inadequate safety nets, leading to declines in patient retention and treatment uptake. Viral load monitoring systems are increasingly strained, with insufficient resources for reagents, equipment, and logistics. These disruptions are projected to cause a sixfold increase in new infections and a surge in AIDS-related mortality by 2029 if unaddressed. Furthermore, funding disparities are exacerbating inequities, with countries like Botswana and Eswatini maintaining progress due to better ability to absorb shocks, while conflict-affected and resource-poor regions face greater setbacks. Discussion The donor funding shortfall presents both a crisis and an opportunity. Immediate mitigation requires tapping emergency funds, reprogramming health budgets, and negotiating bridge financing with bilateral and multilateral partners. Long-term sustainability hinges on strengthening domestic resource mobilization through health levies, sin taxes, and diaspora bonds, integrating HIV services into primary healthcare, and scaling digital and community-led service delivery platforms for decentralized adherence support. Geospatial targeting and real-time data systems can optimize resource allocation to emerging hotspots. By fostering regional solidarity and community-driven financing, Sub-Saharan Africa can convert this funding crisis into an opportunity for resilient, locally owned HIV responses that keep the path to ending AIDS within reach.
INTRODUCTION: Faced with the coronavirus disease (COVID-19) pandemic, governments worldwide instituted lockdowns to curtail virus spread. Health facility closures and travel restrictions disrupted access to antiretroviral (ARV) therapy for people living with HIV. This report describes how HIV programs in Indonesia, Laos, Nepal, and Nigeria supported treatment continuation by introducing home delivery of ARVs. METHODS: Staff supporting the programs provided accounts of when and how decisions were taken to support ARV home delivery. They captured programmatic information about home delivery implementation using an intervention documentation tool. The 4 country experiences revealed lessons learned about factors favoring successful expansion of ARV home delivery. RESULTS: Three of the countries relied on existing networks of community health workers for ARV delivery; the fourth country, Indonesia, relied on a private sector courier service. Across the 4 countries, between 19% and 51% of eligible clients were served by home delivery. The experiences showed that ARV home delivery is feasible and acceptable to health service providers, clients, and other stakeholders. Essential to success was rapid mobilization of stakeholders who led the design of the home delivery mechanisms and provided leadership support of the service innovations. Timely service adaptation was made possible by pre-existing differentiated models of care supportive of community-based ARV provision by outreach workers. Home delivery models prioritized protection of client confidentiality and prevention measures for COVID-19. Sustainability of the innovation depends on reinforcement of the commodity management infrastructure and investment in financing mechanisms. CONCLUSION: Home delivery of ARVs is a feasible client-centered approach to be included among the options for decentralized drug distribution. It serves as a measure for expanding access to care both when access to health services is disrupted and under routine circumstances.
Zarni Htun, Yingxi Zhao, Hannah Gilbert, Chunling Lu
BACKGROUND: The Global Fund has been a major funding source for HIV/AIDS programs in Myanmar. In this qualitative study, we aim to understand the impact of Global Fund on national HIV/AIDS response in Myanmar during the era of Millennium Development Goals (MDGs). METHODS: We conducted individual in-depth interviews by recruiting key informants through purposive snowball sampling. The respondents were engaged in the national/subnational response to HIV/AIDS in Myanmar and worked for the United Nations agencies, non-governmental organizations (NGOs), and civil society. Interview questions were organized around the role of Global Fund in strengthening national response to HIV/AIDS in the six building blocks of the Myanmar's health system. Transcripts from the key informants were synthesized into specific themes through a deductive approach. RESULTS: We found that the Global Fund has provided substantial support to (1) finance the national HIV/AIDS response in Myanmar, and (2) strengthen leadership and governance at the central level through improving coordination and collaboration, including more stakeholders (e.g. civil society, NGOs) in decision making process, and catalyzing policy changes on scaling-up key interventions. Yet, its role remains limited in addressing new demands at the township level in terms of capacity building, staffing, and medical supply resulting from rapid scale-up of HIV interventions and decentralization of service delivery in the public sector. CONCLUSION: There was a missed opportunity for Myanmar to capitalize on the use of the Global Fund's funding to strengthen the health system. Deliberate planning is required to optimize the use of those scarce resources to provide universal coverage for HIV/AIDS.
Ha Nguyen Thi Thu, Ha Nguyen Thi Thu, Anh Quynh Nguyen, Phuong Nguyen ¡ 7 authors
Objectives: To examine the financing trend for HIV/AIDS programme for 2011â2019 and to explore the potential options to fill funding gap and sustain the programme.Methods: Using mixed methods, including literature review and qualitative interview (16 in-depth interviews with key informants from the Ministry of Health, Ministry of Planning and Investment, Vietnam Authority of HIV/AIDS Control and related departments of Bac Ninh and Dien Bien Provinces).Results: The total fund for 2011â2019 was 22,243 billion VND (USD317.3 million) with the largest contribution of external funding (67%). The share of government budget remains quite low (9%). HIV/AIDS programme is focusing on shifting the finance of HIV/AIDS services from programme/projects to the health insurance fund; increasing the contribution of local government budget and diversifying other domestic sources. It is important for the programme to promote the integration of HIV/AIDS services into the current healthcare system and decentralization of HIV/AIDS services into primary healthcare facilities.Conclusion: To fill the funding gap for HIV/AIDS programme, it requires increasing contribution from local goverment budget for prevention activies as well as social health insurance for treatment. Lessons learnt from HIV/AIDS programme could suggest for other priority public health programmes to sustain their achievements in the upcoming years.
Tyler B. Wray, Philip A. Chan, Erik M. Simpanen, Don Operario
BACKGROUND: Men who have sex with men (MSM) are the group at highest risk for contracting human immunodeficiency virus (HIV) in the United States, but many do not test as frequently as recommended. Home-based self-testing (HBST) for HIV holds promise for promoting regular testing among these individuals, but currently available HBSTs have limited follow-up options, providing only a 1-800 number that participants can call. Failure to actively conduct follow-up counseling and referrals after HBST use could result in delays in seeking confirmatory testing and care among users receiving reactive (preliminary positive) test results. HBST also fails to connect users who test negative with other prevention services that can reduce their future risk for HIV. OBJECTIVE: The aim of our study was to use qualitative research methods with high-risk MSM to inform development of a "smart" HBST kit. The kit utilizes existing Internet-of-Things (IoT) technologies to monitor HBST use in real-time and enable delivery of timely, active follow-up counseling and referrals over the phone. METHODS: In phase 1, individual interviews (n=10) explored how participants might use HBST and their views and preferences for conducting counseling and referral after HBST. Based on these perspectives, we developed a smartphone app (iOS, Android) that uses data from light sensors on Bluetooth low energy (BLE) beacons to monitor when HBST kits are opened, facilitating timely follow-up phone contact with users. In phase 2, a usability study conducted among high-risk MSM (n=10) examined the acceptability and feasibility of this system and provided user perspectives after using the system along with HBST. RESULTS: Phase 1 themes suggested that MSM preferred HBST, that most thought active follow-up after HBST would be valuable, and that doing so over the phone within 24 h after testing was preferable. Phase 2 results showed that the eTEST system successfully detected HBST use in nearly all cases. Participant perspectives also suggested that the timing, method (ie, phone call), and duration of follow-up were appropriate and helpful. CONCLUSIONS: Using BLE beacons and a smartphone app to enable follow-up counseling and referral over the phone after HBST use is feasible and acceptable to high-risk MSM. Future research is needed to compare the effects of follow-up counseling on rates of repeat testing and receipt of referral services (eg, testing for sexually transmitted infections and initiation of preexposure prophylaxis) and to explore the acceptability of the eTEST system over longer periods of time.
Obinna Ositadimma Oleribe, Olabisi Oladipo, Iheaka Paul Ezieme, Mary Margaret Elizabeth ¡ 5 authors
Access to quality care is essential for improved health outcomes. Decentralization improves access to healthcare services at lower levels of care, but it does not dismantle structural, funding and programming restrictions to access, resulting in inequity and inequality in population health. Unlike decentralization, Commonization Model of care reduces health inequalities and inequity, dismantles structural, funding and other program related obstacles to population health. Excellence and Friends Management Care Center (EFMC) using Commonization Model (CM), fully integrated HIV services into core health services in 121 supported facilities. This initiative improved access to care, treatment, support services, reduced stigmatization/discrimination, and improved uptake of HTC. We call on governments to adequately finance CM for health systems restructuring towards better health outcomes.
Philippa Easterbrook, Cadi J. Irvine, Marco Vitória, Nathan Shaffer ¡ 9 authors
Introduction The 2013 âConsolidated guidelines on the use of antiretroviral (ARV) drugs for treating and preventing HIV infectionâ [1], released in July 2013, are the latest and most comprehensive of a series of important guidelines on antiretroviral therapy (ART) over the last decade from the World Health Organization (WHO). They were developed in response to important advances in the science and practice of HIV care since publication of the 2010 WHO guidance for adults and adolescents [2], pregnant women [3] and children [4]. This includes evolving evidence on the preventive and individual clinical benefits of earlier ART, innovations in service delivery such as the progressive decentralization of HIV testing and care, and the more widespread availability and affordability of once-daily fixed-dose combinations (FDCs) ART regimens [5]. In this special supplement of AIDS, we present a series of thirteen articles and five commentaries covering key aspects of the consolidated guidelines: the process, evidence base, recommendations and guidelines implementation. In this first article, we describe the WHO process and methodology of developing these guidelines. This is followed by seven selected systematic reviews [6â12] that provided the evidence base for specific recommendations. They are presented under the section heading of the relevant guidelines population or topic: Adults and adolescents (when to start ART) [6]; Pregnant women (safety of efavirenz in pregnant and breastfeeding women) [7]; Children (what ART regimen to use in children under 3 years) [8]; ART monitoring (how to monitor treatment response in adults and children) [9,10]; Service delivery (evaluation of effectiveness of service delivery innovations of decentralization and integration) [11]; and different strategies to improve treatment adherence [12]. The systematic reviews in each section are prefaced by commentaries written by the co-chairs and/or members of the Guideline Development Groups (GDGs) that highlight key recommendations and their rationale, and provide additional context for guidance [13â17]. The International HIV/AIDS Alliance and the Global Network of People Living with HIV (GNP+) report on the findings (and lessons learnt) from their consultation on community values and preferences that also informed many of the recommendations [18]. The three concluding articles all address different aspects of the critical phase of country-level adaptation and implementation of the guidelines. This includes what is known about the current status of national adoption of the recommendations in WHO ARV guidelines [19], projections of the global impact and cost of implementation of new recommendations [20] and country-level implications of implementing these guidelines for policy makers, such as diversification of service delivery models, generation and use of data, healthcare financing, human resource capacity and supply chains for drugs and diagnostics [21]. This supplement is not intended to be an exhaustive collation of all the evidence that informed the consolidated guidelines. Several of the commissioned systematic reviews as well as modelling studies have already been published in the peer reviewed literature or are in development [22â28], and a companion AIDS supplement published in January 2014 has already collated other modelling work that contributed to the guidelines process [29]. A comprehensive summary of all supporting evidence is provided as Web Annexes in the guidelines website (http://www.who.int/hiv/pub/guidelines/arv2013/annexes/en/index.html). Distinctive features of the 2013 WHO consolidated guidelines The 2013 consolidated guidelines were distinctive from previous WHO ART guidelines, or other international ART guidelines in several ways. Providing guidance across the entire continuum of HIV care More than fifty new recommendations are provided across the cascade of HIV care, from HIV testing and diagnosis, linkage to care, using ART for prevention, ART initiation, monitoring for treatment failure and ART toxicity, and retention in care. This comprehensive approach responds to the needs of programme managers who are responsible for delivery of care across all of these steps. Expanding guidance: clinical, operational and programmatic In addition to the usual clinical recommendations, there is operational guidance on how to improve delivery of HIV care (with recommendations on task shifting, decentralization, integration and adherence and improving retention in care). The guidelines also provide a framework and tools for programme managers to consider in prioritizing implementation of recommendations according to their national context, including HIV epidemiology, levels of ART uptake, health workforce capacity and available financial resources. This integrated approach better reflects the complex interplay between clinical recommendations and implementation at facility and programme level. Addressing all ages and populations Instead of separate ART guidelines for adults, pregnant women, adolescents and children, as in previous years, guidance is provided across all age groups and populations of adults, pregnant and breastfeeding women, adolescents, and children, as well as those coinfected with tuberculosis (TB), hepatitis B and/or hepatitis C. This enables a more harmonized approach to ART regimen choice, simplifying both the role of healthcare providers, and procurement and supply chain management. Target audience: programme managers in low-income and middle-income countries As for other WHO guidelines, the primary target users are country policy makers and programme managers responsible for national and regional policy and planning decisions on ART scale-up, and in settings with limited resources. Incorporating the key guiding principles of the public health approach and health equity in ART scale-up The 2013 guidelines, as with previous WHO ART guidance, are based on a public health approach to ART scale-up that promotes simplified and standardized approaches to treatment and monitoring that facilitates the widest possible access to high-quality care at the population level [30]. This in turn requires innovations in service delivery to maximize the efficiency of HIV programmes such as through integration of HIV care with other services (e.g. maternal and child health, TB and drug dependence), improved treatment adherence and retention in care, harmonized ART regimens and more affordable diagnostics. Another