HIV/AIDS resource allocation decisions are influenced by political, social, ethical and other factors that are difficult to quantify. Consequently, quantitative models of HIV/AIDS resource allocation have had limited impact on actual spending decisions. We propose a decision-support System for HIV/AIDS Resource Allocation (S4HARA) that takes into consideration both principles of efficient resource allocation and the role of non-quantifiable influences on the decision-making process for resource allocation.S4HARA is a four-step spreadsheet-based model. The first step serves to identify the factors currently influencing HIV/AIDS allocation decisions. The second step consists of prioritizing HIV/AIDS interventions. The third step involves allocating the budget to the HIV/AIDS interventions using a rational approach. Decision-makers can select from several rational models of resource allocation depending on availability of data and level of complexity. The last step combines the results of the first and third steps to highlight the influencing factors that act as barriers or facilitators to the results suggested by the rational resource allocation approach. Actionable recommendations are then made to improve the allocation. We illustrate S4HARA in the context of a primary healthcare clinic in South Africa.The clinic offers six types of HIV/AIDS interventions and spends US$750,000 annually on these programs. Current allocation decisions are influenced by donors, NGOs and the government as well as by ethical and religious factors. Without additional funding, an optimal allocation of the total budget suggests that the portion allotted to condom distribution be increased from 1% to 15% and the portion allotted to prevention and treatment of opportunistic infections be increased from 43% to 71%, while allocation to other interventions should decrease.Condom uptake at the clinic should be increased by changing the condom distribution policy from a pull system to a push system. NGOs and donors promoting antiretroviral programs at the clinic should be sensitized to the results of the model and urged to invest in wellness programs aimed at the prevention and treatment of opportunistic infections. S4HARA differentiates itself from other decision support tools by providing rational HIV/AIDS resource allocation capabilities as well as consideration of the realities facing authorities in their decision-making process. Available funding for HIV and AIDS in low- and middle-income countries is estimated at US$27 billion in total for the years 2005 to 2007. However, that amount represents only 60% of the resource requirements estimated at US$45 billion in the same period . Though Resource allocation can be defined as the process of distributing funds or resources among intervention programs that are competing for the same budget. There are several types of rational models that can be used to support the decision-making process for HIV/AIDS resource allocation. Equity is perceived as an important value representing fairness and distributive justice -4. SimplMore comprehensive approaches to resource allocation include simulation models used to project the epidemic over time and compare the outcome of alternative allocation scenarios ,9. A numDespite the increased acceptance of such rational models and their potential to produce very good results, their impact on health care resource allocation in practice has been rather limited -16. In aSeveral reasons have been discussed regarding the practical usability of rational resource allocation models. First, models are often complex and there is limited data or capacity to use them in low-income settings. In developing countries, barriers to the use of quantitative decision models in health care include a shortage of trained analysts and other personnel with the capacity to manipulate models, as well as a lack of awareness of models and their contributions ,19. AndeSecond, resource allocation decisions can not be made in a socio-political vacuum . ResourcThird, rational models of resource allocation are useful to optimize the expected outcome for a single decision-making authority . HoweverIn a study of the use of operations research models in developing countries, Ravn and Vidal suggest that education in industrialized countries produces researchers who believe that to be scientific one ought to be politically neutral; but that both scientific analysis and political engagement are necessary to implement appropriate models in developing countries . DespiteIn view of these limitations to the use and usability of rational resource allocation models, we propose a decision-support System for HIV/AIDS Resource Allocation (S4HARA) that takes into consideration both principles of efficient resource allocation and the role of non-quantifiable influences on the decision-making process for HIV/AIDS resource allocation. S4HARA enables decision-makers to select from several rational models of resource allocation depending on availability of data and level of complexity. We validate S4HARA by demonstrating its application in the context of a health care clinic in South Africa.The remainder of this paper is organized as follows: we begin with a description of S4HARA; we then apply the system to a primary health care clinic in South Africa and describe the results. Finally, we conclude with some recommendations, known limitations and suggestions for future work.S4HARA is a four-step spreadsheet-based decision-support system for allocating funds to HIV/AIDS programs at a local level. S4HARA is aimed at local government agencies, non-governmental organizations or public health institutions currently offering HIV and AIDS programs in a low-income community. Though the primary user of S4HARA is the person in charge of budget planning within a given organization, consultation with several key contacts is required to gather input for the construction of a S4HARA model.The flow diagram in Figure S4HARA is designed to run on Microsoft Excel. Excel was selected as the platform for