HIV This Week

Factors influencing global antiretroviral procurement prices.

Wirtz VJ, Forsythe S, Valencia-Mendoza A, Bautista-Arredondo S. BMC Public Health. 2009. 9 Suppl 1:S6.

Antiretroviral medicines are one of the most costly parts of HIV treatment. Many countries are struggling to provide universal access to antiretroviral medicines for all people living with HIV. Although substantial price reductions of antiretroviral medicines have occurred, especially between 2002 and 2008, achieving sustainable access for the next several decades remains a major challenge for most low- and middle-income countries. The objectives of the present study were twofold: first, to analyze global antiretroviral prices between 2005 and 2008 and associated factors, particularly procurement methods and key donor policies on antiretroviral procurement efficiency; second, to discuss the options of procurement processes and policies that should be considered when implementing or reforming access to antiretroviral treatment programs. An antiretroviral medicines price-analysis was carried out using the Global Price Reporting Mechanism from the World Health Organization. For a selection of 12 antiretrovirals, global median prices and price variation were calculated. Linear regression models for each antiretroviral were used to identify factors that were associated with lower procurement prices. Logistic regression models were used to identify the characteristics of those countries which procure below the highest and lowest direct manufactured costs. Three key factors appear to have an influence on a country’s antiretroviral prices: (a) whether the product is generic or not; (b) the socioeconomic status of the country; (c) whether the country is a member of the Clinton HIV/AIDS Initiative. Factors which did not influence procurement below the highest direct manufactured costs were HIV prevalence, procurement volume, whether the country belongs to the least developed countries or a focus country of the United States President’s Emergency Plan for AIDS Relief. One of the principal mechanisms that can help to lower prices for antiretroviral medicines over the next several decades is increasing procurement efficiency. Benchmarking prices could be one useful tool to achieve this.

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Editors’ note: There has been an unprecedented global effort to increase antiretroviral drug price transparency, including through the requirements of the Global Fund, the Clinton Initiative, and others for countries to report their pricing data. The Global Price Reporting Mechanism (GPRM) provides information on the prices that countries actually paid for antiretroviral medications through its publicly accessible database http://www.who.int/hiv/amds/gprm/en/. Analysis of the GPRM data debunks the assumptions that procuring larger volumes will reduce prices (that was true for only 2 of the 12 drugs studied) and that generic competition leads to equivalent innovator prices (only the second line innovator product lopinavir/ritonavir was associated with lower prices than generic products). Since there is tiered pricing or discounts for most antiretroviral drugs bought by low- and low-middle-income countries, with the exception of the entry inhibitor maraviroc, continued expansion of the GPRM to include data from all countries will increase long-term efficiency (best value for money) in antiretroviral drug procurement.

Galárraga O, Colchero MA, Wamai RG, Bertozzi SM. BMC Public Health. 2009. 9 Suppl 1:S5.

After more than 25 years, public health programs have not been able to sufficiently reduce the number of new HIV infections. Over 7,000 people become infected with HIV every day. Lack of convincing evidence of cost-effectiveness may be one of the reasons why implementation of effective programs is not occurring at sufficient scale. This paper identifies, summarizes and critiques the cost-effectiveness literature related to HIV-prevention interventions in low- and middle-income countries during 2005-2008. Systematic identification of publications was conducted through several methods: electronic databases, internet search of international organizations and major funding/implementing agencies, and journal browsing. Inclusion criteria included: HIV prevention intervention, year for publication (2005-2008), setting (low- and middle-income countries), and cost-effectiveness estimation (empirical or modeling) using outcomes in terms of cost per HIV infection averted and/or cost per disability-adjusted life year(DALY) or quality-adjusted life year (QALY). The authors found 21 distinct studies analyzing the cost-effectiveness of HIV-prevention interventions published in the past four years (2005-2008). Seventeen cost-effectiveness studies analyzed biomedical interventions; only a few dealt with behavioural and environmental/structural interventions. Sixteen studies focused on sub-Saharan Africa, and only a handful on Asia, Latin America and Eastern Europe. Many HIV-prevention interventions are very cost effective in absolute terms (using costs per DALY averted), and also in country-specific relative terms (in cost per DALY measured as percentage of GDP per capita). There are several types of interventions for which cost-effectiveness studies are still not available or are insufficient, including surveillance, abstinence, school-based education, universal precautions, prevention for positives and most structural interventions. The sparse cost-effectiveness evidence available is not easily comparable; thus, not very useful for decision making. More than 25 years into the HIV epidemic and billions of dollars of spending later, there is still much work to be done both on costs and effectiveness to adequately inform HIV prevention planning.

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Editors’ note: Cost-effectiveness analyses in HIV prevention can provide part of the information that decision-makers use to decide on the optimal mix of interventions to tailor to their epidemic context. Although available cost-effectiveness data show that many HIV prevention interventions are cost-effective, there are huge gaps in our knowledge. For example, there are no cost-effectiveness studies on prevention for and with positive people, for key populations at higher risk of HIV exposure in concentrated epidemics around the world, and for inmates or other captive populations. We lack cost-effectiveness data by epidemic type and scale-up scenario, as well as for a number of HIV prevention interventions that are considered standard components of national strategies. Cost-effectiveness analysis has several limitations and is not the ‘be all, end all’ in decision-making but it can usefully inform difficult choices.

Rethinking the conceptual terrain of AIDS scholarship: lessons from comparing 27 years of AIDS and climate change research.

Chazan M, Brklacich M, Whiteside A. Global Health. 2009;5:12.

While there has recently been significant medical advance in understanding and treating HIV, limitations in understanding the complex social dimensions of HIV epidemics continue to restrict a host of prevention and development efforts from community through to international levels. These gaps are rooted as much in limited conceptual development as they are in a lack of empirical research. In this conceptual article, the authors compare and contrast the evolution of climate change and AIDS research. They demonstrate how scholarship and response in these two seemingly disparate areas share certain important similarities, such as the “globalization” of discourses and associated masking of uneven vulnerabilities, the tendency toward techno-fixes, and the polarization of debates within these fields. They also examine key divergences, noting in particular that climate change research has tended to be more forward-looking and longer-term in focus than AIDS scholarship. Suggesting that AIDS scholars can learn from these key parallels and divergences, the paper offers four directions for advancing AIDS research: focusing more on the differentiation of risk and responsibility within and among AIDS epidemics; taking (back) on board social justice approaches; moving beyond polarized debates; and shifting focus from reactive to forward-looking and proactive approaches.