key guiding principle underpinning implementation of the guidelines is promotion of human rights and health equity in national HIV policies and programmes, so that expanded access is fair and equitable; priority for ART initiation is given to those most in need; and care is provided in a supportive and responsive environment, free of stigma and discrimination. Linking new recommendations with existing guidance New recommendations on the use of ART for treatment and prevention have been harmonized with relevant selected recommendations from existing WHO guidance on HIV testing, prevention and management of coinfections. WHO guidelines development process and the GRADE approach The revision process for the 2013 guidelines was initiated in early 2012, and conducted in accordance with procedures established by the WHO Guidelines Review Committee, to ensure that WHO guidelines are developed using a transparent, evidence-based, decision-making process [31]. Since 2008, WHO has used the internationally agreed standard of the GRADE approach (Grading of Recommendations, Assessment, Development and Evaluation) to assess the quality of a body of evidence, formulate recommendations and rate their strength [32â38] (GRADE working group: http://www.gradeworkingroup.org). Quality of evidence and strength of recommendation GRADE classifies the quality of evidence into one of four levels: high, moderate, low and very low. The rating of quality of evidence from randomized controlled trials starts as high, but may be decreased because of risk of bias, inconsistency in results across studies, indirectness of evidence, imprecision and publication bias [34â36]. The rating of evidence based on observational studies starts as low, but may be increased if the magnitude of the treatment effect is very large, there is evidence of a doseâresponse relationship, or if residual biases would underestimate the effect size [37]. In addition to the quality of the evidence, other considerations in formulating recommendations and rating their strength include the overall balance of benefits and harms to the individual and at a population level, community values and preferences, resource use, cost-effectiveness, feasibility and constraints to implementation in multiple settings, equity and human rights implications [38] (Table 1).Table 1: Key domains considered in formulating recommendations and determining their strength (strong or conditional).GRADE also classifies strength of recommendations as either âstrongâ or âconditionalâ [38]. A strong recommendation is one for which the GDG was confident that the desirable effects of the recommendation outweigh the undesirable effects, while a conditional recommendation is used when it is concluded that the desirable effects probably outweigh the undesirable effects, but there is uncertainty about these trade-offs. The higher the quality of evidence, the more likely a strong recommendation can be made. A conditional recommendation is more likely when high-quality evidence is absent, the estimates of effect are imprecise, there is uncertainty or variability in how individuals value the outcomes, or the benefits are either small or not considered worth the costs. The implications of a conditional recommendation are that, although most people or settings would adopt the recommendation, some would do so only under certain conditions. The following sources of evidence and supporting material were used to inform the development of the new recommendations. Systematic reviews Systematic reviews were commissioned on forty-six topics across the continuum of HIV care, including nine on when to start ART; eleven on what ART to start; four on monitoring the response to ART; six on monitoring toxicity; and eleven on operational aspects of service delivery. The questions were framed using the Population, Intervention, Comparison and Outcome (PICO) format [33], and outsourced to seven different research teams and organizations through a process of competitive tendering. These groups then developed search protocols and conducted reviews of the available scientific evidence. A standardized GRADE evidence table was used to present quantitative summaries of the evidence and assessment of its quality for each PICO question by outcome [32]. The full list of review questions, search protocols, GRADE tables and evidence summaries for each topic are available at http://www.who.int/hiv/pub/guidelines/arv2013/annexes/en/index.html. Seven systematic reviews are included in this supplement [6â12], and others have been published elsewhere [22â28], or are in development. Consultations on community values and preferences An assessment of community values and preferences on key ARV guideline topics was coordinated by the International HIV/AIDS Alliance and the Global Network of People Living with HIV (GNP+) through both an online e-survey (n = 1088), and moderated e-forum discussions with civil society networks (n = 955) [18,39] in six languages (Arabic, Chinese, English, French, Russian and Spanish). Key topics included community preferences regarding possible recommendations (e.g. which ART regimens to use and when to initiate ART for adults, adolescents, pregnant and breastfeeding women, and children), as well as ART service delivery considerations. Four focus group discussions were also held in Uganda and Malawi on the experiences of pregnant women with lifelong ART (option B+). Finally, two e-surveys of health workers caring for HIV-infected adults (n = 98) and children (n = 342) were undertaken on similar topics covered in the community consultation through clinical networks of eight global implementing partner organizations. In addition to the report in this supplement [18], a full consultation document is available [39]. Mathematical modelling of impact and cost effectiveness We commissioned two key modelling projects on health impact (measured using disability-adjusted-life-years (DALYs)) and cost-effectiveness from the HIV Modelling Consortium (http://www.hivmodelling.org) to support the 2013 guidelines. The first examined various HIV testing strategies and criteria for ART initiation in different populations (adults, pregnant women and HIV serodiscordant couples) on the basis of data from countries representative of different HIV epidemic types (generalized, concentrated and mixed) and level of ART coverage [26]. A second project examined different strategies for monitoring treatment response (clinical, CD4+ T-cell count and viral load) and switching to second-line ART [27]. A key strength of these analyses was their use of multiple independently developed models to compare different scenarios, for which there were limited data in the literature. Additional modelling work commissioned included a causal modelling analysis of the impact of starting ART at different ages in children, based on data from the IeDEA South African collaboration [28]. A recent article has highlighted some of the challenges in using modelling data in guidelines development, including the lack of standardized criteria for rating the quality of modelling, and clarity on the positioning of modelling within the GRADE framework for decision-making [40]. It concludes with some key considerations to guide the future use of modelling in guidelines development. Feasibility surveys Reports were commissioned on country implementation experiences, including adoption of lifelong ART in pregnant and breastfeeding women (option B+) in Malawi; introducing tenofovir (TDF) in first-line ART regimens in Zambia; phasing out stavudine (d4T) in Zimbabwe; and scaling up viral load monitoring in MĂŠdecins Sans Frontières programmes in southern Africa. These are summarized in the consolidated guidelines web annexes (http://www.who.int/hiv/pub/guidelines/arv2013/annexes/en/index.html). Impact assessment of implementation of recommendations An impact assessment was undertaken using the AIDS Impact Model (AIM) and Goals model within the Spectrum modelling system [41] to estimate the number of adults and children newly eligible for ART, based on the new treatment recommendations [20]. It also examined the cost and impact that would result if ART coverage expanded to 80% of those eligible for ART. End-user survey to inform guidelines presentation and dissemination strategies An additional preparatory activity was the conduct of an internet-based survey of country-level end-users of recent WHO HIV-related guidelines. This was undertaken to understand better how WHO ART guidelines are used, and identify areas for improvement in format, presentation and dissemination of the new guidelines. The survey targeted WHO National Program Officers and Ministry of Health HIV focal persons, and was administered in English, French, Russian and Spanish between June and September 2012. Overall, there were 78 respondents from 44 countries across all regions (28% South East Asia and Western Pacific, 26% from Central and Eastern Europe, 10% Latin America and Caribbean, 28% Sub-Saharan Africa, 8% Middle East). All respondents had used at least one of twelve WHO HIV guidelines, and the majority (75%) had used them primarily in the development of national guidelines. Although the response rate was limited, and not fully representative of all end-users, there was a good geographic spread of respondents, and several consistent observations emerged. There was a broad agreement that the most critical guideline components were clearly stated recommendations with brief evidence summaries and a clear rationale supporting the recommendation (with inclusion of GRADE tables only as part of web annexes). The value of best practice examples from a wide range of different settings to support implementation was also highlighted. Specific suggestions to enhance readability included reduced length, larger font size, and greater use of colour, summary tables and algorithms. Accessibility and user engagement in dissemination of new WHO HIV guidelines were highlighted as critical factors influencing effective country-level adaptation and implementation. Specific activities to facilitate regional and country-level dissemination of the guidelines activities were in-country workshops and webinars; the availability of guidelines in all UN languages, particularly Arabic, Chinese and Russian; the continued need for printed in addition to electronic versions of the guidelines; and an improved notification system for new guidelines using e-mail together with conference and website announcements. Guideline development groups (GDGs) and process of formulating recommendations The development of recommendations was undertaken by four separate, external technical and and Service and but as a process to ensure an integrated guidelines document for adults, pregnant and breastfeeding women and There were more than GDG members across the four HIV country HIV programme guideline from or other development and of civil society and/or networks of people with HIV on the basis of four technical and regional previous with guidelines We a balance of by and All external members of the and external peer review group WHO of that included in and research support and financial There was also a at the GDG of by members within or clinical trials on either the of ART, or of specific ART Overall, the WHO and of each GDG were that there had been a of and that from the Four GDG were held in between and January The decision-making process and of recommendations first a critical review of the evidence based on systematic reviews of randomized clinical trials observational It also considered of the overall balance of benefits and harms to the individual and at a population level, community values and health preferences, resource use, cost-effectiveness, feasibility and constraints to implementation in multiple settings, and of equity and human The both the of the recommendations and the rating of its strength (strong or All decisions were by and on the recommendations, including their strength if the to be to the recommendations. were through e-mail and recommendations and of of the guidelines were to GDG and a full of the guidelines was to GDG members and peer for A group including of the four was held in 2013 to ensure and of recommendations across the guidelines. Key strength of recommendations and quality of evidence In July 2013, the guidelines were at the International AIDS conference held in and as a printed and electronic including a policy brief in seven languages (Arabic, Chinese, English, French, with an additional web that includes and all supporting and evidence as There were a of new recommendations in the 2013 WHO âConsolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infectionâ were recommendations on adults pregnant and on were on service delivery and four on HIV The most important new clinical recommendations were earlier ART initiation, starting ART in all adults with a CD4+ T-cell count of or prioritizing those with clinical or a CD4+ count than ART initiation of CD4+ count in pregnant and breastfeeding women, children under of HIV-infected in serodiscordant and those coinfected with or hepatitis B a first-line ART regimen of or efavirenz as a once-daily fixed-dose for adults, pregnant women and children 3 and and the use of viral load testing as the approach to monitoring ART response and treatment There were four recommendations on of testing, and also recommendations on improving the efficiency of HIV through ART delivery to primary healthcare and community ART services within child health and other to address in health and strategies to improve retention in care, and adherence to ART. the strength of recommendation and quality of evidence for all recommendations, and then according to population and of the recommendations were as and based on low or very low quality of evidence. The recommendations were of which were based on low and on very low quality evidence. were according to population and All of the service delivery and HIV testing recommendations were as with of the and of the recommendations. all strong service recommendations were based on low or very low quality evidence, this was for the twelve strong recommendations, and only of the strong recommendations in The evidence base in HIV care and for service delivery is well and these were as priority areas for operational and implementation research the guidelines More there are key challenges in consistent adherence to the GRADE guidance on rating of recommendations as strong than There is also a need to address a and some guideline group members that a conditional recommendation may not be and by strong recommendations are based on low quality evidence, it is critical that a clear rationale is A recent of recommendations from different WHO guidelines that had used the GRADE approach also that strong recommendations based on low or very low quality evidence were of strong so this is not specific to HIV care of strength of recommendations and rating of quality of evidence of recommendations in 2013 consolidated dissemination and the of the guidelines, WHO and regional have with national of health and in-country to support national and adaptation through a series of regional dissemination workshops South and held between July and The consolidated guidelines be reviewed and two as new evidence and practice in the use of ART. In there be through technical and programmatic guidance, with one in early 2014 on early diagnosis, scale-up of viral load monitoring and drug and in July 2014 on management of important including HIV-related and hepatitis use of linkage and retention in care, and community ART An science was held with key in and of key research in the 2013 consolidated guidelines and the research to inform development of future WHO also consolidated guidelines in 2014 in two other Key and which provide a of quality for HIV prevention and treatment The the of all members of the Guidelines Development and in the of the four and and for AIDS and of and Network for the of Children by AIDS, and Service for and and of South of and of Health and The WHO of the and and and We also and for with the conduct of the WHO guidelines of There are of
HIV/AIDS Research and Interventions
HIV-related health complications and treatments
Pneumocystis jirovecii pneumonia detection and treatment
Charles B. Holmes, Yogan Pillay, Albert Mwango, Jos PerriÍns ¡ 9 authors