running S4HARA because of its widespread availability.In this step the user is required to collect data including population size, HIV prevalence, number of AIDS cases, the resource allocation planning horizon and the total budget. For each HIV/AIDS program offered by the organization, the user will compile the available data related to program utilization rates, such as the number of visits, material expenses and, if possible, program costs and outcome data. The WHO-CHOICE project is a useful source for identifying regional estimates of intervention costs and outcomes . If costInfluence diagrams can be useful for illustrating problems that are difficult to quantify. In this step, an influence diagram is used to create a graphical representation of the factors that bear a positive or a negative influence on the implementation of the HIV/AIDS programs offered. The output of this step will be used as input to the final step.The influence diagram is composed of two types of nodes: program nodes representing the HIV/AIDS programs offered; and factor nodes representing the influencing factors. Program nodes are predefined based on the results of the situation analysis (Step 1).The user is provided with a default set of nodes based on previous research. In previous research, we identified several bodies or groups that influence the decision-making process for HIV/AIDS resource allocation in low-income settings, including: donors, advocacy groups, NGOs, government agencies, communities and the media . We alsoNodes can be connected by two types of arcs; positive arcs are green and represent a positive influence between a factor node and a program node, and negative arcs are red and represent a negative influence between a factor node and a program node.By default the influence diagram contains both program nodes and factor nodes but no arcs. For every combination of factor node and program node, the user must assess whether the factor bears an influence on the allocation of resources to the program and if so, whether it is a positive or a negative influence. Accordingly, the user will add positive and negatives arcs to the influence diagram. For example, the user may ask: "Does religion have an influence on the implementation of a condom distribution program? And, if so, is it a positive influence which encourages condom distribution or a negative influence which impedes condom distribution?" To improve the accuracy of answers, the user should consult with as many qualified respondents as possible. The thickness of the arcs should be used to determine the relative importance of the influence.In this step, the user selects and applies one of three HIV/AIDS resource allocation methods: priority setting, equity or optimization.We define priority setting as an ordinal ranking of the programs according to the situation analysis. This approach does not require cost or outcome data and is recommended if information on current levels of funding or utilization for each program is limited.In S4HARA, priority setting entails assigning a prescriptive priority level to each of the HIV/AIDS programs offered indicating what the priority level ought to be for each program. Each program is also assigned a current priority level relating the level of priority currently given to each program. The highest level is 1, 2 is the next highest level, etc. and each level should only be used once. The levels are ordinal ranks and do not express a quantitative measure. The difference between prescriptive and current priority levels of each program is used in the final step to determine if programs are over- or under-funded. Priority levels should be determined by a consensus among all qualified respondents. If consensus cannot be reached, priority setting can be mediated by vote or by seeking expert opinion.Current priority levels should be set in view of the situation analysis and the user's perception of the target population needs, the programs' current clients and the program outcomes. Prescriptive priority levels can be elicited using the following two questions:1) Hypothetically, if $10,000 were available, which of the HIV/AIDS programs offered would you put it towards? Rank the answer as 1 and consider the remaining programs only.2) Hypothetically, if $10,000 were available, which of the remaining HIV/AIDS programs offered would you put it towards? Rank the answer as the next highest priority and consider the remaining programs only. Repeat this question until all HIV/AIDS programs are ranked.If priority setting is chosen as the rational method of resource allocation, it is assumed that actual levels of spending for each program are unknown. Current priority levels should be based on information collected in the situation analysis including program utilization. Assigning current priority levels consists in ranking the HIV/AIDS programs offered relatively according to the current priority given to each program.Several approaches can be used to define an equity-based heuristic allocation of HIV/AIDS resources. We define equity as an allocation proportional to the maximum allocation to each program within the planning horizon. The maximum allocation can be based on the absorptive capacity for an intervention, or, it can be calculated as the product of the unit cost of an HIV/AIDS program and the maximum number of people eligible for that program within the planning horizon. The information necessary to establish the maximum allocation is program-specific. For example, the maximum allocation to ART depends on the number of AIDS cases in the population and the annual cost of an ART regimen, while the maximum allocation to VCT depends on the adult population targeted and the unit cost of VCT. The equity allocation consists of partitioning the total budget proportionally according to the maximum allocation to each program. The difference between the equity allocation and the current allocation to each program is the main output used in the final step.An equity-based heuristic allocation of HIV/AIDS resources is