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Editors’ note: In the lead up to Copenhagen, this article makes for a very stimulating read. You will learn about the similarities and differences between HIV and climate change research but also about how the response to these two threats was conceptualised at different time periods. Both phenomena are complex, unprecedented, and highly dynamic. For both, scholarship has evolved from a physical or life sciences perspective to one that integrates the social sciences. HIV researchers can learn from the forward-looking and longer-term focus of climate change research, along with its well-considered social vulnerability concepts. A strong message emerges: we need to intervene now proactively to identify and address existing context-specific vulnerabilities to HIV infection and AIDS impacts, before HIV epidemics have fully run their course, in order to mitigate future impacts. It means moving away from a crisis footing to a forward-looking proactive stance to understand was is needed now to reduce or prevent future hardships.

Hecht R, Bollinger L, Stover J, McGreevey W, Muhib F, Madavo CE, de Ferranti D. Health Aff (Millwood). 200 ;28:1591-605.

The HIV pandemic will enter its fiftieth year in 2031. Despite much progress, there are thirty-three million infected people worldwide, and 2.3 million adults were newly infected in 2007. Without a change in approach, a major pandemic will still be with us in 2031. Modelling carried out for the AIDS 2031 project suggests that funding required for developing countries to address the pandemic could reach $35 billion annually by 2031-three times the current level. Even then, more than a million people will still be newly infected each year. However, wise policy choices focusing on high-impact prevention and efficient treatment could cut costs by half. Investments in new prevention tools and major behaviour-change efforts are needed to spur more rapid advances. Existing donors, middle-income countries with contained epidemics, philanthropists, and innovative financing could help bridge the likely funding gap.

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Editors’ note: Looking at what might be done differently to alter significantly the course of the HIV pandemic in order to achieve by 2031 few new infections, nearly all those in need of treatment receiving it, and children orphaned by AIDS assisted to lead normal lives, this costs and financing group lays out some stark choices. Modelling of four scenarios – rapid scale-up, current trends, hard choices for prevention, and structural change – reveals that at best 1 million new adult infections will occur in 2031. The ‘game-changers’, while waiting for a vaccine or cure, are high reach, effective prevention programmes for people who inject drugs, men who have sex with men, people who sell sexual services, and increasing numbers of discordant couples as the epidemic matures. Anticipating that resource requirements are set to increase rapidly over the next 5 to 8 years, six policy actions are described to expand financing for HIV in low- and middle-income countries. This is a sobering but essential read for us all.

The effects of global health initiatives on country health systems: a review of the evidence from HIV/AIDS control.

Biesma RG, Brugha R, Harmer A, Walsh A, Spicer N, Walt G. Health Policy Plan. 2009; 24:239-52.

This paper reviews country-level evidence about the impact of global health initiatives, which have had profound effects on recipient country health systems in middle- and low- income countries. Biesma and colleagues have selected three initiatives that account for an estimated two-thirds of external funding earmarked for HIV control in resource-poor countries: the Global Fund to Fight AIDS, TB and Malaria, the World Bank Multi-country AIDS Program (MAP) and the US President’s Emergency Plan for AIDS Relief (PEPFAR). This paper draws on 31 original country-specific and cross-country articles and reports, based on country-level fieldwork conducted between 2002 and 2007. Positive effects have included a rapid scale-up in HIV service delivery, greater stakeholder participation, and channelling of funds to non-governmental stakeholders, mainly NGOs and faith-based bodies. Negative effects include distortion of recipient countries’ national policies, notably through distracting governments from coordinated efforts to strengthen health systems and re-verticalization of planning, management and monitoringand evaluation systems. Sub-national and district studies are needed to assess the degree to which global health initiatives are learning to align with and build the capacities of countries to respond to HIV; whether marginalized populations access and benefit from global health initiatives-funded programmes; and about the cost-effectiveness and long-term sustainability of the HIV programmes funded by the global health initiatives. Three multi-country sets of evaluations, which will be reporting in 2009, will answer some of these questions.

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Editor’s note: Global health initiatives are defined as ‘ a blueprint for financing, resourcing, coordinating and/or implementing disease control across at least several countries in more than one region of the world’. They may be bilateral (e.g. US PEPFAR), multilateral (e.g. World Bank MAP), or public-private partnerships (Global Fund) aid mechanisms. This first systematic review of published and unpublished reports from 2002 to 2007 examines the effects of these three initiatives on national policy; coordination and planning; stakeholder involvement; disbursement, absorptive capacity, and management; monitoring and evaluation; and human resources. It suggests that these initiatives, each with different effects, initially often had negative effects, revealing country system weaknesses. As lessons were learned, the effects on health systems were more positive. The principal recommendations of this review are first, that global health initiatives, recipient donor countries, civil society organisations, and technical agencies alike should engage more fully with the Paris Principles for AIDS Effectiveness. Secondly, country and global policy makers and donors should demand and fund the acquisition of better evidence, including more analytical health policy and health systems evaluation. This article should be very high on your reading list!

Sanjana P, Torpey K, Schwarzwalder A, Simumba C, Kasonde P, Nyirenda L, Kapanda P, Kakungu-Simpungwe M, Kabaso M, Thompson C. Hum Resour Health. 2009 ;7:44.

The human resource shortage in Zambia is placing a heavy burden on the few health care workers available at health facilities. The Zambia Prevention, Care and Treatment Partnership began training and placing community volunteers as lay counsellors in order to complement the efforts of the health care workers in providing HIV counselling and testing services. These volunteers are trained using the standard national counselling and testing curriculum. This study was conducted to review the effectiveness of lay counsellors in addressing staff shortages and the provision of HIV counselling and testing services. Quantitative and qualitative data were collected by means of semistructured interviews from all active lay counsellors in each of the facilities and a facility manager or counselling supervisor overseeing counselling and testing services and clients. At each of the 10 selected facilities, all counselling and testing record books for the month of May 2007 were examined and any recordkeeping errors were tallied by cadre. Qualitative data were collected through focus group discussions with health care workers at each facility. Lay counsellors provide counselling and testing services of quality and relieve the workload of overstretched health care workers. Facility managers recognize and appreciate the services provided by lay counsellors. Lay counsellors provide up to 70% of counselling and testing services at health facilities. The data review revealed lower error rates for lay counsellors, compared to health care workers, in completing the counselling and testing registers. Community volunteers, with approved training and ongoing supervision, can play a major role at health facilities to provide counselling and testing services of quality, and relieve the burden on already overstretched health care workers.