Introduction To successfully implement the 2013 WHO consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection at country level, the implications for national and regional health systems need to be considered and addressed. The guidelines target the entire continuum of care for the HIV-infected individual, and in some cases, their partners, and those with unknown status. The guidelines include not only a more inclusive treatment initiation threshold of CD4+ T-cell count of 500 cells/Îźl or less for adults and adolescents, treatment for life for pregnant and breastfeeding women (or treatment for the duration of pregnancy and breastfeeding regardless of CD4+ T-cell count), treatment regardless of CD4+ T-cell count for children under 5 years of age, discordant couples, those co-infected with either tuberculosis (TB) or severe hepatitis B virus (HBV), and diversification of effective strategies to reach those with unknown status through couples testing and community-based testing. These changes, if fully enacted, will lead to an increase in treatment eligibility of over 60%, from 17.6 million globally, to 28.6 million globally, with variation in that increase by epidemic type and other epidemiologic factors [1]. However, within these increases in volume, health systems will be serving a healthier mix of patients starting antiretroviral therapy (ART), and greater proportions of pregnant women and children, and sexual partners seeking care together. The increased patient volumes and changes in the composition of those seeking care will require rapid attention to existing care delivery strategies in order to ensure that newly diagnosed individuals are served with the maximum efficiency and effectiveness, and others entering or already within the system under existing guidelines are not harmed. Additionally, to be successful over the long term, health systems and HIV programs will need strengthened adherence-support strategies. Systems of care that may already be stressed need to be further augmented through innovations, and in many cases provided with additional resources in order to become more efficient, resilient, robust and effective. The âOperationsâ and âService deliveryâ sections (Chapter 9) of the guidelines address these challenges through recommendations for innovations in the models of service delivery, laboratory diagnostics and treatment delivery in the form of fixed-dose combinations (FDCs) to improve the efficiency, reach and quality of the prevention, care and treatment cascade. There are also potential gains from implementing the guidelines that could accrue to and strengthen health systems and communities, such as a healthier and more productive workforce and fewer new HIV infections, especially in newborns, and HIV-related hospitalizations, and these benefits must also be factored into HIV program and country-level decision-making surrounding adoption and adaptation of the new guidelines [2]. Our objective was to examine the implications of the new guidelines across the continuum of care for each of the elements of national health systems, starting with governance and the role of strategic planning and policy, and including diversification of service delivery models, generation and use of data, healthcare financing, human resource capacity, and supply chains for therapeutic and diagnostic commodities. Governance, strategic planning and policy The progress of discovery and change in the HIV epidemic have demanded a high degree of engagement with evolving evidence, as reflected in part by the 10 guidance documents on antiretroviral drug use issued by WHO since 2000. To date, national governments, with the support of civil society and cooperative partners, have employed a variety of approaches to new guideline adoption. Whereas earlier approaches often focused largely on clinical issues, there is now a need for much broader adoption processes to consider the complex interplay between clinical objectives, operational feasibility, issues related to equity, affordability and health systems capacity. In order to consider, adopt and implement new national guidelines with a broad coalition of support, Ministries of Health must take a strong leadership and governance role. When performed well, the key elements of the process at national level include the following: An inclusive and transparent consultative process that draws upon the best available resources, including program experts and managers, healthcare providers, civil society including people living with HIV, community and faith-based groups, key populations, technical specialists, other relevant government Ministries (e.g. Finance), budget experts and economists, researchers, academics, and health-related professional associations. Assembly, analysis and presentation of relevant clinical, programmatic and financial information. Consideration of guidelines changes in light of broader strategic policy frameworks cross-cutting a broader array of health, human rights and development issues. Clear decision-making mechanisms that allow consideration of competing demands. Clear articulation of roles and responsibility of various partners, in order to ensure accountability and oversight of the processes of change. Ensuring that the case for health in national development, including the potential benefits and risks of potential guidelines changes, is clearly communicated early and often to political leadership and external development partners. The recent process of developing and adopting new guidelines for antiretroviral drug use in pregnant and breastfeeding women in Zambia provides an instructive example of the range of activities needed to ensure that guidelines changes are made with broad stakeholder and health systems support (Fig. 1) [3,4]. National governments and civil society are encouraged to learn lessons from peers, and to participate in WHO's regional guidelines dissemination workshops that are designed to support strong national processes of guidelines change.Fig. 1: The process of changing prevention of mother-to-child transmission (PMTCT) guidelines in Zambia.Diversification and integration of service delivery models to manage patient volumes and improve retention and quality The expansion of HIV testing, care and eligibility for ART will require national governments and partners to consider how best to augment or modify their current health systems to accommodate increased volumes and new categories of patients, and to ensure retention across the care and treatment cascade. There is currently an over-reliance on a limited number service delivery models in many countries. Maximum expansion capacity and quality can be achieved by ensuring that a carefully selected variety of models are put in place and adapted strategically to take account of geography, epidemiology and local needs. Thus, it is an opportune time for governments and funders to focus on previously piloted models that are appropriate for scale-up, and to ensure that the most effective models are scaled up systematically in order to provide substantial complementary capacity to absorb new patients and provide ongoing care. Within the new guidelines, there is an increased emphasis on the importance of expanded national HIV testing and counseling strategies in order to identify âas many people living with HIV as early as possible after acquiring HIV infection, and link them appropriately and in a timely manner to prevention, care and treatment servicesâ. The reality of most HIV-testing programs in most generalized epidemics is that they have been largely dominated by provider-initiated testing (most typically healthcare provider-initiated), which has been favored because of the ease of linkage to services and for its high yield and cost-effectiveness. However, it often identifies people living with HIV late in the course of HIV disease, in particular, men and adolescents, as well as key populations, who have low utilization of healthcare services. With the guidelinesâ strong recommendation for community-based HIV testing and counseling with linkage to prevention, care and treatment services, governments should consider systematically expanding a number of approaches tailored for their settings, including mobile, door-to-door, index, campaign, workplace and school-based HIV testing and counseling approaches, and other strategies that ensure the inclusion of underserved groups such as children, adolescents and men. It is also important to recognize that the yield of nonclinic-based testing can be lower and more expensive from a human resource perspective, requiring a careful balance to be struck. For concentrated and low-level epidemics, governments are urged to consider guidelines that reflect WHO's strong recommendation to increase the number and diversity of the facilities in which provider-initiated testing and counseling are available, including sexually transmitted infection clinics, hepatitis and TB sites, antenatal care settings and services for key populations, notably MSM, transgender people, sex workers and people who inject drugs (Fig. 2) [5].Fig. 2: Innovative service delivery models to increase diagnosis and early antiretroviral therapy (ART) initiation among key populations in Indonesia.The capacity of national health systems to absorb the greater numbers of healthier, pregnant and individuals accompanied by partners eligible for treatment will be directly related to the extent to which ART sites are diversified, decentralized (and in some cases integrated into primary care services) and generally expanded. Extending care through different models will also relieve traditional ART sites and higher-level facilities and allow a greater focus on the sickest patients, especially in high-burden generalized epidemics. Models for consideration and rapid scale-up include ART initiation and maintenance for mothers and children in high HIV-prevalence settings integrated into antenatal care, and maternal and child health clinics, and for HIV/TB co-infected individuals into TB clinics, and other approaches that reduce the need of patients to come to clinics through community-based treatment clubs with rotating antiretroviral drug pick-up and home delivery, especially in remote rural areas. A systematic review on the impact of decentralization of ART delivery identified evidence from both randomized controlled trials and observational studies, and found that patients initiated at a hospital and maintained at a health center were more likely to be retained [6]. No difference in attrition was observed between those initiated and maintained on ART at a hospital compared to at a health center. Comparable attrition was observed after 12 months in the two trials in which ART maintenance was in the community [6]. Regions with measurable injection drug use may also consider the new strong recommendation for ART initiation integrated into clinics and sites in which opioid substitution therapy (OST) is provided. In areas with strong general outpatient services, integration of HIV services may yield greater equity with other health services, and may more directly enable HIV's chronic care models to benefit care and management responses to other chronic diseases such as diabetes and hypertension. These integrated sites must also be capacitated with on-site laboratories and referrals with a rapid turnaround for results reporting, especially for viral load, CD4+ T-cell count testing, TB testing and safety laboratories. Tiered laboratory systems must work closely with program leadership to ensure strategic investments in the best technologies for sites providing ART. Intentional analyses should be conducted to balance the convenience of point-of-care (e.g. CD4+ T-cell testing) technologies with the use of centralized high-throughput instruments. With anticipated rapid expansion of demand for viral load testing, it is essential to use internationally acceptable methods to locally validate the use of dry blood spots, as a means of viral load testing, which will allow expansion of this capacity without phlebotomy and cold chain capacity â the imminent availability of point-of-care viral load testing will also strengthen the health system's ability to provide good quality care. It is also critical to close the loop with results reporting via short message service or other secure electronic communication. Existing and new models also need to be chosen in order to intentionally retain patients in care and treatment, and ensure adherence to ART. Structural interventions such as increasing access points and decentralization through community-based models can address some of the most commonly cited reasons for disengagement with care (e.g. transport expenses, overcrowding of vertical sites). At an individual level, substantial evidence has demonstrated the benefits of two-way mobile phone text message systems, and WHO has made a strong recommendation for consideration of this approach [7]. As with numerous other proven methodologies, very few countries have systematically evaluated the needs of various vulnerable groups such as pregnant women, adolescents, key populations and healthy individuals starting ART and systematically taken appropriate packages of cost-effective adherence and retention interventions from the pilot phase, to scale. Generation and use of data for monitoring, evaluation, efficiency and quality improvement National and regional health systems of program monitoring and evaluation are fundamental to public health approaches to HIV prevention, care and treatment, and other chronic illnesses. When they work well, systems of measurement serve to provide actionable data for decision-making, starting with the clinician and service delivery sites, to regional and national program managers, related sectors (e.g. Ministries of Finance), and development partners [8]. Although the HIV response has focused substantial investments on monitoring and evaluation, the nature of the emergency response combined with weak health systems and the sheer volume of chronically ill patients have resulted in greater than expected challenges for many national systems. These challenges have been highlighted in recent studies demonstrating serious gaps in the ability of these systems to report on indicators that meaningfully measure program quality, and a lack of consistent data use at the site and regional levels to improve program quality [9]. With the influx of individuals seeking testing and care, and through sites and models not traditionally reporting on ART use (e.g. community-based antiretroviral drug pick-up and antenatal care sites), there are actions that must be taken coincident with guidelines adoption to ensure effective monitoring and evaluation of program quality. National governments and supportive cooperative partners must redouble efforts to harmonize and strengthen platforms for the use of data at levels of the health system to ensure that guidelines changes are as expected and that quality of care and patient are not models include or by the of health and development partners their implementing to review care and treatment at the and local These processes should be to and quality improvement processes that ensure clinical sites review their on critical elements of the care and treatment and have to to to quality and access to technical as on data use also to attention on the volume and of indicators and the systems that data A of potential indicators over the years has in some cases attention from those indicators considered at regional and national and countries are encouraged to their most critical indicators with the and ensure in the WHO's early indicators for HIV drug system of key indicators designed to quality improvement of ART services at level, with for and of the results for program management National governments and development partners also need to ensure systems are to allow reporting and use of the There are numerous and systems in few are fully integrated across the of care and treatment and at a national WHO is with numerous countries to improve integration of systems the Systems for HIV a of and guidelines to countries and implement a system that patient and and the impact in an integrated across maternal and child health of mother-to-child transmission and In WHO will consolidated strategic guidance that will a of indicators across the continuum of prevention, treatment and these will the key of quality HIV With this HIV program will have access to the critical indicators within with other When data are not to and important areas of the other methods may be including use of to more on critical issues that can with program quality, and traditional indicators and studies to the of critical program changes (e.g. studies of pregnant women starting ART CD4+ T-cell count of models and efficiency The HIV response ongoing and attention to to ensure the availability of for effective and with the Although the new guidelines will have much greater impact on health and of new and have the potential to reduce the of their are [1]. Ministries of Health and have critical challenges with new guideline to the and financial of potential guidelines changes in order to with local planning and to secure to support ongoing and changes to and to ensure the use of available of the of potential guidelines changes can be a variety of models, and some countries have been these of for As in of the guidelines, the of models is of the most commonly