recommended if the organization values the notion of fairness associated with equity above the notion of efficiency associated with optimization, or if cost-effectiveness data for the programs considered are not available.This approach to resource allocation requires all data outlined in the situation analysis and uses cost-effectiveness ratios to maximize health outcomes. Cost and outcome data for the HIV/AIDS programs are used to determine the cost-effectiveness ratios. However, if cost or outcome data are not available, then cost-effectiveness ratios may be identified through literature searches. The denominator of the cost-effectiveness ratios should be expressed in disability-adjusted life years (DALYs) or some other common measure of outcome.The optimization problem is then formulated as a linear program where the objective function aims to maximize the total number of DALYs gained, subject to a total budget constraint. The decision variables are the amounts to invest in each of the HIV/AIDS programs. There may also be maximum and minimum funding levels for each program. This allocation problem is equivalent to a knapsack problem and is easily solved by selecting programs in order of their cost-effectiveness ratios until the budget is exhausted . SensitiIn this last step, the background color of program nodes in the influence diagram drawn in Step 2 are used to highlight the output of Step 3. The background color of program nodes are set to bright green, light green, light red and bright red depending on whether a program should receive significantly more, slightly more, slightly less or significantly less funding, funding than the current allocation.Program nodes with matching coloured incoming arcs indicate that the influencing factors are a facilitator to the resource allocation objective while program nodes with mismatched coloured incoming arcs indicate that influencing factors act as a barrier to the objective set by the resource allocation model.Recommendations for improving the allocation of resources to HIV/AIDS programs are not automated. Rather, S4HARA assists in the formulation of actionable recommendations intended to improve HIV/AIDS resource allocation by creating a comprehensive picture highlighting the influencing factors that work either towards or against the solution derived in Step 3. The user examines the diagram in Step 4, detects the barriers and facilitators and identifies their source. The way these sources act as an impediment or an endorsement to an improved allocation must be interpreted. The user can then formulate actionable recommendations to alleviate the barriers and use the facilitators to encourage the allocation of resources.We illustrate the use of S4HARA with an example based on the kwaDukuza Primary Health Care (PHC) clinic. The municipality of kwaDukuza has a population of 170,000 and is located on the Indian Ocean coastline in the south-east of South Africa, near Durban.As part of a previous case study, we conducted 35 key informant interviews and collected documents relevant to HIV/AIDS programs and budgets in kwaDukuza over a six-week period during March and April, 2005 . InterviIn 2004, the antenatal HIV prevalence rate in kwaDukuza was estimated at 40% [Demographic information on the municipality of kwaDukuza and data on the clinic and its HIV/AIDS programs were collected . The kwaAs of April 2005, six HIV/AIDS programs were offered at the clinic: voluntary counselling & testing (VCT), a prevention measure aimed at getting people to know their HIV status; antiretroviral therapy (ART) administered through a nearby hospital; condom distribution; short course antiretroviral treatment for the prevention of mother-to-child transmission (PMTCT); treatment of sexually transmitted infections (STIs), used to decrease the probability of HIV transmission; and a "wellness" program intended to prevent and treat opportunistic infections (OI) in people living with HIV/AIDS.Annual data on the utilization of HIV/AIDS programs at the kwaDukuza PHC clinic for the year 2004 are summarized in Table National guidelines for the initiation of antiretroviral therapy include a CD4 cell count of less than 200 per cubic millimetre of blood. Of the patients seen by nurses or HIV/AIDS counsellors in the wellness program, 15% had their blood drawn for CD4 cell count testing. Of those tested, 38% had a CD4 count below 200 and 65% of those were referred for antiretroviral therapy. The public ART program in the municipality of kwaDukuza began in April 2004 and is administered by the main hospital located near the kwaDukuza PHC clinic. As of March 2005 there were 540 patients in kwaDukuza receiving ART through the public health system.The screen captures in Figures We proceed with an evaluation of all possible combinations of programs and factors, drawing arcs wherever applicable. We use thin and thick arcs to represent minor and major influences. The final influence diagram is illustrated in Figure In this step, the user selects and applies one of three approaches to HIV/AIDS resource allocation. For the sake of demonstrating the use of S4HARA, we outline the application of each approach in the subsections below. Results of the three approaches are described with the help of S4HARA screen captures reflecting the completed allocation.Figure Prescriptive priority fields were assigned based on the elicitation method outlined earlier. Results of the situation analysis and knowledge of current processes at the kwaDukuza PHC clinic helped determine the Current priority fields.According to the results highlighted, VCT and condom distribution should receive slightly more resources and the ART program should receive significantly more resources. These additional resources can be reallocated from the three other programs.Figure The maximum allocation to each program assumes a time horizon of one year and is the product of the maximum number of people that could be reached by a program and the unit cost of the program. For a given HIV/AIDS program, the current allocation is the