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Editors’ note: Zambia is more than an order-of-magnitude (10 times) below the recommended staff-to-population ratios for nurses (1:700 versus 1:8064) and pharmacists (1:8000 versus 1:473,000), spurring it on to find solutions to this health care bottleneck. A two-week classroom component followed by a four-week supervised practicum and training in finger-prick HIV testing has created a cadre of lay counsellors providing quality services to satisfied clients. Some lay counsellors view reducing stigma and representing community role models as additional responsibilities. The fact that this is a voluntary programme (lay counsellors receive 25USD per month to defray travel costs but no other compensation) may jeopardise its sustainability. Continued supervision of the work of these lay counsellors, along with formalisation of their relationship with health facilities, could enhance both performance and retention. 

Makwiza I, Nyirenda L, Bongololo G, Banda T, Chimzizi R, Theobald S. Who has access to counselling and testing and anti-retroviral therapy in Malawi – an equity analysis. Int J Equity Health. 2009;8(1):13.

The HIV epidemic in Malawi poses multiple challenges from an equity perspective. It is estimated that 12% of Malawians are living with HIV among the 15-49 age group. This paper synthesises available information to bring an equity lens on counselling and testing and antiretroviral therapy policy, practice and provision in Malawi. A synthesis of a wide range of published and unpublished reports and studies using a variety of methodological approaches was undertaken. The analysis and recommendations were developed, through consultation with key stakeholders in Malawi. At the policy level Malawi is unique in having an equity in access to antiretroviral therapy policy, and equity considerations are also included in key counselling and testing documents. The number of people accessing counselling and testing has increased considerably from 149,540 in 2002 to 482,364 in 2005. There is urban bias in provision of counselling and testing and more women than men access counselling and testing. Antiretroviral therapy has been provided free since June 2004 and scale up of antiretroviral therapy provision is gathering pace. By end December 2006, there were 85,168 patients who had ever started on antiretroviral therapy in both the public and private health sector, 39% of the patients were male while 61% were female. The majority of patients were adults, and 7% were children, aged 14 years or below. Despite free antiretroviral therapy services, patients, especially poor rural patients, face significant barriers in access and adherence to services. There are missed opportunities in strengthening integration between counselling and testing and antiretroviral therapy and tuberculosis, sexually transmitted infections, and maternal health services. To promote equitable access for counselling and testing and antiretroviral therapy in Malawi there is need to further invest in human resources for health, and seize opportunities to integrate counselling and testing and antiretroviral therapy services with tuberculosis, sexually transmitted infection and maternal health services. This should not only promote access to services but also ensure that resources available for counselling and testing and antiretroviral therapy strengthen rather than undermine the provision of the essential health package in Malawi. Ongoing equity analysis of services is important in analyzing which groups are unrepresented in services and developing initiatives to address these. Creative models of decentralization, whilst maintaining quality of services are needed to further enhance access of poor rural women, men, girls and boys.

Editors’ note: Although only 43% of Malawians in need of antiretroviral treatment had accessed it by the end of 2006, Malawi is well on its way to meeting its universal access treatment target of 50%. A clear priority in Malawi has been to promote equity in access to its free treatment first-come first-served programme that has been running since 2004. Significant barriers to achieving equity in access are the cost of transport and food as well as the opportunity costs of missing work, particularly when tuberculosis and antiretroviral treatment programmes are parallel, vertical programmes requiring separate clinic visits. Monitoring the age, sex, and socioeconomic status of people undergoing HIV testing and accessing HIV treatment services in all countries can help identify inequities that are unnecessary, avoidable, and unfair so that they can be rectified.

Cornell M, Myer L, Kaplan R, Bekker LG, Wood R. The impact of gender and income on survival and retention in a South African antiretroviral therapy programme. Trop Med Int Health. 2009 Apr 27. [Epub ahead of print]

Despite the rapid expansion of antiretroviral therapy services in Africa, there are few data on whether outcomes differ for women and men and what factors may drive such variation. Cornell and colleagues investigated the association of gender and income with survival and retention in a South African antiretroviral therapy programme. A total of 2196 treatment-naïve adults were followed for 1 year on antiretroviral therapy. Proportional hazards regression was used to explore associations between baseline characteristics and survival and loss-to-follow-up. Patients were predominantly female (67%). Men presented at an older age and with more advanced HIV disease, and during early antiretroviral therapy the crude death rate was higher among men than women (22.8 vs 12.5/100 person-years; P = 0.002). However in multivariate analysis, gender was not significantly associated with survival after adjusting for baseline clinical and immunovirological status (HR = 1.46, 95% CI = 0.96-2.22; P = 0.076). In late antiretroviral therapy (4-12 months), there was no gender difference in mortality rates (3.5 vs 3.8/100 person-years; P = 0.817). In multivariate analysis, survival was strongly associated with age (HR = 1.05, 95% CI = 1.02-1.09; P < 0.001), CD4 count >150 vs <50 cells/mul (HR = 0.35, 95% CI = 0.14-0.87; P = 0.023) and any monthly income vs none (HR = 0.47, 95% CI = 0.25-0.88; P = 0.018). Having some monthly income was protective against loss-to-follow-up at 1 year on antiretroviral therapy (adjusted HR = 0.56, 95% CI = 0.39-0.82; P = 0.002). Men’s high early mortality on antiretroviral therapy appears due largely to their presentation with more advanced HIV disease. Efforts are needed to enrol men into care earlier in HIV disease and to reduce socio-economic inequalities in antiretroviral therapy programme outcomes.

Editors’ note: This study provides additional evidence to support the need for strategies to increase men’s exposure to health services and decrease their disadvantages in access to HIV testing and treatment in resource-constrained settings. Some of the barriers are psychosocial while others are structural. This study also found that people with no monthly income experience poorer treatment outcomes: Compared to women with no monthly income, men with no monthly income had nearly twice the crude hazard of death. Socioeconomic interventions, such as the proposed basic income grant in South Africa, may improve patient retention and survival in antiretroviral treatment programmes.