and its and resource needs models can be to the impact of guidelines changes on number of number of infections, and the of changing guidelines or approaches in a variety of epidemic models include the Health and models by the Health and for each with various and potential are encouraged to consider that is only as good as its ease of level of support, and attention must be in to ensuring the of local programmatic and Although has the of for the HIV response over the 10 years of the response in many low and some national governments have to increase their The ability of the in low and countries to further support the HIV and broader health response will be especially if traditional to These new guidelines a case for changing the course of the HIV and further resource may be by the of (e.g. more in antiretroviral drugs in the may reduce HIV that are less at for These may also be in the of such as the for Health and as for development of national that have the potential to provide a more for the HIV response and general health The has a to with to increase for methods for the efficiency by which the healthcare system resources to key and will also to and further resource For to the range of to provide ART to an individual, or provide an HIV testing and counseling by or of and for activities partners have made investments in developing these methods over recent and national governments are encouraged to to and resource use as the new guidelines are Ensuring human resource capacity to support evolving service delivery models of to the range of services to quality healthcare are a chronic in many countries. in many low and with of patients, are in some cases by only clinical and to long and for patients and a lack of attention to quality the new guidelines have many of the HIV interventions (e.g. a available in for HIV-infected and a focus on ensuring patients ART they HIV-related illnesses. These will further allow national programs to care delivery to who require less and to service delivery models and community delivery of The new guidelines also include recommendations for ART initiation to and for and community health workers to ART between has been a in the evidence for these recommendations and has successfully as a means of increasing the number of sites and to serve HIV-infected individuals (Fig. The effective use of in as a means of and expanding access to HIV care and as countries and scale-up new models of delivery, the guidelines changes provide a good to the current of various levels of and to use rapid evaluation to For the has that allow national governments to the need for additional healthcare workers on various guidelines These can also countries to approaches to and healthcare including laboratory These can form the for with professional of laboratory and and programs for other including community health workers and In order to the potential of the health including substantial numbers of new of health governments must to monitoring of program and ongoing support for the development of healthcare It is also important to frameworks to enable support and for new of health workers that have proven essential to the HIV including and community health These with the to have often been considered now are upon for delivery of services and must or and for Ensuring national supply chains are for the increase in volumes and changes in the mix of of the critical interventions in the new guidelines are on a consistent supply of essential commodities. Although national supply chains have in the 10 years of the HIV especially for antiretroviral drug there serious challenges in ensuring that clinics have For of rapid at the site level the efficiency and of and testing and prevention programs With more and expanded testing capacity for individuals their CD4+ T-cell count 500 cells/Îźl the case of and rapid expansion of viral load capacity, countries will to ensure that and related are with the of as antiretroviral activities for the of new guidelines include of the capacity of the and human resource capacity for transport and data management of the national supply for and need to include on antiretroviral drug that the use of fixed-dose in order to ensure adherence and supply the potential for viral load testing to up demand for and for additional HIV rapid (and other of care diagnostic such as point-of-care CD4+ T-cell and TB testing and and antiretroviral drug of of the of supply and of available technical and national of of with accountability at the levels of government and will likely have the with ensuring of key such as HIV rapid antiretroviral drugs and critical laboratory if their demand are communicated to their or supply and into The is important because the them and the to TB and work with to the demand for various of which the to the demand for their In the this and financial to of by of health services as well as civil society should be encouraged by national governments to ensure that are as early as possible that may be In the new WHO consolidated guidelines reflect not only evolving clinical also in the and of service delivery and program The most effective processes of guidelines change are by and reflect consultative processes in which and can be by partners with a in the It is expected that most countries will that there is a need to investments in the diversification of service delivery models, use and of data, development of human resources, and supply chains in order to accommodate increased patient volumes and to quality across the care and treatment cascade. and with careful for the essential elements of national health systems, the new guidelines could yield substantial for individuals living with HIV and public of There are of
In 2010, the fourth decade of the HIV pandemic arrived during a time of unprecedented success in HIV prevention. Globally, UNAIDS estimated that new HIV infections fell by 33% between 2001 and 2011; new infections among adults and adolescents fell by 50% or more in 26 countries (more than half of these countries were in sub-Saharan Africa), and new infections among children worldwide dropped by 52% [1,2]. The declines in new HIV infections are particularly evident in countries with sustained and more strategic investments, which take into account the specifics of local epidemics, increased political leadership and community engagement in response to the HIV epidemic, and scale up of HIV prevention and treatment programmes [2]. The rapidly growing delivery of antiretrovirals to women and infant feedingâbased prevention programmes has resulted in a sharp decline in new HIV diagnoses among children. The encouraging declines in HIV infections can also be attributed to the improved effectiveness of combination antiretroviral treatment (cART), an expanded range of improved medications, the declining prices that make cART more accessible to people in low-income countries, growing coverage with HIV testing, and improved access to prevention and treatment services (particularly for women and young people in low-income countries). Global investment in the AIDS response jumped from US$3.8 billion in 2002 to US$18.9 billion in 2012. The new decade also saw a revolution in HIV prevention with ground-breaking scientific advances in HIV biomedical prevention, and specifically, proof that microbicides containing an antiretroviral agent can reduce sexual transmission of HIV to women by 39% [3], that earlier start of treatment by HIV-positive people (treatment as prevention or TasP) can reduce the risk of onward transmission by as much as 96% [4], and that consistent, correct use of a daily antiretroviral tablet by men who have sex with men (MSM) can achieve substantial reductions in HIV infections (pre-exposure prophylaxis or PrEP) [5]. In response to the excitement and optimism surrounding the preventative effects of antiretroviral medications, the UN member states considered and unanimously approved the new Political Declaration on HIV/AIDS at a special session of the General Assembly in New York in 2011 [6]. At the core of the 2011 UN Political Declaration are ambitious new HIV prevention targets calling on governments to commit to reducing sexual transmission of HIV by 50%, reducing HIV transmission though injecting drug use by 50% and eliminating mother-to-child transmission of HIV by 2015. These targets are aimed at reinvigorating the commitment towards achieving the Millennium Development Goal #6 to combat HIV/AIDS [7]. In the past two years, research on HIV biomedical prevention has focused on adapting the new prevention strategies to the context of local HIV epidemics [8]. There have been equal measures of optimism and pessimism expressed about the ability of new prevention strategies to halt the HIV pandemic. Based on the evidence that starting treatment earlier can increase health benefits and extend life for people with HIV [9,10], many clinicians are already recommending early treatment for both medical and TasP purposes. Regarding PrEP, the widespread reaction is caution in recommending this strategy. Such reluctance is based on concerns about the common adherence issues in the studies of PrEP [11], the obvious relationship between level of adherence to daily medication schedule and its preventative effect [12] and side effects and drug-resistant HIV [13], among others. Despite little evidence that PrEP use can affect behaviour, many concerns have been voiced about the future of safe sex practices, particularly condom use among MSM, if new biomedical prevention strategies are introduced. More research is needed to investigate this issue using appropriate study designs. In its current form, daily PrEP may benefit only a small number of people with very high and ongoing risk for HIV infection, and other PrEP regimens must be explored. The overarching concern about new prevention strategies, particularly PrEP, is that the cost and burden of providing them are currently unacceptable for most, even high-income, countries. As a result, there have been calls for more evidence and a very slow progress in implementing these two new exciting HIV prevention developments. Regarding PrEP, only two countries to date have prescription guidelines for people at high risk of HIV infection [14,15]. We now have the knowledge and new tools to revolutionize HIV prevention, and we have the bold new Political Declaration with ambitious targets. It must be acknowledged that the task of bringing HIV infections down to zero seems daunting from where we stand now in late 2013. Despite the global success in lowering the HIV infection rates by 33% [1], sub-Saharan Africa has seen only a 25% decline [16]. Some regions have seen increases (8% in Eastern Europe and central Asia [17], 19% in East Asia [18] and 37% in the Middle East and North Africa [19]). This lack of progress has been associated with insufficient resources, inadequate coverage of women with antiretroviral treatment and HIV testing programmes not reaching the population groups at high risk for HIV infection. While sexual behaviour has changed to become safer in some countries and populations, sexual risk taking has increased in other settings. This is the case in most high-income countries in North America, western and central Europe and Australasia, where MSM are central to local HIV epidemics. In these countries, both high-risk sexual practices among MSM and HIV infections have been on the rise [20,21]. Condom use has increased in some countries, but declined in others. Proven effective interventions (e.g., prevention of mother-to-child transmission (PMTCT) and needle- and syringe-exchange programmes) have not achieved sufficiently high coverage in many countries [1]. Although trends in risky sexual practices have been linked to the trends in HIV incidence [22] and population-level behaviour change to the reduction in HIV prevalence, there are still challenges in linking behaviour-change programmes to specific HIV outcomes on the population level [2]. While new expectations have been raised about the role of antiretrovirals for HIV prevention, mixed progress was observed in access to cART, and only 61% of people eligible for treatment under the 2010 WHO guidelines received it (this is as little as 34% under the 2013 WHO guidelines). The Political Declaration has for the first time named and acknowledged the importance of such population groups as MSM, people who inject drugs and sex workers for HIV prevention, but in many settings, stigma and access to treatment and prevention services for these groups are still important challenges. Many low- and middle-income countries have stepped up their local investments in HIV prevention [2], but, regrettably, the lack of resources has remained a major issue: only US$18.9 billion was available from all sources for the AIDS response in 2012, and this was estimated to be 16â26% short of annual need [1]. It is at this time of some successes in HIV prevention and challenges in how to optimize the available resources and tools that the aspirational Political Declaration of commitment to fight the pandemic is necessary. This year's International AIDS Day marks the midpoint towards the deadline set by the Political Declaration in 2011. It is an opportunity for governments and each of us to revisit and reinvigorate the universal commitment to bring HIV infections to zero. Like never before, we have good cause to expect the next generation to be AIDS-free and new HIV infections to move towards zero. In the face of the 75 million people who have suffered from HIV/AIDS and the many more affected, the international community should keep the promise and bring this HIV pandemic to an end. None were declared. The Kirby Institute receives project funding from the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. IZ has prepared the manuscript and approved its final version.
Sander Greenland and Charles Poole1 accept that P values are here to stay but recognize that some of their most common interpretations have problems. The casual view of the P value as posterior probability of the truth of the null hypothesis is false and not even close to valid under any reasonable model, yet this misunderstanding persists even in high-stakes settings (as discussed, for example, by Greenland in 2011).2 The formal view of the P value as a probability conditional on the null is mathematically correct but typically irrelevant to research goals (hence, the popularity of alternativeâif wrongâinterpretations). A Bayesian interpretation based on a spike-and-slab model makes little sense in applied contexts in epidemiology, political science, and other fields in which true effects are typically nonzero and bounded (thus violating both the âspikeâ and the âslabâ parts of the model). I find Greenland and Pooleâs1 perspective to be valuable: it is important to go beyond criticism and to understand what information is actually contained in a P value. These authors discuss some connections between P values and Bayesian posterior probabilities. I am not so optimistic about the practical value of these connections. Conditional on the continuing omnipresence of P values in applications, however, these are important results that should be generally understood. Greenland and Poole1 make two points. First, they describe how P values approximate posterior probabilities under prior distributions that contain little information relative to the data: This misuse [of P values] may be lessened by recognizing correct Bayesian interpretations. For example, under weak priors, 95% confidence intervals approximate 95% posterior probability intervals, one-sided P values approximate directional posterior probabilities, and point estimates approximate posterior medians. I used to think this way, too (see many examples in our books), but in recent years have moved to the position that I do not trust such direct posterior probabilities. Unfortunately, I think we cannot avoid informative priors if we wish to make reasonable unconditional probability statements. To put it another way, I agree with the mathematical truth of the quotation above, but I think it can mislead in practice because of serious problems with apparently noninformative or weak priors. Second, the main proposal made by Greenland and Poole is to interpret P values as bounds on posterior probabilities: [U]nder certain conditions, a one-sided P value for a prior median provides an approximate lower bound on the posterior probability that the point estimate is on the wrong side of that median. This is fine, but when sample sizes are moderate or small (as is common in epidemiology and social science), posterior probabilities will depend strongly on the prior distribution. Although I do not see much direct value in a lower bound, I am intrigued by Greenland and Pooleâs1 point that âif one uses an informative prior to derive the posterior probability of the point estimate being in the wrong direction, P0/2 provides a reference point indicating how much the prior information influenced that posterior probability.