product of the program utilization and the unit cost of the program. Program utilization rates were summarized in Table The results highlighted in the difference row indicate that VCT, ART, condom distribution and the treatment of STIs should receive a greater share of the available budget while the remaining two programs should receive less funding. Although these results may seem unfair to some population subgroups, they may represent improved distributive justice to others because the resources are allocated to the HIV/AIDS programs on the basis of equity.Data requirements for optimizing the allocation of resources to the HIV/AIDS programs include: cost-effectiveness ratios; minimum and maximum funding levels for each program; current allocation to the programs; and a total budget constraint. The kwaDukuza PHC clinic does not conduct economic evaluations so cost-effectiveness ratios for HIV/AIDS programs in similar settings were identified from the secondary sources ,26,42,43The optimal allocation of resources to the HIV/AIDS programs offered at the kwaDukuza PHC clinic is shown in Figure As well, we limited the allocation to each program using an upper bound set as the product of the unit cost and the maximum possible usage for each program. For example, the upper bound to the condom distribution program is set as the product of the cost per male condom distributed and the maximum number of condoms that can potentially be distributed by the clinic in a year. According to the unit cost data in Table The background color of fields in the difference row is highlighted in green when a program's share in the budget should be increased to meet the optimal allocation. It is highlighted in pink when a program's share should decrease slightly, while it is highlighted in red when a program's share should decrease by more than 10% relative to the current allocation.The optimal allocation suggests that condom distribution and the wellness program should receive a greater share of the available budget and the ART program should receive a significantly smaller share. Since the average cost per DALY saved for the condom distribution and wellness programs is less than that of the remaining programs, then allocating funds to condom distribution and wellness is a more efficient use of resources. For example, it is more cost-effective to gain a DALY by spending $4.60 on condom distribution rather than gain a DALY by spending $55.56 on VCT , and by a minimum investment in (4) where it is assumed that mini ≥ 0. This linear optimization model is equivalent to a knapsack problem and is easily solved [The decision variables y solved .To begin, we estimate the kwaDukuza PHC clinic HIV/AIDS program budget for the year 2004 using method "A". We then estimate the kwaDukuza PHC clinic HIV/AIDS program budget for the year 2004 using method "B" and compare the result to that of method "A".Unit costs of HIV/AIDS programs are derived from a recent study of the impact of scaling up HIV/AIDS intervention programs in low- and middle-income countries . They arTo estimate the kwaDukuza PHC clinic HIV/AIDS program budget for the year 2004, we sum the expenditures on the different HIV/AIDS programs offered at the clinic. Spending on an HIV/AIDS program is the product of the program utilization rate and the unit cost of the program. Annual data on HIV/AIDS program utilization at the kwaDukuza PHC clinic for the year 2004 were obtained from clinic nurses and the information officer for the municipality of kwaDukuza. Table In South Africa, there are four levels of government: national, provincial, district and municipal. The province of kwaZulu-Natal is comprised of ten districts including the iLembe District. The municipality of kwaDukuza is one of four local municipalities in the iLembe District.In order to validate the total budget estimated using method "A", we use method "B" to estimate the HIV/AIDS budget and compare the outcomes. Method "B" consists of allocating part of the provincial HIV/AIDS budget to the kwaDukuza PHC clinic according to equity criteria.We gather HIV/AIDS spending data for province of kwaZulu-Natal (KZN), then estimate the total provincial HIV/AIDS budget for the fiscal year 2004–2005 at $71 million, see Table The population of kwaZulu-Natal is estimated at 9.5 million while the population of the district of iLembe is estimated at 577,000, or approximately 6% of the total ,46. If tThere are 25 primary health care clinics in the district of iLembe, each delivering HIV/AIDS programs. In 2004, a total of 1,088,546 patients visited these clinics, and 11.4% of those visits were made at the kwaDukuza PHC clinic. If the HIV/AIDS budget for district of iLembe is allocated to the primary health care clinics in the district kwaDukuza PHC clinic proportionally according to the number of visits, then the kwaDukuza PHC clinic's share of the budget would be 11.4% of $4.3 million or approximately $494,000. However, this estimate excludes $251,100 in expenditures for the ART program because the program is managed through a nearby hospital (see Table The HIV/AIDS budget estimate for the kwaDukuza PHC clinic using method "A" is approximately $716,000 while it is $745,000 using method "B". We conclude that the initial method used is valid in estimating the 2004 annual HIV/AIDS budget for the kwaDukuza PHC clinic.The maximum annual allocation to each of the HIV/AIDS programs is the product of the maximum number of people that can potentially be reached and the unit cost of the program. Unit costs are defined in Table AL conducted the primary field research, developed the model and wrote the first draft of the manuscript. GSZ and MWC participated in the design and coordination of the model. All authors read and approved the final manuscript.