Moran M, Guzman J, Ropars AL, McDonald A, Jameson N, Omune B, Ryan S, Wu L. Neglected disease research and development: how much are we really spending? PLoS Med. 2009;6(2):e30.

The need for new pharmaceutical tools to prevent and treat neglected diseases is widely accepted. However, funders wishing to invest in this vitally important area currently face an information gap. In order to address these information deficits, the Bill & Melinda Gates Foundation commissioned the George Institute for International Health to conduct five sequential annual surveys of global investment into research and development (R&D) of new pharmaceutical products to prevent, manage, or cure diseases of the developing world. This article summarises key data from the first G-FINDER report. G-FINDER was designed to include all neglected diseases and products of significance to developing countries, seeking to capture 2007 data from more than 500 funders and countries. Just over US$2.5 billion was invested into R&D of new neglected disease products in 2007. Funding was highly concentrated, with AIDS, TB, and malaria receiving nearly 80% of the total. Overall, product R&D investment was heavily focused on drugs and vaccines. Investment in new diagnostics was patchy, while platform technologies applicable to many diseases, for instance vaccine adjuvants, diagnostic platforms, and delivery technologies, received less than 0.4% of total R&D investment. Neglected disease funding remains primarily the realm of public and philanthropic donors, who collectively invested US$2.3 billion or 90% of the total funding in 2007. Several major OECD ( Organisation for Economic Co-operation and Development) governments were missing in action from the top 10, top 20, or even the top 50 funders of R&D for neglected diseases . It is also remarkable that investment by some private firms is now rivalling or exceeding spending by many public organizations. While the authors commend these companies and philanthropists, their efforts are meant to support, not replace, those of wealthy governments around the world. A broadening of funding efforts so that all who are able to contribute do so, and all diseases receive the attention they deserve, would lead to a dramatic positive impact on the health of developing country patients afflicted with these diseases.

Editors’ note: Neglected diseases were defined in this survey research as diseases that disproportionately affect people in developing countries for which there is a need for new products and for which there is market failure, i.e. there is no commercial market to attract research and development by private industry. This survey, which included a wide range of funders and countries, found little correlation between research funding and burden of disease, as measure by disability-adjusted life years (DALYs). This suggests that beyond scientific and epidemiological considerations, investment decisions may be influenced by donor perceptions and preferences, the presence of policy frameworks and funding mechanisms that prioritise specific diseases, the possibility of product development partnerships, and the influence of civil society advocacy. However, the overall pie is too small for the task and it is clearly time for those who can contribute to step forward now.

Menzies N, Abang B, Wanyenze R, Nuwaha F, Mugisha B, Coutinho A, Bunnell R, Mermin J, Blandford JM. The costs and effectiveness of four HIV counselling and testing strategies in Uganda. AIDS. 2009;23(3):395-401.

HIV counselling and testing is a key intervention for HIV control, and new strategies have been developed for expanding coverage in developing countries. Menzies and colleagues compared costs and outcomes of four HIV counselling and testing strategies in Uganda. A retrospective cohort of 84 323 individuals received HIV counselling and testing at one of four Ugandan HIV counselling and testing programmes between June 2003 and September 2005. Strategies assessed were stand-alone; hospital-based; household-member; and door-to-door. The authors collected data on client volume, demographics, prior testing and HIV diagnosis from project monitoring systems, and cost data from project accounts and personnel interviews. Strategies were compared in terms of costs and effectiveness at reaching key population groups. Household-member and door-to-door HIV counselling and testing strategies reached the largest proportion of previously untested individuals (>90% of all clients). Hospital-based HIV counselling and testing diagnosed the greatest proportion of HIV-infected individuals (27% prevalence), followed by stand-alone HIV counselling and testing (19%). Household-member HIV counselling and testing identified the highest percentage of discordant couples; however, this was a small fraction of total clients (<4%). Costs per client (2007 USD) were $19.26 for stand-alone, $11.68 for hospital-based, $13.85 for household-member, and $8.29 for door-to-door- HIV counselling and testing. All testing strategies had relatively low per client costs. Hospital-based HIV counselling and testing most readily identified HIV-infected individuals eligible for treatment, whereas home-based strategies more efficiently reached populations with low rates of prior testing and HIV-infected people with higher CD4 cell counts. Multiple HIV counselling and testing strategies with different costs and efficiencies can be used to meet the UNAIDS/WHO call for universal HIV counselling and testing access by 2010.

Editors’ note: This useful cost-effectiveness study of four different HIV counselling and testing strategies that a national HIV programme might consider demonstrates the value of each in a generalized epidemic. More than 30 per cent (range 30.7-48.1 per cent) of all people found HIV-positive had advanced immunosuppression (CD4+ count <200 cells/μl) regardless of testing strategy. Door-to-door strategies reached previously untested people cheaply in this country where in 2007 less than a quarter of people had ever been tested. These data indicate that a variety of testing strategies, providing choices for individuals, couples, and communities, can work in complementary fashion to accomplish the goals of increasing knowledge of serostatus and facilitating earlier treatment initiation.

Paltiel AD, Freedberg KA, Scott CA, Schackman BR, Losina E, Wang B, Seage Iii GR, Sloan CE, Sax PE, Walensky RP. HIV Preexposure Prophylaxis in the United States: Impact on Lifetime Infection Risk, Clinical Outcomes, and Cost-Effectiveness. Clin Infect Dis. 2009;48(6):806-815.