â This connection could be useful to researchers working in an environment in which P values are central to communication of statistical results. In presenting my view of the limitations of Greenland and Pooleâs1 points, I am leaning heavily on their own work, in particular on their emphasis that, in real problems, prior information is always available and is often strong enough to have an appreciable impact on inferences. Before explaining my position, I will briefly summarize how I view classical P values and my experiences. For more background, I recommend the discussion by Krantz3 of null hypothesis testing in psychology research. WHAT IS A P VALUE IN PRACTICE? The P value is a measure of discrepancy of the fit of a model or ânull hypothesisâ H to data y. Mathematically, it is defined as Pr(T(yrep)>T(y)|H), where yrep represents a hypothetical replication under the null hypothesis and T is a test statistic (ie, a summary of the data, perhaps tailored to be sensitive to departures of interest from the model). In a model with free parameters (a âcomposite null hypothesisâ), the P value can depend on these parameters, and there are various ways to get around this, by plugging in point estimates, averaging over a posterior distribution, or adjusting for the estimation process. I do not go into these complexities further, bringing them up here only to make the point that the construction of P values is not always a simple or direct process. (Even something as simple as the classical chi-square test has complexities to be discovered; see the article by Perkins et al4). In theory, the P value is a continuous measure of evidence, but in practice it is typically trichotomized approximately into strong evidence, weak evidence, and no evidence (these can also be labeled highly significant, marginally significant, and not statistically significant at conventional levels), with cutoffs roughly at P = 0.01 and 0.10. One big practical problem with P values is that they cannot easily be compared. The difference between a highly significant P value and a clearly nonsignificant P value is itself not necessarily statistically significant. (Here, I am using âsignificantâ to refer to the 5% level that is standard in statistical practice in much of biostatistics, epidemiology, social science, and many other areas of application.) Consider a simple example of two independent experiments with estimates (standard error) of 25 (10) and 10 (10). The first experiment is highly statistically significant (two and a half standard errors away from zero, corresponding to a normal-theory P value of about 0.01) while the second is not significant at all. Most disturbingly here, the difference is 15 (14), which is not close to significant. The naive (and common) approach of summarizing an experiment by a P value and then contrasting results based on significance levels, fails here, in implicitly giving the imprimatur of statistical significance on a comparison that could easily be explained by chance alone. As discussed by Gelman and Stern,5 this is not simply the well-known problem of arbitrary thresholds, the idea that a sharp cutoff at a 5% level, for example, misleadingly separates the P = 0.051 cases from P = 0.049. This is a more serious problem: even an apparently huge difference between clearly significant and clearly nonsignificant is not itself statistically significant. In short, the P value is itself a statistic and can be a noisy measure of evidence. This is a problem not just with P values but with any mathematically equivalent procedure, such as summarizing results by whether the 95% confidence interval includes zero. GOOD, MEDIOCRE, AND BAD P VALUES For all their problems, P values sometimes âworkâ to convey an important aspect of the relation of data to model. Other times, a P value sends a reasonable message but does not add anything beyond a simple confidence interval. In yet other situations, a P value can actively mislead. Before going on, I will give examples of each of these three scenarios. A P Value that Worked Several years ago, I was contacted by a person who suspected fraud in a local election.6 Partial counts had been released throughout the voting process and he thought the proportions for the various candidates looked suspiciously stable, as if they had been rigged to aim for a particular result. Excited to possibly be at the center of an explosive news story, I took a look at the data right away. After some preliminary graphsâwhich indeed showed stability of the vote proportions as they evolved during election dayâI set up a hypothesis test comparing the variation in the data to what would be expected from independent binomial sampling. When applied to the entire data set (27 candidates running for six offices), the result was not statistically significant: there was no less (and, in fact, no more) variance than would be expected by chance alone. In addition, an analysis of the 27 separate chi-square statistics revealed no particular patterns. I was left to conclude that the election results were consistent with random voting (even though, in reality, voting was certainly not randomâfor example, married couples are likely to vote at the same time, and the sorts of people who vote in the middle of the day will differ from those who cast their ballots in the early morning or evening). I regretfully told my correspondent that he had no case. In this example, we cannot interpret a nonsignificant result as a claim that the null hypothesis was true or even as a claimed probability of its truth. Rather, nonsignificance revealed the data to be compatible with the null hypothesis; thus, my correspondent could not argue that the data indicated fraud. A P Value that Was Reasonable but Unnecessary It is common for a research project to culminate in the estimation of one or two parameters, with publication turning on a P value being less than a conventional level of significance. For example, in our study of the effects of redistricting in state legislatures (Gelman and King),7 the key parameters were interactions in regression models for partisan bias and electoral responsiveness. Although we did not actually report P values, we could have: what made our article complete was that our findings of interest were more than two standard errors from zero, thus reaching the P < 0.05 level. Had our significance level been much greater (eg, estimates that were four or more standard errors from zero), we would doubtless have broken up our analysis (eg, studying Democrats and Republicans separately) to broaden the set of claims that we could confidently assert. Conversely, had our regressions not reached statistical significance at the conventional level, we would have performed some sort of pooling or constraining of our model to arrive at some weaker assertion that reached the 5% level. (Just to be clear: we are not saying that we would have performed data dredging, fishing for significance; rather, we accept that sample size dictates how much we can learn with confidence; when data are weaker, it can be possible to find reliable patterns by averaging.) In any case, my point is that in this example it would have been just fine to summarize our results in this example via P values even though we did not happen to use that formulation. A Misleading P Value Finally, in many scenarios P values can distract or even mislead, either a nonsignificant result wrongly interpreted as a confidence statement in support of the null hypothesis or a significant P value that is taken as proof of an effect. A notorious example of the latter is the recent article by Bem,8 which reported statistically significant results from several experiments on extrasensory perception (ESP). At brief glance, it seems impressive to see multiple independent findings that are statistically significant (and combining the P values using classical rules would yield an even stronger result), but with enough effort it is possible to find statistical significance anywhere (see the report by Simmons et al9). The focus on P values seems to have both weakened that study (by encouraging the researcher to present only some of his data so as to draw attention away from nonsignificant results) and to have led reviewers to inappropriately view a low P value (indicating a misfit of the null hypothesis to data) as strong evidence in favor of a specific alternative hypothesis (ESP) rather than other, perhaps more scientifically plausible, alternatives such as measurement error and selection bias. PRIORS, POSTERIORS, AND P VALUES Now that I have established my credentials as a pragmatist who finds P values useful in some settings but not others, I want to discuss Greenland and Pooleâs proposal to either interpret one-sided P values as probability statements under uniform priors (an idea they trace back to Gossett)10 or else to use one-sided P values as bounds on posterior probabilities (a result they trace back to Casella and Berger).11 The general problem I have with noninformatively derived Bayesian probabilities is that they tend to be too strong. At first, this may sound paradoxical, that a noninformative or weakly informative prior yields posteriors that are too forcefulâand let me deepen the paradox by stating that a stronger, more informative prior will tend to yield weaker, more plausible posterior statements. How can it be that adding prior information weakens the posterior? It has to do with the sort of probability statements we are often interested in making. Here is an example from Gelman and Weakliem.12 A sociologist examining a publicly available survey discovered a pattern relating attractiveness of parents to the sexes of their children. He found that 56% of the children of the most attractive parents were girls, when compared with 48% of the children of the other parents, and the difference was statistically significant at P < 0.02. The assessments of attractiveness had been performed many years before these people had children, so the researcher felt he had support for a claim of an underlying biological connection between attractiveness and sex ratio. The original analysis by Kanazawa13 had multiple-comparisons issues, and after performing a regression analysis rather than selecting the most significant comparison, we get a P value closer to 0.2 rather than the stated 0.02. For the purposes of our present discussion, though, in which we are evaluating the connection between P values and posterior probabilities, it will not matter much which number we use. We shall go with P = 0.2 because it seems like a more reasonable analysis given the data. Let θ be the true (population) difference in sex ratios of attractive and less attractive parents. Then the data under discussion (with a two-sided P value of 0.2), combined with a uniform prior on θ, yield a 90% posterior probability that θ is positive. Do I believe this? No. Do I even consider this a reasonable data summary? No again. We can derive these âNoâ responses in three different ways: first, by looking directly at the evidence; second, by considering the prior; and third, by considering the implications for statistical practice if this sort of probability statement were computed routinely. First, a claimed 90% probability that θ > 0 seems too strong. Given that the P value (adjusted for multiple comparisons) was only 0.2âthat is, a result that strong would occur a full 20% of the time just by chance alone, even with no true differenceâit seems absurd to assign a 90% belief to the conclusion. I am not prepared to offer 9-to-1 odds on the basis of a pattern someone happened to see that could plausibly have occurred by chance alone, nor for that matter would I offer 99-to-1 odds based on the original claim of the 2% significance level. Second, the prior uniform distribution on θ seems much too weak. There is a large literature on sex ratios, with factors such as ethnicity, maternal age, and season of birth corresponding to difference in probability of girl birth of <0.5 percentage points. It is a priori implausible that sex-ratio differences corresponding to attractiveness are larger than for these other factors. Assigning an informative prior centered on zero shrinks the posterior toward zero, and the resulting posterior probability that θ > 0 moves to a more plausible value in the range of 60%, corresponding to the idea that the result is suggestive but not close to convincing. Third, consider what would happen if we routinely interpreted one-sided P values as posterior probabilities. In that case, an experimental result that is 1 standard error from zeroâthat is, exactly what one might expect from chance aloneâwould imply an 83% posterior probability that the true effect in the population has the same direction as the observed pattern in the data at hand. It does not make sense to me to claim 83% certaintyâ5-to-1 oddsâbased on data that not only could occur by chance alone but in fact represent an expected level of discrepancy. This system-level analysis accords with my criticism of the flat prior: as Greenland and Poole1 note in their article, the effects being studied in epidemiology are typically range from â1 to 1 on the logit scale; hence, analyses assuming broader priors will systematically overstate the probabilities of very large effects and will overstate the probability that an estimate from a small sample will agree in sign with the corresponding population quantity. Rather than relying on noninformative priors, I prefer the suggestion of Greenland and Poole1 to bound posterior probabilities using real prior information. I would prefer to perform my Bayesian inferences directly without using P values as in intermediate step, but given the ubiquity of P values in much applied work, I can see that it can be helpful for researchers to understand their connection to posterior probabilities under informative priors. SUMMARY Like many Bayesians, I have often represented classical confidence intervals as posterior probability intervals and interpreted one-sided P values as the posterior probability of a positive effect. These are valid conditional on the assumed noninformative prior but typically do not make sense as unconditional probability statements. As Sander Greenland has discussed in much of his work over the years, epidemiologists and applied scientists in general have knowledge of the sizes of plausible effects and biases. I believe that a direct interpretation of P values as posterior probabilities can be a useful startâif we recognize that such summaries systematically overestimate the strength of claims from any particular dataset. In this way, I am in agreement with Greenland and Pooleâs interpretation of the one-sided P value as a lower bound of a posterior probability, although I am less convinced of the practical utility of this bound, given that the closeness of the bound depends on a combination of sample size and prior distribution. The default conclusion from a noninformative prior analysis will almost invariably put too much probability on extreme values. A vague prior distribution assigns much of its probability on values that are never going to be plausible, and this disturbs the posterior probabilities more than we tend to expectâsomething that we probably do not think about enough in our routine applications of standard statistical methods. Greenland and Poole1 perform a valuable service by opening up these calculations and placing them in an applied context.