The combination of tenofovir and emtricitabine shows promise as HIV preexposure prophylaxis (PrEP). Paltiel and colleagues sought to forecast clinical, epidemiologic, and economic outcomes of PrEP, taking into account uncertainties regarding efficacy, the risks of developing drug resistance and toxicity, behavioural disinhibition, and drug costs. They adapted a computer simulation of HIV acquisition, detection, and care to model PrEP among men who have sex with men and are at high risk of HIV infection (i.e., 1.6% mean annual incidence of HIV infection) in the United States. Base-case assumptions included 50% PrEP efficacy and monthly tenofovir-emtricitabine costs of $753. They used sensitivity analyses to examine the stability of results and to identify critical input parameters. In a cohort with a mean age of 34 years, PrEP reduced lifetime HIV infection risk from 44% to 25% and increased mean life expectancy from 39.9 to 40.7 years (21.7 to 22.2 discounted quality-adjusted life-years). Discounted mean lifetime treatment costs increased from $81,100 to $232,700 per person, indicating an incremental cost-effectiveness ratio of $298,000 per quality-adjusted life-year gained. Markedly larger reductions in lifetime infection risk (from 44% to 6%) were observed with the assumption of greater (90%) PrEP efficacy. More-favourable incremental cost-effectiveness ratios were obtained by targeting younger populations with a higher incidence of infection and by improvements in the efficacy and cost of PrEP. PrEP could substantially reduce the incidence of HIV transmission in populations at high risk of HIV infection in the United States. Although it is unlikely to confer sufficient benefits to justify the current costs of tenofovir-emtricitabine, price reductions and/or increases in efficacy could make PrEP a cost-effective option in younger populations or populations at higher risk of infection. Given recent disappointments in HIV infection prevention and vaccine development, additional study of PrEP-based HIV prevention is warranted.

Editors’ note: To date, evidence from animal studies indicates promise for pre-exposure prophylaxis (PrEP) but none of the eight oral and/or topical PrEP trials planned or currently underway in a variety of populations have reported results. Based on current treatment costs for tenofovir-emtricitabine and conservative estimates of efficacy, PrEP is an unattractive option from a US-based cost-effectiveness perspective but reduced costs and increased efficacy would improve the incremental cost-effectiveness ratio (dollars per quality adjusted life years [QALYs] gained). Now let’s get some real data to inform such modelling!

Sridhar D, Batniji R. Misfinancing global health: a case for transparency in disbursements and decision making. Lancet 2008; 27;372(9644):1185-91.

To address the gap between health investments and financial flows worldwide, Sridhar and Batniji identified the patterns in allocation of funds by the four largest donors—ie, the World Bank, Bill & Melinda Gates Foundation, the US Government, and the Global Fund to Fight HIV/AIDS, Tuberculosis and Malaria—in 2005. They created a disbursement database with information gathered from the annual reports and budgets. Funding per death varied widely according to type of disease—eg, US$1029.10 for AIDS to $3.21 for non-communicable diseases. The World Bank, US Government, and Global Fund provided more than 98% of their funds to service delivery, whereas Bill & Melinda Gates Foundation gave most of its funds to research. Bill & Melinda Gates Foundation grants in 2005 were given largely to private research organisations, universities, and civil societies in rich countries, whereas the US Government and Global Fund primarily disbursed grants to sub-Saharan Africa. Publicly available data for global health disbursements is incomplete and not standardised. Continued attention is needed to develop country ownership, particularly in planning and priority setting.

Edtiors’ note: The four major global health donors analysed here account for only a third of all donor funding for global health. Nonetheless, they are big players and this study of their comparative mandates and disbursements is revealing. Data on their disbursements are of variable quality, disease burden estimates are imprecise, and their decision-making processes were not assessed. With global health governance being a patchwork of donors, UN agencies, governments, civil society organisations, and the private sector, much remains to be done to implement the Paris Declaration which envisages decision-making based on the articulated needs of developing countries.

Bendavid E, Young SD, Katzenstein DA, Bayoumi AM, Sanders GD, Owens DK. Cost-effectiveness of HIV monitoring strategies in resource-limited settings: a southern African analysis. Arch Intern Med 2008; 22;168(17):1910-8.

Although the number of infected persons receiving highly active antiretroviral therapy in low- and middle-income countries has increased dramatically, optimal disease management is not well defined. Bendavid and colleagues developed a model to compare the costs and benefits of 3 types of human immunodeficiency virus monitoring strategies: symptom-based strategies, CD4-based strategies, and CD4 counts plus viral load strategies for starting, switching, and stopping antiretroviral therapy. They used clinical and cost data from southern Africa and performed a cost-effectiveness analysis. All assumptions were tested in sensitivity analyses. Compared with the symptom-based approaches, monitoring CD4 counts every 6 months and starting treatment at a threshold of 200/muL was associated with a gain in life expectancy of 6.5 months (61.9 months vs. 68.4 months) and a discounted lifetime cost savings of US $464 per person (US $4069 vs. US $3605, discounted 2007 dollars). The CD4-based strategies in which treatment was started at the higher threshold of 350/microL provided an additional gain in life expectancy of 5.3 months at a cost-effectiveness of US $107 per life-year gained compared with a threshold of 200/microL. Monitoring viral load with CD4 was more expensive than monitoring CD4 counts alone, added 2.0 months of life, and had an incremental cost-effectiveness ratio of US $5414 per life-year gained relative to monitoring of CD4 counts. In sensitivity analyses, the cost savings from CD4 count monitoring compared with the symptom-based approaches was sensitive to cost of inpatient care, and the cost-effectiveness of viral load monitoring was influenced by the per test costs and rates of virologic failure. Use of CD4 monitoring and early initiation of antiretroviral therapy in southern Africa provides large health benefits relative to symptom-based approaches for antiretroviral therapy management. In southern African countries with relatively high costs of hospitalization, CD4 monitoring would likely reduce total health care expenditures. The cost-effectiveness of viral load monitoring depends on test prices and rates of virologic failure.

Editors’ note: Using the often cited ‘twice the per capita gross domestic product’ as an acceptable cost-effectiveness ratio for developing countries, monitoring CD4 counts is cost-effective in all parts of southern Africa. Using CD4 count monitoring to initiate antiretroviral treatment at 350 cells/µl, before onset of serious opportunistic diseases and severe immune compromise, can be facilitated by recent advances in CD4 enumeration technology with lower per test costs. Smaller machines have been now designed that require less infrastructure, maintenance, and technical expertise.

Moon S, Van Leemput L, Durier N, Jambert E, Dahmane A, Jie Y, Wu G, Philips M, Hu Y, Saranchuk P. Out-of-pocket costs of AIDS care in China: are free antiretroviral drugs enough? AIDS Care. 2008;20(8):984-94.

Financial access to HIV care and treatment can be difficult for many people in China, where the government provides free antiretroviral drugs but does not cover the cost of other medically necessary components, such as lab tests and drugs for opportunistic infections. This article estimates out-of-pocket costs for treatment and care that a person living with HIV in China might face over the course of one year. Data comes from two treatment projects run by Médecins Sans Frontières in Nanning, Guangxi Province and Xiangfan, Hubei Province. Based on the national treatment guidelines, Moon and colleagues estimated costs for seven different patient profiles ranging from WHO Clinical Stages I through IV. They found that patients face significant financial barriers to even qualify for the free antiretroviral treatment program. For those who do, HIV care and treatment can be a catastrophic health expenditure, with cumulative patient contributions ranging from approximately US$200-3939/year in Nanning and US$13-1179/year in Xiangfan, depending on the patient’s clinical stage of HIV infection. In Nanning, these expenses translate as up to 340% of an urban resident’s annual income or 1200% for rural residents; in Xiangfan, expenses rise to 116% of annual income for city dwellers and 295% in rural areas. While providing antiretroviral drugs free of charge is an important step, the costs of other components of care constitute important financial barriers that may exclude patients from accessing appropriate care. Such barriers can also lead to undesirable outcomes in the future, such as impoverishment of AIDS-affected households, higher antiretroviral drug-resistance rates and greater need for complex, expensive second-line antiretroviral drugs.

Editors’ note: Using data demonstrating that, for many people on HIV treatment in China, out-of-pocket expenditures reach ‘catastrophic’ health expenditure levels, the authors urge policy makers to consider both patient health and long-term treatment programme viability in designing strategies to prevent widespread resistance. Out-of-pocket expenditures create serious impediments for people who need antiretroviral therapy to access treatment, attend clinic regularly, and achieve high adherence levels. There are cogent economic arguments in favour of a free minimum package of HIV care that goes beyond antiretroviral drugs to include HIV tests, consultations, laboratory testing, hospitalisation, prophylaxis, and treatment of common opportunistic infections.

Alkenbrack Batteh SE, Forsythe S, Martin G, Chettra T. Confirming the impact of HIV/AIDS epidemics on household vulnerability in Asia: the case of Cambodia. AIDS. 2008;22 Suppl 1:S103-11.

This study explores the effects of HIV on household economics and the social wellbeing of children in HIV-affected families in Cambodia. A purposive sample of parents living with HIV and their children was selected from networks of people living with HIV. ‘Nearest-neighbour’ households served as the comparison group. Interviews were conducted with the parent and at least one child or adolescent in each household between October 2003 and January 2004. The urban/rural sample included 1000 households, 1000 adults, and 1443 children aged 6-17 years, inclusive, and was drawn from Phnom Penh, Battambang and Takeo provinces. Despite similar overall expenditures, HIV-affected households incurred proportionately larger expenditures on medical care and funerals. Income among case households was lower than comparison households. HIV-affected households were more likely to sell off assets, borrow from family members, take out loans, and ration medical care and food for children. Children in HIV-affected households reported eating fewer meals in a day, increased frequency of hunger, and increased household and employment responsibilities compared with comparison children. School enrollment rates were similar between pairs of households. The results add to growing evidence that HIV contributes to increased vulnerability to poverty and increased burdens on families and children. This study corroborates findings from previous studies in Asia, while providing country-specific information to stakeholders in Cambodia. At this stage in the epidemic, policy makers should focus on implementing and evaluating mitigation interventions.

Editors’ note: Using a ‘nearest neighbour’ comparison group to try to disentangle risk from impact (HIV and poverty are known to influence each other with HIV exacerbating poverty and poverty increasing HIV exposure risk), this large study confirms the dissaving associated with HIV-related illnesses. Economic survival strategies come at the expense of longer-term investments in the household affecting future generations. Children in HIV-affected households are significantly disadvantaged compared to their neighbouring peers despite the food assistance provided to 81% of the case households. Implementation and evaluation of comprehensive mitigation strategies are urgently needed to inform policymaking and minimise the long-term impacts of HIV on low-income countries such as Cambodia.

H W Reynolds, B Janowitz, R Wilcher, W Cates. Contraception to prevent HIV-positive births: current contribution and potential cost savings in PEPFAR countries. Sex. Transm. Inf. 2008;84;ii49-ii53

Reynolds et al aimed to estimate the number of HIV-positive births currently prevented by contraceptive use in the President’s Emergency Plan for AIDS Relief (PEPFAR) focus countries and to estimate the first year cost savings to each country if unintended and unwanted HIV-positive births were prevented via contraceptive use rather than providing antiretroviral prophylaxis for HIV-positive pregnant women (prevention of mother-to-child transmission services). Data from publicly available sources yielded estimates of (1) contraceptive and HIV prevalence; (2) the number of women of reproductive age; (3) the number of annual births to HIV-infected women; (4) the rates of pregnancy and vertical HIV transmission; (5) the proportions of unintended and unwanted births; and (6) the cost per HIV-positive birth averted by family planning and prevention of mother-to-child transmission services. The number of HIV-positive births currently averted by contraceptive use and the number of unwanted and unintended HIV-positive births are the product of these estimates. Cost savings are the difference in the costs of family planning and prevention of mother-to-child transmission services. The study found that the annual number of unintended HIV-positive births currently averted by contraceptive use ranges from 178 in Guyana to over 120,000 in South Africa. The minimum annual cost savings to prevent just the unwanted HIV-positive births ranges from $26,000 in Vietnam to over $2.2 million in South Africa. The authors concluded that contraception is already having an important effect on reducing the number of infant HIV infections. This contribution could be strengthened by additional efforts to provide contraception to HIV-infected women who do not wish to become pregnant. Moreover, the effect of contraception can be achieved at a cost savings compared with prevention of mother-to-child transmission services.

Editors’ note: Despite low contraceptive prevalence rates, contraception is already preventing many unintended HIV-positive births. Contraception helps women with HIV delay pregnancy until they are emotionally and physically ready and can access appropriate antenatal and safe delivery care, as well as antiretroviral regimens. Important cost savings could be incurred if more women living with HIV were able to prevent mistimed or unwanted pregnancy in the first place rather than interrupting mother-to-child transmission through antiretroviral prophylaxis. Cost-effective compared with other approaches to prevent mother-to-child transmission, family planning really is the best-kept secret of HIV prevention.