Whether 15 million on antiretroviral therapy (ART) by 2015 is a realistic target or just a dream is posing the question in the wrong way. The real question is: how can we turn our dream of having 15 million HIV-infected people receiving adequate antiretroviral therapy in 2015 into reality? This issue of Current Opinion in HIV and AIDS, although far from comprehensive, provides building blocks to attain that goal, points out particular opportunities, but also identifies some of the obstacles that need to be overcome. The first article by Duncombe et al. (pp. 4â11) sets the stage by summarizing the WHO/UNAIDS Treatment 2.0 strategy. No need to duplicate or add to that here, because the article provides a thorough update on where we stand. One element needs to be highlighted, however: contributions of international donors have been stagnating over the past years, and although there is a continued increase in domestic funding, most African countries are far from reaching the Abuja Declaration targets for spending on healthcare. Sure, efficiencies in healthcare delivery can be improved [1], and the striking levels of fungibility or crowding out [2] may be tackled by innovative ways of donor financing [3]. But if there is too little money overall to provide decent healthcare, targets cannot be met. The second article by Vittoria and Vella (pp. 12â18) provides a very nice overview of the evolution of WHO HIV treatment guidelines, adapting to changing insights and possibilities throughout the years in an ever more timely manner. It also points at future trends, which take into account the beneficial effects early treatment can have on the health of individuals, HIV transmission, the incidence of tuberculosis and models of care delivery. If we do not succeed in simplifying models of care delivery, by decentralization and task-shifting a.o., we will be unable to reach the 15 million by 2015 target. The third article, by Hamers et al. (pp. 19â26) and the fourth article, by Sohn et al. (pp. 27â33) focus on transmitted HIV drug resistance in Africa and Asia, respectively, and point to an emerging and in some countries, like Uganda, already sizable problem. The Hamers article also presents data on the high rate of drug resistance mutations in those failing first-line therapy. It is clear that surveillance of both transmitted and secondary HIV drug resistance and measures to minimize the risk of their emergence (such as preventing drug stock-outs and increasing adherence) should be an integral component of the continuing ART scale-up. The 15 million target stands for 15 million people on effective, not failing, highly active antiretroviral therapy. Hill (pp. 34â40), in the fifth article, identifies three main problems with the current ART standard of care for many people in resource-poor settings: a large proportion of those on treatment are still taking stavudine-containing ART; there is limited diagnostic support â access to plasma viral load and drug resistance testing is still rare, which leads to late diagnosis of therapy failure and accumulation of drug resistance mutations; access to second-line treatment is limited. Thus, current practice often does not meet the standards deemed necessary by Hill to achieve âUniversal Accessâ: a simple system of treatment, using a sequence of low-cost, coformulated antiretrovirals with strong efficacy profiles, nonoverlapping resistance profiles, and safety issues which are manageable with minimal medical expertise. He argues that only a relatively small subset of antiretrovirals may be needed for first-line, second-line and potentially third-line treatment in large-scale treatment access programs, and has several creative ideas about how this could be achieved in the most cost-effective manner, with a focus on ongoing research to use lower dosages of drugs (âdose-optimizationâ) which are cheap to manufacture. One can argue whether stavudine should have been included in this list, but, overall, simplifying therapeutic algorithms and lowering the dose and thus the cost of individual drugs are essential ingredients of a more effective scale-up. The sixth article (pp. 41â49), by the âfathersâ of Treatment as Prevention (TasP), advocates passionately for expansion of combination HIV prevention with an emphasis on the merits of expanding treatment: there is increasing evidence of health benefits of earlier treatment, a sharp reduction in incidence of tuberculosis in HIV-infected individuals, and with viral suppression through effective ART the risk of passing on the virus from a person living with HIV to a negative partners is close to zero. The authors remind us about the early skepticism regarding the feasibility and advisability of delivering ART in resource-poor settings, and how these skeptics have been proven wrong. Yes, we should never ever be discouraged by âthe nattering nabobs of negativismâ (to use a phrase from the recently deceased William Safire). But we can also not be naĂŻve and ignore the potential risks. The path to âTest and Treatâ will be paved by identifying â and managing â the potential risks; long-term side effects, and development of significant drug resistance, for example, because of breeches in adherence in particular of people living with HIV who have never been sick and as such have not felt themselves the dramatic benefits of treatment and full reconstitution of ill-health. The question should be less whether or not to treat earlier. But much rather about the âhowâ and what needs to be in place to minimize, track and manage the potential risks. Let us move intelligently, and while proceeding, watch carefully for possible negative effects to take corrective action, and take the emerging results and lessons of ongoing TasP demonstration projects into account. The seventh article, by Hankins and Dybul (pp. 50â58), is a thorough review of the evidence for pre-exposure prophylaxis (PrEP), with either local (e.g. vaginal microbicides) or systemic (e.g. oral) use of antiretrovirals. Based on the positive results of several clinical trials, oral PrEP with Truvada [tenofovir disoproxil fumarate/emtricitabine (TTDF/FTC)] has now been approved by the United States Food and Drug Administration (FDA) to reduce risk of sexually acquired HIV infection in high-risk adults. Public health experts are struggling with how to translate scientific findings from PrEP effectiveness trials into real-world implementation. For several reasons PrEP cannot be seen in isolation from treatment, and thus deserves a place in this issue of Current Opinion in HIV and AIDS. First: the same drugs (TDF and FTC) that are used for PrEP are a mainstay of ART regimens (for this purpose lamivudine is considered similar to FTC), which is not an ideal situation considering the risk of HIV drug-resistance development. Second, both human and financial resources for the treatment scale-up are already limited; are we now going to spend resources on these relatively expensive drugs for prevention, while, in addition to the effect of HIV treatment on HIV transmission, other HIV prevention modalities are available (male and female condoms, male circumcision)? Hankins and Dybul carefully review the prerequisites for, challenges to and dilemma's of a PrEP rollout. They also briefly review exciting products in the pipeline, including long-acting agents. The cascade of HIV care, which has the ultimate aim to achieve and undetectable plasma viral load â for the benefit of the individual and to prevent onward transmission â goes way beyond âTest and Treatâ. It also involves linking people to care after a positive HIV test, retaining them in care, getting them to initiate ART (if they want so), and getting them to adhere to the treatment regimen. All assuming that the care given is adequate, and that the antiretrovirals are present every time and of good quality. In the eighth article of this issue, with the catchy title âPatching a Leaky Pipeâ, Kilmarx and Mutasa-Apollo (pp. 59â64) review the recent literature on these multiple Achillesâ heels of the treatment scale-up. Fixing just one or two is not enough: they can all work as âchain terminatorsâ. Carefully examining the gaps at each step of the cascade, country by country and community by community, will be among the most useful approaches for planers and decision makers to improve scale-up and quality of care â essential elements to reaching and keeping the 15 million on ART. Article number nine, by Samuel Oti (pp. 65â69), who has the privilege to work at the unique African Population and Health Research Centre in Nairobi, is a compassionate and well reasoned plea for a coordinated response to HIV and noncommunicable diseases (NCDs). It is amazing that the advantages of this are not yet evident to everyone. How can we defend testing every adult for HIV and not take a blood pressure measurement at the same time. Hypertension is the biggest risk factor for premature death in the world [4] and its treatment is relatively straightforward and affordable. To secure continued funding for HIV it is essential to show that this money adds value beyond HIV and helps to build viable and sustainable health systems. Last but not least, article number 10 in this issue, by ât Hoen and Passarelli (pp. 70â74), looks at the role of intellectual property rights in HIV treatment access. It is hard to understand for us, why thus far only one research-based pharmaceutical company (Gilead) has had the courage and common sense to contribute to the Medicines Patent Pool. What are the others afraid of and what do they want to accomplish? However, we are living in a rapidly changing world and access to medicines is a complex issue beyond licensing agreements. With significant economic growth in the developing world the old concepts of rich and poor countries are increasingly invalid. Already today, the significant majority of all people living with HIV is living in middle and high-income countries, up from less than one-third, 10 years ago. And this trend is to continue. We need new approaches to access and equity, differential pricing approaches that address poverty within a given country, more systematic approaches to price negotiations that protect the smaller and less powerful states in their attempts to negotiate access to life-saving medicines, and the full use of TRIPS flexibilities including compulsory licensing if we are to reach the 15 million, and beyond. All in all, although some pieces, like healthcare financing, are missing, this issue of Current Opinion in HIV and AIDS presents a relevant mix of articles about opportunities of and challenges to a continued antiretroviral therapy scale-up. It has been a privilege to have served as its editors. J.M.A.L. and B.S. Acknowledgements None. Conflicts of interest J.M.A.L. institution has been receiving educational grants from the following pharmaceutical companies: Abbott, Boehringer Ingelheim, Bristol Meyers Squibb (BMS), Crucell, Gilead, ViiV, Johnson and Johnson, Merck, Mylan, and Roche. I have received honoraria for speaking engagements or consulting from Bristol Meyers Squibb, Gilead, Roche and Tibotec (Johnson and Johnson). B.S. has no conflicts of interest.
Many successes have been achieved in HIV care in low- and middle-income countries (LMIC): increased number of HIV-infected individuals receiving antiretroviral treatment (ART), wide decentralization, reduction in morbidity and mortality and accessibility to cheapest drugs. However, these successes should not hide existing failures and difficulties. In this paper, we underline several key challenges. First, ensure long-term financing, increase available resources, in order to meet the increasing needs, and redistribute the overall budget in a concerted way amongst donors. Second, increase ART coverage and treat the many eligible patients who have not yet started ART. Competition amongst countries is expected to become a strong driving force in encouraging the least efficient to join better performing countries. Third, decrease early mortality on ART, by improving access to prevention, case-finding and treatment of tuberculosis and invasive bacterial diseases and by getting people to start ART much earlier. Fourth, move on from WHO 2006 to WHO 2010 guidelines. Raising the cut-off point for starting ART to 350 CD4/mm(3) needs changing paradigm, adopting opt-out approach, facilitating pro-active testing, facilitating task shifting and increasing staff recruitments. Phasing out stavudine needs acting for a drastic reduction in the costs of other drugs. Scaling up routine viral load needs a mobilization for lower prices of reagents and equipments, as well as efforts in relation to point-of-care automation and to maintenance. The latter is a key step to boost the utilization of second-line regimens, which are currently dramatically under prescribed. Finally, other challenges are to reduce lost-to-follow-up rates; manage lifelong treatment and care for long-term morbidity, including drug toxicity, residual AIDS and HIV-non-AIDS morbidity and aging-related morbidity; and be able to face unforeseen events such as socio-political and military crisis. An old African proverb states that the growth of a deep-rooted tree cannot be stopped. Our tree is well rooted in existing field experience and is, therefore, expected to grow. In order for us to let it grow, long-term cost-effectiveness approach and life-saving evidence-based programming should replace short-term budgeting approach.
OBJECTIVE: Scaling up antiretroviral treatment (ART) through decentralization of HIV care is increasingly recommended as a strategy toward ensuring equitable access to treatment. However, there have been hitherto few attempts to empirically examine the performance of this policy, and particularly its role in protecting against the risk of catastrophic health expenditures (CHE). This article therefore seeks to assess whether HIV care decentralization has a protective effect against the risk of CHE associated with HIV infection. DATA SOURCE AND STUDY DESIGN: We use primary data from the cross-sectional EVAL-ANRS 12-116 survey, conducted in 2006-2007 among a random sample of 3,151 HIV-infected outpatients followed up in 27 hospitals in Cameroon. DATA COLLECTION AND METHODS: Data collected contain sociodemographic, economic, and clinical information on patients as well as health care supply-related characteristics. We assess the determinants of CHE among the ART-treated patients using a hierarchical logistic model (n = 2,412), designed to adequately investigate the separate effects of patients and supply-related characteristics. PRINCIPAL FINDINGS: Expenditures for HIV care exceed 17 percent of household income for 50 percent of the study population. After adjusting for individual characteristics and technological level, decentralization of HIV services emerges as the main health system factor explaining interclass variance, with a protective effect on the risk of CHE. CONCLUSION: The findings suggest that HIV care decentralization is likely to enhance equity in access to ART. Decentralization appears, however, to be a necessary but insufficient condition to fully remove the risk of CHE, unless other innovative reforms in health financing are introduced.
Dermot Maher, Tido von Schoen-Angerer, Jennifer Cohn
The HIV epidemic is a leading global health challenge. While controversy has surrounded the best HIV prevention strategy, remarkable consensus has supported the campaign for universal access to antiretroviral therapy (ART) for people with HIV infection. As a necessary humane response to the epidemic, the moral imperative to provide ART to people with HIV infection has struck a chord of global solidarity. Much of the funding mobilised for the global response to HIV has supported successful expansion in ART access. Funding is now at a critical juncture as the global financial crisis bites and funders hesitate. Providing universal ART access is a steep hill only half climbed â faltering at this point risks rapid loss of recent gains, and the need to begin again an even steeper climb in future just to regain our current incomplete and perilous position. Against the background of overall efforts to roll back the HIV epidemic, we consider the implications of faltering finances for universal ART access and argue for additional funding, used efficiently. Progress towards universal ART access has individual and also potential community benefits. Although we focus mainly on sub-Saharan Africa as the region most badly affected by HIV and with the least resources to respond, other regions face similar issues. The seemingly inexorable rise in global HIV incidence during the first 30 years of the epidemic peaked towards the end of the 1990s. However, global HIV prevalence and deaths still remain at crisis levels, with 33.4 million people living with HIV and 2 million deaths in 2008 (1). The region most severely affected is sub-Saharan Africa, with 67% of HIV infections and 72% of HIV-related deaths worldwide in 2008 (1). Changing the course of an epidemic of a primarily sexually transmitted infection by changing sexual behaviour is difficult ââking sex is an unruly monarchâ. Demonstrating effectiveness and impact of behaviour change interventions has been difficult and there is little agreement on which specific interventions most effectively change behaviour. Male circumcision is one of few interventions shown in randomised trials to be effective in decreasing HIV transmission risk (2â4), but programmatic delivery is limited and long-term results are awaited. Thirty yearsâ advances in HIV virology and immunology have been a tremendous scientific success, but have not yet resulted in widely available HIV prevention technologies. The high variability of HIV envelope glycoproteins has frustrated attempts to develop an effective vaccine. After nearly 2 decades of research which failed to find an effective vaginal microbicide (5), the recent finding that tenofovir gel decreases risk of HIV acquisition by 39% is promising (6). Scientific advances have, however, resulted in widely applied HIV diagnosis and treatment technologies. Diagnostic HIV tests are widely available, rapid, easy-to-use, accurate and relatively cheap. Antiretroviral (ARV) drugs can effectively