Auvert B, Marseille E, Korenro§mp EL, Lloyd-Smith J, Sitta R, Taljaard D, Pretorius C, Williams B, Kahn JG. Estimating the resources needed and savings anticipated from roll-out of adult male circumcision in Sub-Saharan Africa. PLoS ONE. 2008;3(8):e2679.

Trials in Africa indicate that medical adult male circumcision reduces the risk of HIV by 60%. Medical adult male circumcision may avert 2 to 8 million HIV infections over 20 years in sub-Saharan Africa and cost less than treating those who would have been infected. This paper estimates the financial and human resources required to roll out medical adult male circumcision and the net savings due to reduced infections. Auvert and colleagues developed a model which included costing, demography, and HIV epidemiology and used it to investigate 14 countries in sub-Saharan Africa where the prevalence of male circumcision was lower than 80% and HIV prevalence among adults was higher than 5%, in addition to Uganda and the Nyanza province in Kenya. The authors assumed that the roll-out would take 5 years and lead to a male circumcision prevalence among adult males of 85%. They also assumed that surgery would be done as it was in the trials. They calculated public program cost, number of full-time circumcisers and net costs or savings when adjusting for averted HIV treatments. Costs were in USD, discounted to 2007. 95% percentile intervals (95% PI) were estimated by Monte Carlo simulations. In the first 5 years the number of circumcisers needed was 2 282 (95% PI: 2 018 to 2 959), or 0.24 (95% PI: 0.21 to 0.31) per 10,000 adults. In years 6-10, the number of circumcisers needed fell to 513 (95% PI: 452 to 664). The estimated 5-year cost of rolling out medical adult male circumcision in the public sector was $919 million (95% PI: 726 to 1 245). The cumulative net cost over the first 10 years was $672 million (95% PI: 437 to 1,021) and over 20 years there were net savings of $2.3 billion (95% PI: 1.4 to 3.4). The authors conclude that a rapid roll-out of medical adult male circumcision in sub-Saharan Africa requires substantial funding and a high number of circumcisers for the first five years. These investments are justified by medical adult male circumcision’s substantial health benefits and the savings accrued by averting future HIV infections. Lower ongoing costs and continued care savings suggest long-term sustainability.

Editors’ note: This modelling optimistically assumes that the proportion of men circumcised in these 15 countries plus Nyanza Province, Kenya will rise from a range of 0 to 70% (in 2007 the number of uncircumcised males aged 15 to 49 was 30.5 million) to 85% in five years. This would require very high demand for services as well as unprecedented capacity for well-trained, adequately equipped, health care personnel to meet that demand safely. Although relevant costs were contained in the modelling, the cost of HIV testing and counselling was not, with the authors stating that it ‘may not be required by many male circumcision programmes’. WHO/UNAIDS advise health professionals to recommend voluntary HIV testing to all individuals seeking male circumcision services. Asymptomatic HIV-positive men and healthy men of unknown serostatus who do not wish to be tested should not be refused circumcision unless there are medical contraindications. However, consistent with provider-initiated testing policies, men requesting circumcision should be given the opportunity to learn their HIV status.

Souteyrand YP, Collard V, Moatti JP, Grubb I, Guerma T. Free care at the point of service delivery: a key component for reaching universal access to HIV/AIDS treatment in developing countries. AIDS. 2008 Jul;22 Suppl 1:S161-8.

User fees are a common feature of health system financing in low and middle-income countries. In the context of universal access to HIV treatment and care, the advantages of user fees for funding at country and local level should be balanced with their clinical and public health impact. Souteyrand et al reviewed the literature on user fees and the impact of user fees on HIV service delivery. Empirical evidence gathered since the 1980s shows that sustainability, efficiency and equity challenges faced by health systems have persisted with and have often been exacerbated by the introduction of user fees. The evidence on HIV suggests that free care at the point of service fosters uptake and helps to extend access for the poorest users. User fees are currently the main barrier to adherence to antiretroviral therapy. Their abolition is associated with better virological results and increased survival. Such abolition should be carried out in parallel with the implementation of financing mechanisms, such as prepayment and risk pooling, which are able to gather funds from the sectors of the population who are able to pay for healthcare and to promote equity towards the poorest. WHO has included free access to HIV treatment at the point of service delivery as a component of its public health approach for reaching universal access. Implementation of free HIV care should, however, be linked to efforts to strengthen healthcare systems, ensure long-term sustainability of funding and monitor equity of access to care.

Editors’ note: Financial barriers cannot be allowed to provoke non-adherence and compromise first-line treatment regimens. In March 2005, countries were advised to adopt a policy of free access to HIV treatment at the point of service delivery, following a WHO/UNAIDS/World Bank consultation. Abolition of user fees and introduction or strengthening of more equitable funding mechanisms can create positive spillover that increases access and strengthens health care infrastructure as a whole.

The number of people in the world living with HIV is increasing as HIV-related mortality has declined but the annual number of people newly infected with HIV has not. The international response to contain the HIV pandemic, meanwhile, has grown. Since 2006, an international commitment to scale up prevention, treatment, care and support services in middle and lower-income countries by 2010 has been part of the Universal Access programme, which itself plays an important part in achieving the Millennium Development Goals by 2015. Apart from providing technical support, donor countries and agencies have substantially increased their funding to enable countries to scale up HIV services. Many countries have been developing their HIV monitoring and evaluation systems to generate the strategic information required to track their response and ensure the best use of the new funds. Financial information is an important aspect of the strategic information required for scaling up existing services as well as assessing the effect of new ones. It involves two components: tracking the money available and spent on HIV at all levels, through budget tracking, national health accounts and national AIDS spending assessments, and estimating the cost and efficiency of HIV services. The cost of service provision should be monitored over time, whereas evaluations of the cost-effectiveness of services are required periodically; both should be part of any country’s HIV monitoring and evaluation system. This paper provides country examples of the complementary relationship between monitoring the cost of HIV services and evaluating their cost-effectiveness. It also summarizes global initiatives that enable countries to develop their own HIV monitoring and evaluation systems and to generate relevant, robust and up-to-date strategic information.

Editors’ note: If you have been lost in the jargon, this paper sorts out the differences between effectiveness (outcome or impact of programmes or services), efficiency (resources require to achieve a certain outcome or impact), equity (who benefits from programmes or services), and acceptability (both to users and providers of services and in terms of improvements in the quality of life that programmes achieve). These criteria are supported by other pieces of strategic information that underpin a plan of action for programmes or services, such as direct and indirect costs and HIV incidence/prevalence. Topping this off with a robust monitoring and evaluation system, similar to those that many countries are now developing, can enhance country responses.