contain HIV even if a cure is not yet possible. Prolongation of life by ART â a tribute to science and technology â has transformed the previously bleak outlook for people with HIV infection. The impact of improved ART access on HIV-related mortality at the population level has been shown in countries with high income, e.g. UK (7) and low income, e.g. Malawi (8). The 10-fold expansion in access to ART in low- and middle-income countries over the 5 years up to 2007 is a tremendous achievement (9). However, the uphill task is not even half completed. The five million adults and children with HIV infection in low- and middle-income countries receiving ART by the end of 2009 represented only 36% of those in need (based on 2010 WHO guidelines) (9). This progress demonstrates proof of principle â that with political and financial commitment universal access to ART is possible â but an unfinished agenda remains. Faltering political and financial commitment threatens to stall progress towards universal ART access. Starting in 2008 the shock waves of the global financial crisis emanated quickly from the USA around the world. The myriad effects of the crisis include threats in developing countries to health services, including ART provision (much of which is funded by donors). The health infrastructure which has been painstakingly built up for ART provision can be easily dismantled in a funding downturn. Developed nations have responded to the âcredit crunchâ and the collapse of banking systems by allocating vast national resources to bail out financial institutions and industries while their economies contract. Under domestic pressure to curb spending, donor governments are cutting back on development assistance, which may account for a significant proportion of health service expenditure in developing countries. Developing country governments under fiscal constraint may also squeeze health sector expenditure. The global economic downturn therefore compounds the problems of diseases of poverty (e.g. HIV, tuberculosis and malaria) by a double whammy â as socioeconomic conditions which favour the spread of these diseases deteriorate, funds for the health sector response are restricted (10). After substantial yearly increases since 2002 in support for ART access, the USA and other donors have stalled in their funding commitments, with disbursements decreased for 2009 (11). Already by 2009 UNAIDS reported an adverse effect of the economic crisis on ART programmes (12). The Global Fund replenishment pledges for 2011â2013 reached $11.7 billion, far short of the $20 billion needed to expand programmes and even short of the $13 billion needed to keep existing programmes running (13). Although the latest WHO guidelines recommend a CD4 cell count of 350 cells/Îźl as a starting threshold for ART (14), many centres in Africa continue to use a threshold of 200 CD4 cells/Îźl because of insufficient ARV supply (15). Medecins sans Frontieres have reported ART rationing to the sickest patients in developing countries, directly contradicting the evidence of benefits of earlier treatment and WHO guidelines (16). Consequences of failure to maintain even the existing ARV drug supply include: more HIV-related diseases and deaths that could have been prevented; without treatment people becoming more infectious, with increased risk of transmission; and increased drug resistance generated by treatment interruption, necessitating more expensive second-line therapies to prevent HIV progression. Financially squeezed ART programmes may further compromise the quality of ART provision in Africa, where mortality is high in the first year of ART because of health systems delays in ART initiation and the quality of care (17). The funds invested in achieving the current level of ART access are a platform for further progress. Additional investment in progress towards universal ART access benefits people with HIV infection, and also potentially the community through improved HIV prevention and improved health systems. Early ART initiation improves patient outcomes and also reduces HIV infectiousness (18) and transmission (19,20), with the potential for âtreatment as preventionâ (21). Early ART with cessation of viral replication and subsequent immune restoration has benefits for the individual (less risk of HIV-related disease) and also potentially for public health (improved HIV prevention) and for society (increased productivity and decreased costs of HIV-related care) (22). The strategy of universal voluntary testing with immediate ART, which in a mathematical model could eliminate HIV transmission (23), needs evaluation in practice (24). Achieving universal ART access is easier if HIV incidence decreases. This is urgent as the rate of new HIV infections is greater than the rate that people with HIV start ART. Additional investments in implementing combined prevention interventions will decrease HIV incidence, thus facilitating ART provision. Progress towards universal and early ART access could become a virtuous cycle, as the more (and the earlier) that people start ART, the greater is the potential impact in decreasing transmission, with fewer incident cases and fewer people needing ART. Progress in ART provision requires investment in strengthened health systems as well as in the health system elements most directly involved in ART provision. The reasons why HIV has had a much greater impact in Africa than other regions include deficiencies in the regionâs health systems. Such deficiencies lead to failure to recognise emerging health problems, diagnose cases, provide quality care, manage surveillance, promote a safe healthcare environment and gain public confidence. Lack of preparedness increases vulnerability to future emerging health problems, unless health systems are strengthened using adequate resources. Investing in ART provision while strengthening health systems is a win-win situation for people with HIV infection and the community. Additional funding generated for improved ART access must be used more efficiently (25). In developing countries, a built-in cost-efficiency is that ARV drug costs fall as coverage increases. Proposals for maximising cost-efficiencies include a cross-cutting agenda for global health to meet the challenges of the financial crisis (26). Disease-specific health initiatives and funding programmes should agree on a cross-cutting agenda to reform the global health architecture and maximise cost-efficiencies, instead of advocating and competing for their own stake in the limited and diminishing pool of donor funds. At country level, greater integration of HIV and other programme activities, e.g. tuberculosis, could improve efficiency and strengthen health systems (27). Scaling-up home-based ART (28) and clinically driven rather than routine laboratory monitoring of ART side-effects (29) can improve ART programme efficiency. âHow to do more with lessâ is a research priority for extending ART access in low-resource settings (30). Finding efficiencies in healthcare delivery is important but does not replace sufficient, predictable financing by donors and domestic funding from low- and middle-income countries. Measures to ensure the lowest possible ARV drug prices facilitate cost-efficiencies. Changes in wealthy nationsâ trade policies are urgently needed to avoid creating new barriers for generic drugs. Generic competition has been critical to lowering drug costs and will be critical to also lower the prices of newer drugs needed for long-term survival (31). The free trade agreement with India pursued by the European Union, for example, will further increase monopoly protection, although India has already changed its patent law in compliance with World Trade Organization agreements (32). Donor countriesâ support for policies to contain ARV drug costs should complement their commitment to fund ART provision. Achieving universal access to ART is an uphill task but feasible if funding is increased and used efficiently. The choice is stark â to build on progress or to embrace defeat and consign the global movement for universal access to the fate of Sisyphus (33). Note: The views expressed by Dermot Maher are not necessarily those of the Medical Research Council (UK). We thank Brian Williams for his encouragement ââThe struggle itself towards the heights is enough to fill a manâs heartâ (Camus). DM is a clinical epidemiologist and researcher with extensive experience of the global HIV epidemic as a clinician, public health expert and field researcher. TvS-A has extensive experience of the global HIV epidemic and is a leading advocate on behalf of Medecins sans Frontieres for universal access to HIV prevention and treatment. JC has extensive experience of HIV/AIDS policy and advises the MĂŠdecins sans Frontières Campaign for Access to Essential Medicines. DM had the idea for the article which he developed in discussion with TvS-A and JC. DM took the lead in drafting the article and all authors contributed to the development of successive iterations. The sources of information for the article were relevant papers from the peer-reviewed literature. DM is guarantor for the article. TvS-A is employed by, and JC is a policy adviser to, the MĂŠdecins sans Frontières Campaign for Access to Essential Medicines, which advocates for universal access to HIV prevention and treatment.
Ongoing scale-up of HIV programs in an era of leveling funds for health require that each dollar is spent efficiently and effectively. From 2004 to 2009, the number of people on antiretroviral treatment (ART) grew from 700 000 to 5.2 million, with a 30% increase realized in 2009 alone [1]. At the same time, for every person starting therapy two others get infected, and the unmet need continues to grow. At the end of 2009, there were 9 million HIV-infected people who were eligible for ART but had not yet started treatment [2]. The Joint United Program on HIV/AIDS (UNAIDS) estimates that in 2009 US$ 15.9 billion was available for HIV/AIDS control globally, US$ 10 billion short of what was needed. There is also a recognized need to re-prioritize other areas of health, notably maternal and child care [3] and to reach universal health coverage [4]. Medium and long-term solutions require significant investment in health systems, increasing the money for health and maximizing health outcomes from available money [4]. As the level of international health financing stabilizes, high-HIV prevalence countries must increase HIV funding from domestic budgets [5], and continue to demonstrate the value for money of their AIDS response strategy to secure sustained donor funding [6,7]. Against this background of changing global health funding and priorities, HIV programs need to monitor and maintain the 5.2 million people currently on therapy, expand treatment initiations to people in earlier stages of infection according to WHO's 2010 guidance [8], and transition to less toxic but more expensive (tenofovir-based) antiretroviral regimens that may be more effective for chronic treatment [9]. Clear evidence on what works is vital for prioritizing program activities and budget allocations. The study by Phillips and colleagues [10] is timely to address the important question of the role of viral load monitoring in preventing the spread of antiretroviral drug resistance. Against the hypothesis that delaying the roll-out of viral load monitoring would result in a worldwide escalation of viral resistance, their modeling suggests that postponing the introduction of routine viral load monitoring will have limited consequences for resistance transmission: 12.4% of new HIV infections are predicted to have primary antiretroviral resistance in 2020 if clinical monitoring is used throughout, compared with 5.4 and 6.1% if viral load-guided switching were introduced in 2010 or 2015, respectively. Phillips and colleagues' findings strengthen the policy consensus and WHO recommendation â so far based on individual patient outcomes and cost-effectiveness in the shorter term [11,12] â that resource-poor countries need not delay ART roll-out because of limitations in laboratory capacity [13]. This is good news, especially for the next few years when HIV programs in many low-income settings are forced to ration new treatment initiations [14], and other ART-supportive activities such as patient adherence support remain underfunded [15]. In high HIV prevalence African countries where a viral load test costs $45â80 and overall delivery of first-line ART $600 per patient-year [12,16,17], omitting viral load monitoring (at one or two tests per year) would allow 8â27% more patients to initiate first-line therapy. In addition, routine viral load testing is associated with an average 40% increased rate of early switching to â more expensive â second-line regimens [18]. In the Phillips' model, introduction of viral load monitoring increased the proportion of patients on second-line regimens by four-fold after 10 years [10]. While improving health outcomes by a small extent [11,12], viral load testing might therefore indirectly increase the average cost per patient by 20â40% or more [19]. Reports by National AIDS programs to the WHO and UNAIDS show large variations in patient monitoring strategies, in rates of switching to second-line regimens, as well as in expenditures per patient [1,2,20]. Several middle-income countries such as Brazil use 3-monthly CD4 and viral load monitoring and a large number of first-line and second-line regimens. Low-income country Malawi, in contrast, implements the WHO-recommended Public Health approach [13], relying on clinical patient monitoring alone and providing a minimum set of WHO-recommended antiretroviral regimens [17]. The marked reductions in AIDS deaths documented in Malawi within years of its ART roll-out since 2004 [20,21] illustrate what can be achieved under a highly simplified medicinal and patient monitoring approach. Delaying the introduction of routine viral load monitoring is in keeping with UNAIDS' Treatment 2.0 strategy [22], an extension on WHO's Public Health approach that aims to further simplify delivery and improve effectiveness of ART. An improved profile of antiretroviral regimens (one pill a day containing a regimen that is forgiving of suboptimal adherence and nontoxic, thus minimizing the need for laboratory monitoring) should allow decentralized community-based treatment delivery. The strategy also promotes an enhanced focus on HIV testing, and on linking treatment delivery with behavioral change communication, to maximize prevention effects. Whereas the antiretroviral regimens envisaged for Treatment 2.0 remain to be developed, ongoing evaluation of the program performance and health impact of public health ART approaches such as in Malawi and Uganda [23] should critically inform global policies. In 2011, Malawi will adopt the WHO recommendation to initiate ART at a CD4 threshold of 350 cells/Îźl, and transition to tenofovir-based first-line regimens â while for the moment maintaining its practice of minimum patient laboratory monitoring [17]. As patients accumulate years on ART, notably when started at higher CD4 cell counts, longer-term health outcomes and viral resistance surveillance [2,24] will also prove or disprove model predictions â which remain a main guidance at the moment. In the long term, ART programs should aim to expand routine viral load monitoring to prevent viral resistance and preserve the effectiveness of antiretroviral regimens. This will become more affordable and more cost-effective as prices of viral load tests and of second-line antiretroviral drugs continue to decrease. In the short term, while high-prevalence countries continue prioritizing the roll-out of HIV testing and counseling and ART initiations, supportive interventions could focus on effective antiretroviral procurement and distribution to minimize health system-induced treatment interruptions, and on patient adherence support to improve retention and survival on first-line regimens [2,24â26].
Kathryn Church, Korrie de Koning, Adriane Martin Hilber, Hermen Ormel ¡ 5 authors
Current attempts to address the high burden of sexual health morbidity and mortality in developing countries remain limited in scale due to a range of health system constraints. We conducted a literature review of the policy and programmatic issues that influence the integration of sexual health into primary care services in developing countries. Forty-seven reports were identified from a search of both peer-reviewed and gray literature. Key issues identified were intersectoral and intergovernmental coordination; management and organizational issues including decentralization, health sector reform, logistics, and referral systems; human resources, including training and support required to increase service scope; relationships between the public and private sectors; and scaling-up and financing issues.