Morin SF, Morfit S, Maiorana A, Aramrattana A, Goicochea P, Mutsambi JM, Robbins JL, Richards TA. Building community partnerships: case studies of Community Advisory Boards at research sites in Peru, Zimbabwe, and Thailand. Clin Trials. 2008;5(2):147-56.

Differences in resources, knowledge, and infrastructure between countries initiating and countries hosting HIV prevention research trials frequently yield ethical dilemmas. Community Advisory Boards have emerged as one strategy for establishing partnerships between researchers and host communities to promote community consultation in socially sensitive research. Morin and co-authors undertook to understand the evolution of Community Advisory Boards and community partnerships at international research sites conducting HIV prevention trials. Three research sites of the HIV Prevention Trials Network (HPTN) were selected to include geographical representation and diverse populations at risk for HIV exposure – Lima, Peru; Chitungwiza, Zimbabwe; and Chiang Mai, Thailand. Data collection included review of secondary data, including academic publications and site-specific progress reports; observations at the research sites; face-to-face interviews with Community Advisory Boards members, research staff, and other key informants; and focus groups with study participants. Rapid assessment techniques were used for data analysis. The authors found that two of the three Community Advisory Boards developed new strategies for community representation in response to new studies. All three Community Advisory Boards expanded their original function and became advocates for broader community interests beyond HIV prevention. The participation and input of community representatives, in response to critical incidents that occurred at the sites over the past five years, helped to solidify partnerships between researchers and communities. In terms of limitations the authors point out that Rapid Assessment is an exploratory methodology designed to provide an understanding of a situation based on the integration of multiple data sources, collected within a short period of time, without a formal examination of transcribed and coded data. Case studies, as a method, are meant to draw out what can be learned from a single case but are not, in the scientific sense, generalizable. They conclude that in developing countries, Community Advisory Boards can be dynamic entities that enhance the HIV research process, assist in responding to issues involving research ethics, and prepare communities for HIV research.

Editors´note: This assessment of changes in community advisory board conduct and roles over a five year period found that at each site a conflict or challenge arose in which the views and assistance of community advisory board members became not only valuable to the research team but also important for the future success of the research. These conflicts or challenges generated substantial interactions of mutual benefit as issues were debated which led to a more genuine partnership. Community advisory boards clearly can be dynamic entities striving to better represent and advocate for the communities.

Djomand G, Metch B, Zorrilla CD, Donastorg Y, Casapia M, Villafana T, Pape J, Figueroa P, Hansen M, Buchbinder S, Beyrer C; for the 903 Protocol Team. The HVTN Protocol 903 Vaccine Preparedness Study: Lessons Learned in Preparation for HIV Vaccine Efficacy Trials. J Acquir Immune Defic Syndr. 2008;48(1):82-9 2008

Successful recruitment and retention of HIV-uninfected at-risk participants are essential for HIV vaccine efficacy trials. A multicountry vaccine preparedness study was started in 2003 to assess enrolment and retention of HIV-negative high-risk participants, and to assess their willingness to participate in future vaccine efficacy trials. HIV-negative high-risk adults were recruited in the Caribbean, in Southern Africa, and in Latin America, and were followed for 1 year. Participants included men who have sex with men, heterosexual men and women, and female sex workers. History of sexually transmitted infections and sexual risk behaviours were recorded with HIV testing at 0, 6, and 12 months, and willingness to participate in future vaccine trials was recorded at 0 and 12 months. Recruitment, retention, and willingness to participate in future trials were excellent at 3 of the 6 sites, with consistent declines in risk behaviours across cohorts over time. Although not powered to measure seroincidence, HIV seroincidence rates per 100 person-years (95% confidence interval [CI]) were as follows: 2.3 (95% CI: 0.3 to 8.2) in Botswana, 0.5 (95% CI: 0 to 2.9) in the Dominican Republic, and 3.1 (95% CI: 1.1 to 6.8 ) in Peru. The HIV Vaccine Trials Network 903 study helped to develop clinical trial site capacity, with a focus on recruitment and retention of high-risk women in the Americas, and improved network and site expertise about large-scale HIV vaccine efficacy trials.

Editors´note: Finding populations with sufficient risk for HIV infection to support the seroincidence demands of trials is a start but they must also have high rates of retention for there to be adequate power to confirm or refute the study’s hypothesis. Even participating in a study to assess enrolment, retention, and HIV incidence can lead to declines in risk behaviour and HIV incidence, above those already happening in the overall general population. Such a positive effect of being studied is sometimes called the Hawthorne Effect.

Hughes S, L Cuffe R, Lieftucht A, Garrett Nichols W. Informing the selection of futility stopping thresholds: case study from a late-phase clinical trial. Pharm Stat. 2008 Mar 27 [Epub ahead of print]

In an environment where (i) potential risks to subjects participating in clinical studies need to be managed carefully, (ii) trial costs are increasing, and (iii) there are limited research resources available, it is necessary to prioritize research projects and sometimes re-prioritize if early indications suggest that a trial has low probability of success. Futility designs allow this reprioritization to take place. This paper reviews a number of possible futility methods available and presents a case study from a late-phase study of an HIV therapeutic, which utilized conditional power-based stopping thresholds. The two most challenging aspects of incorporating a futility interim analysis into a trial design are the selection of optimal stopping thresholds and the timing of the analysis, both of which require the balancing of various risks. The paper outlines a number of graphical aids that proved useful in explaining the statistical risks involved to the study team. Further, the paper outlines a decision analysis undertaken which combined expectations of drug performance with conditional power calculations in order to produce probabilities of different interim and final outcomes, and which ultimately led to the selection of the final stopping thresholds.

Editors´note: Early indications that a trial has low probability of success – with success defined as confirming or refuting the trial hypothesis – can lead to the stopping of a trial for futility. Although this saves resources, stopping a trial prior to its conclusion because its key endpoints will not be met makes it impossible to determine whether results for secondary endpoints would have generated useful hypotheses for future investigation. It is important to decide up front what the stopping rules will be with respect to all endpoints and understand the consequences and anticipate them.