David Katzenstein, Sinata KoullaâShiro, Marie Laga, JeanâPaul Moatti
The extraordinary success of antiretroviral therapy (ART) in the North during the closing years of the last century directly led to the United Nations' resolutions in 2000, about universal access to HIV treatment, and to the inclusion of this target among the Millenium Development Goals [1]. A previous AIDS supplement, supported by the French Agency for AIDS Research (ANRS) and published as early as 2003, presented the evaluation of the first national pilot programs for access to antiretroviral HIV treatment in three African countries (CĂ´te d'Ivoire, Senegal and Uganda). These results contributed to a consensus on the feasibility of scaling-up access to HIV treatment in low-resource settings, an issue that had been heavily debated among clinical, public health and development experts [2]. Since then, antiretroviral therapy coverage rose from 7% in 2003 to 42% in 2008, with especially high coverage achieved in eastern and southern Africa (48%) [3]. There are no longer doubts that access to ART results in a remarkable reduction in mortality, which may be as high as 95% in comparison to no intervention [4]. In addition, retention in care and treatment may exceed levels seen in the North: for example, a remarkable 79% of adults enrolled in the early stages of Botswana's antiretroviral therapy scale-up are alive five years later [5]. On a macro scale, Bendavid and Bhattacharya [6] found that after four years of the US President's Emergency Plan for AIDS Relief (PEPFAR) funding and support for ART, HIV-related deaths decreased in sub-Saharan African focus countries compared with control countries, although trends in adult prevalence did not differ. Despite the community stigma, political denial and tensions between government policy and medical practice, South Africa with the largest number of HIV infected individuals is also home to the largest antiretroviral therapy program in the world with accelerating impact. In the Western Cape Province, six-month mortality among patients at an HIV treatment centre fell from 12.7% to 6.6% between 2001/2002 and 2005 as access expanded [7]. The recent statement, on World AIDS Day on December 1st 2009, about universal access to HIV care and treatment by the new South-African President, Jacob Zuma, raises hope that South Africa will henceforth assume a leadership role in the region [8]. However, scaling-up access to HIV treatment in Africa, home to two thirds of those living with HIV/AIDS, poses new and largely unexplored challenges in the delivery of a complex set of public health, medical and psychosocial interventions. The transition from an emergency response to robust and sustainable health services delivery systems for HIV is a work in progress. Building these systems must be mindful of cultural context and existing health systems in the affected communities. The most recent [9] report on the epidemic describes a highly varied picture of remarkable progress in some African countries and huge unmet needs in others. Access to treatment in Africa is often taking place in the context of fragile states, struggling with social, political and economic turmoil, where investment in healthcare systems has been limited. Particularly in resource limited settings, there is an unavoidable competition for infrastructure, resources and personnel between donor driven programs targeting specific diseases (ie. AIDS, TB and malaria) and long standing programs in primary care, maternal and infant health. The âMaximizing Positive Synergies Collaborative Groupâ (MPSCG), coordinated by WHO, has recently synthesized the existing evidence regarding interactions between disease-targeted programs and country health systems [10]. Although it concluded that this impact âon health outcomes and health systems, though variable, has been positive on balance and has helped to draw attention to deficiencies in health systemsâ, available evidence also pointed out that further improvements and efficiency gains are needed especially to strengthen the health workforce, align health information systems, and to reduce out-of-pocket payments for financing health-care expenditures. Operational research encompasses a broad range of investigation, primarily the evaluation of outcomes among the health programs. Systematic observation and analysis of data collected alongside ART programs can provide guidance to implementers and policy makers with the aim of achieving sustainable access to care. Critical in any operational research project is the development of partnerships and capacity building between the wide array of actors who contribute to deliver healthcare, including national health services, community based organizations and advocacy groups, national and transnational NGOs, as well as the international donor agencies on the one hand, and academic researchers and research organizations on the other [11]. There are certainly general principles of treatment that can be broadly applied and evaluated in Africa. But ultimately, in each context, it may be anticipated that the design of programs for access to ART will vary. Critical unanswered questions remain about how access to ART will impact social stigma, individual risk behavior and ultimately the course of the epidemic. Because of the heterogeneity of affected populations and societies, the psychosocial and behavioral consequences of ART access and methods to ensure adherence, retention and to provide sustained treatment across Africa are not likely to be distilled to a single set of best practices. Thus, in the face of the HIV epidemic in Africa, operational research is a process of âlearning by doingâ in each of the diverse contexts, sharing the outcomes and observations among countries and programs. A myriad of local evaluations of process and outcome may be the most flexible way to effect sustainable implementation of ART access and the development of robust medical and social responses to AIDS in various contexts across a continent. One regrets that in spite of significant investment in evaluation exercises, global health initiatives such as the Global Fund to fight AIDS, Tuberculosis and Malaria (GFATM), PEPFAR or the World Bank still have limited contributions to effective operational research [12,13]. Operational issues in scaling up access to ART This supplement presents original results documenting the progress, as well as obstacles, in scaling up HIV treatment in Africa. Papers from Burkina-Faso and Cameroon are based on operational research carried out alongside the national ART programs of these two countries that have been directly supported by ANRS. Other papers present fruitful experiences from operational research in additional African countries (Botswana, Lesotho, Mozambique and South Africa) while one paper (Celletti et al., S45âS57) focuses on a multi-country effort associating four African countries (Ethiopia; Malawi; Namibia and Uganda) and Brazil. It must be noted that the paper by Bassett et al. (S37âS44) about initiation of ART in Durban, Kwazulu-Natal, South Africa, one of the epicenters of the epidemic, was awarded the joint International AIDS Society (IAS)/ ANRS âYoung Investigator Prizeâ for Operations Research at the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, that took place in Capetown in July 2009. Finally, one paper (Jerome & Ivers, S73âS78) deals with rural Haiti, a non-African country, whose experience with ART in very deprived and vulnerable populations has been worthwhile for other low-resource settings. The process of improving and sustaining access to ART begins with surveillance and testing to understand the magnitude of the epidemic locally, and requires assessment and consultation with Ministries, healthcare providers, communities and stakeholders to identify the key operational issues in access. Access to ART begins with the effective implementation of voluntary testing on a scale not yet realized, effective post-test counseling, linkage to care, and has already led to monitoring, care and retention of 3 million people on ART in Africa. How to accomplish each of these tasks with health systems that are often insolvent and frequently understaffed is the focus of the papers presented in this supplement. All papers emphasize that advances in access to ART have only been made possible through implementation of innovative ways of delivering and monitoring care, and also illustrate some of these innovations. Clinical research programs continue to evaluate new, less toxic and potentially less costly drug cocktails, more effective monitoring algorithms and programs to reinforce and maintain treatment adherence that would be better adapted to the practical constraints of health systems with very scarce resources. Notably, the DART study results in Uganda and Zimbabwe suggest that some of the accepted guidelines for laboratory monitoring need careful reassessment [14], and the forthcoming results of the STRATALL study in Cameroon will evaluate the impact of the WHO public health approach to monitor ART at a decentralized level of care [15]. Similarly, the management of first-line ART is fraught with issues even in the choice of Non-nucleoside reverse transcriptase inhibitors (NNRTIs). Consideration of Efavirenz and Nevirapine as first line NNRTIs as described in the paper by Wester et al. (S27âS36) in Botswana reflect trade-offs among cost, potency, potential side-effects and concerns about teratogenicity and toxicity. These issues will continue to expand as additional drugs become available and as the price proposed by pharmaceutical firms for new first-line and for second-line regimens, as recommended by WHO, remain prohibitively high compared to those of the âoldâ generation of antiretroviral drugs [16]. It is estimated that at least 57 countries, mostly in sub-Saharan Africa, face crippling health workforce shortages, and there are simply not enough physicians and nurses on the ground to begin to address the magnitude of the HIV epidemic through traditional clinic based care. Rational redistribution of tasks between physicians and other healthcare personnel, and the introduction of community and family health aids and NGO volunteers, as medical officers, adherence counselors or treatment âbuddiesâ is a key part of the âtask-shiftingâ agenda articulated by WHO [17]. The multi-country paper by Celletti et al. (S45âS57), papers by Sherr et al. (S59âS66) on Mozambique, Jerome and Ivers (S67âS72) on Haiti and Ivers et al. (S73âS78) on the Haiti-Lesotho collaborative model detail the certain conditions that have to be fulfilled for the reorganization of clinical services under a task shifting model to be successful. One of the most innovative contributions of HIV programs has been to promote meaningful multi-stakeholder partnerships between governments, civil society and affected communities at the global and local levels. Civil society has critically important roles ranging from advocacy, demand creation, and service delivery, to policy-setting and providing oversight by emphasizing accountability to service users [18]. Papers by Desclaux et al. (S79âS85) on Burkina-Faso and Ivers et al. (S73âS78) on the south-south collaboration between Haiti and Lesotho illustrate how such involvement of civil society offer opportunities for creative operational research. Quite logically, it is the relationship between scaling up access to HIV treatment and health systems strengthening that bears the greatest scrutiny across most of the papers of this supplement. In a comprehensive evaluation of ART access through a national program in Cameroon, Boyer et al. (S5âS15) present analysis from the EVAL study where the quality and quantity of care at central, provincial and district levels was contrasted. This evaluation clearly shows that decentralization of ART delivery can increase equity in access for the poorest sectors of people living with HIV while maintaining clinical effectiveness, and even improving adherence and quality of life. Experiences in other African countries, like Uganda, suggest that even further decentralization of ART may be effective and cost-effective [19], but this needs more investigation and may differ according to each specific socio-economic and health systems context. Future challenges for long term sustainability of ART In this supplement, another paper on Cameroon by Marcellin et al. (S17âS25) provides compelling evidence that access to ART at higher CD4 levels reduces reported risk behaviors and can improve quality of life. This paper, and the one from Bassett et al. (S37âS44) describing considerable gaps in bringing and retaining people with AIDS into treatment in a well resourced program in South Africa, supports the recent revision of WHO guidelines [20]. These new guidelines increase the recommended CD4 count for starting treatment to 350 cc/mm3 (rather than the previous lower 200 threshold) and imply that an additional number of 5 million HIV-infected patients world-wide should be considered eligible for immediate access to ART. These papers, however, anticipate some of the new challenges and tensions that would logically derive from this extension of treatment eligibility and from the urgent need to revisit the relationship between HIV prevention and treatment. Despite the actions of many agencies and national health autorities, an estimated 1.9 million [1.6 millionâ2.2 million] new HIV infections occurred in sub-Saharan Africa in 2008. This high incidence, and consequent increase in unmet treatment needs over time, represents an additional key challenge for ART program scale up to remain feasible and sustainable [21]. The recognition that the speed at which people are infected exceeds the speed at which they can be put on treatment has been a powerful message to advocate for enhancing prevention efforts. Treatment programs offer many opportunities to strengthen prevention, through increased uptake of testing, viral load reduction in patients and models of âprevention counselingâ for and by positive people. These synergies should be fully recognized and monitored. As an illustration, in a paper on Cameroon in this supplement (Marcellin et al. [S17âS25]), patients not yet on ART reported more frequent inconsistent condom use compared to those on ART, confirming positive effects of intense patient-healthcare worker contact on behavior. (Re)-emphasizing and maximizing synergies between the ART roll out and prevention is essential and urgent but should be seen as a component of a comprehensive âTreatment and Prevention Combinationâ approach, including behavioral, social and structural interventions. Over the coming decade, the challenges of expanding, enhancing and sustaining treatment for the more than 22.4 million people living with HIV in Africa, will consume immense monetary, human and social resources. Evaluating the long-term outcomes of access to ART on a population level across diverse urban and rural and multiple cultural contexts in Africa present a formidable challenge. If the patterns of behavior and transmission observed in the North are any indication, large-scale access to care may increase transmission of drug resistant viruses [22]. The best way to prevent this will be the development of robust and affordable programs for retention, monitoring and management of ART by skilled providers and robust systems of care. Papers in this supplement support the optimistic view that innovative solutions can be found to tackle the multiple medical, public health, socio-economic and logistic issues related to long term sustainability of ART programs in Africa. Ensuring their financial sustainability through appropriate growth of domestic and international funding however remains a prerequisite for success, and this is far from guaranteed in the context of one of the worst economic crises the world has ever faced. Because overall demand has been higher than anticipated in the funding scenario of its previous replenishment, the Global Fund faces a resource gap for the period 2009â10 for the first time since its creation. Its future contribution to scaling up the response to the HIV epidemic will depend on the willingness of donor governments to provide significantly higher pledges for its next replenishment (2011â2013) than the 9.8 billion US$ obtained for the previous one (2008â2010) [23]. In the US, a debate is growing about whether or not a further expansion of PEPFAR would be the best use of international health funding [24]. Demonstrations, as presented in this supplement, contribute evidence-based advocacy in favor of sustainability of HIV/AIDS treatment and provide clear examples of how health systems are adapting to meet the challenges of HIV. Of course, we also present these examples to underscore the importance of continuing, flexible operational research and evaluation to maintain international and domestic funding, the life-blood of treatment access for millions in Africa, and around the world.
Sylvie Boyer, Fred Eboko, Mamadou Camara, Claude AbÊ ¡ 7 authors
BACKGROUND: The independent evaluation of the Cameroonian antiretroviral therapy (ART) Programme, which reached one of the highest coverage in the eligible HIV-infected population (58%) in Sub-Saharan Africa, offered the opportunity to assess ART outcomes in the context of the decentralization of HIV care delivery. MATERIALS AND METHODS: A cross-sectional survey (EVAL, ANRS 12-116, 2007) was carried out in a random sample of 3151 HIV-positive patients (response rate 90%) attending 27 treatment centres at the different level of the healthcare delivery (central, provincial and district), as well as in the exhaustive sample of doctors in charge of HIV care in these centres (response rate 92%, n = 97). Multivariate two-level analyses were conducted to assess the impact of the level of healthcare delivery on CD4 cell gains since initiation of treatment and adherence to treatment in the subsample of patients who were ART-treated for 6 months or more (n = 1985). RESULTS: District treatment centres were characterized by more limited technical and human resources but a lower workload. ART-treated patients followed up in these centres had significantly lower socioeconomic status. After adjustment for other explanatory factors, immunological improvement was similar in patients followed up at the central and district level, whereas adherence to ART was better both at provincial and district levels. CONCLUSION: Success in scaling-up access to ART in Cameroon has been facilitated by decentralization of the healthcare system. Long-term sustainability urgently implies better integration of this HIV-targeted programme in the global healthcare reform of financing mechanisms, management of human resources and drug procurement systems.
As of July 1994, there were 565,856 human immunodeficiency virus (HIV)-infected persons in South Africa, half of whom were 18-25 years of age, and 27% of the adult population is likely to be infected by the year 2010 if current risk behaviors persist. By 2005, the cost of acquired immunodeficiency syndrome (AIDS) to South Africa's health service could reach R18 billion. The newly established National AIDS Task Force seeks to prevent further HIV transmission by promoting condom use, improving control of sexually transmitted diseases, providing a safe blood supply, adopting universal precautions for skin piercing and surgical procedures, preventing intravenous drug use, providing information about prenatal transmission, promoting policies that raise women's status, and socioeconomic development. The personal and social impact of HIV infection will be ameliorated through comprehensive health care and counseling for AIDS victims and their families, protection of infected individuals from discriminatory practices, sustainable social services and benefits to meet the needs of those with AIDS, and promotion of policies that address the socioeconomic consequences of AIDS. On the administrative level, interventions are planned to promote intersectoral coordination, ensure adequate financing, promote community involvement, decentralize planning and management, ensure program monitoring and evaluation, forecast HIV trends, and share technical expertise.
The costs of the medical care needs of AIDS patients are well above the average per capita expenditure on health care in many sub-Saharan African countries. These costs may become completely unaffordable as specific anti-viral drugs come onto the market, and the burden will fall on health networks, whose present strained budgets show no real signs of increase. In addition, pilferage, mismanagement and inefficiency continue at the few existing hospitals. As the total number and percentage of hospitalized patients with AIDS increases, the hospital networks (and the health services as a whole) risk collapse. The risks are of the same magnitude for both rural and urban hospitals - the former will not be able to deliver the necessary minimum quality of clinical standards, the latter will be flooded by too many patients. Achieving reasonable standards of hospital management and decentralization of curative care are critical targets for at least avoiding the risk that donors may be unwilling to finance specific anti-HIV drugs for these poor (and high-prevalence) countries.