For over 25 years, International AIDS Conferences have played a key role in the response to AIDS: by providing the research community with opportunities to share important scientific advances, by profiling both successes and failures in the response to AIDS, and by offering a unique platform for people working professionally in the HIV field to address critical issues before a global audience.Whether reporting on scientific breakthroughs, raising the profile of social justice issues, or highlighting gaps in the response, the conference has acted as a benchmark for the HIV field to assess progress and address both new and ongoing challenges to prevent, treat and control HIV.The XVII International AIDS Conference (AIDS 2008), held 3 - 8 August 2008 in Mexico City, was an opportunity for HIV professionals to explore the latest scientific research, best practices and programmatic experience in the global response to AIDS. It also provided participants with a variety of formats for structured dialogue and debate on a broad range of HIV issues, including how to use the evidence base, knowledge and skills of those working in HIV to influence political leaders to implement proven interventions, increase their commitment to the response to HIV, and be more accountable for their national and international commitments. AIDS 2008 organizers identified key issues to be discussed in advance of the conference, including:• Health systems strengthening, service models, integration with TB and sexual and reproductive health services, co-infections , maternal health, long-term care, mental health, palliative care, drug resistance, harm reduction, primary health care, and hepatitis C• Specific regional issues • Synergy of treatment and prevention; treatment as a tool for prevention • Respect and promotion of human rights and gender equality as a framework for all aspects of the responsehttp://www.iasociety.org/Default.aspx?pageId=147.While AIDS 2008 was notable for the diversity and scope of its programme, this supplement focuses on content areas in which important new research, other evidence or lessons learned were presented, as well as on issues that generated significant discussion, debate and controversy that are likely to have a substantial impact on the global response in the coming months and years. The supplement is adapted from a report released in English and Spanish several months following the conference: The AIDS 2008 Impact Report: Evidence to Action, available at The International AIDS Society (IAS) recruited a team of writers with content expertise relevant to the scientific, leadership and community programmes of the conference to draft a post-conference report. Writers attended conference presentations as well as satellite sessions, pre-conference meetings, the Global Village, the youth programme and other events and activities outside of the formal conference programme.The writers confirmed leads for relevant programme areas and scientific programme tracks prior to the conference, and met for daily briefings during the conference to discuss emerging issues, report on their findings and informal discussions with conference delegates, and adjust their itineraries as required. The writers met immediately following the conference to confirm the conference highlights and sessions that, based on their analysis and final rapporteur sessions, would likely have the most significant impact on the HIV field in the future and should therefore be reflected in the report.Each writer then submitted a report that was reviewed, edited, and combined into a draft report which was then peer-reviewed by experts in the field. The final English language report, The AIDS 2008 Impact Report: Evidence to Action was released in December 2008 . A SpaniAIDS 2008 demonstrated both the enormous progress and outstanding challenges in the global response to AIDS as the 2010 deadline for universal access nears. As the first International AIDS Conference to be held in Latin America, it served as a platform for a number of commitments made by political leaders across the region, both prior to and during the conference. From the commitment of the host country to fight homophobia and other barriers to meeting universal access targets within Mexico, to the regional commitments on HIV-related health, education and treatment issues, AIDS 2008 has had - and continues to have - an impact well beyond the five days of the conference itself.The focus in this supplement is on profiling the presentations, discussion and debate that are likely to have the most significant impact on the epidemic in advancing an evidence-based response to HIV/AIDS. The AIDS 2008 Impact Report: Evidence to Action reviews highlights from the conference programmes , programme activities, pre-conference events and other activities to assess their impact on the field.http://www.jiasociety.org/ or IAS Abstract Database http://www.iasociety.org.The purpose of the AIDS 2008 Impact Report and this supplement is to assist stakeholders in implementing the evidence-based policies and programmes required to achieve universal access to HIV prevention, treatment, care and support. Although it is always difficult to determine with precision the impact of a conference as large and thematically diverse as the International AIDS Conference, this report reflects the best analysis of the writers and reviewers who attended the many sessions, satellites and affiliated events of AIDS 2008. Session codes are included in each figure and citation to facilitate searches for the source presentation on either the JIAS Abstract Database The supplement is contains six articles, each of which includes an analysis of the implications and potential impact of the major developments reported at AIDS 2008 in the areas of research, programme development, policy and advocacy.A brief review of global epidemiology and current challenges in assessing the incidence and prevalence of HIV, focusing on HIV surveillance and other strategic health information related to key populations .An analysis of new evidence presented in Track A of the Scientific Programme, as well as in related sessions, activities and affiliated events .An analysis of new evidence presented in Tracks C and D of the Scientific Programme, as well as in related sessions, activities and affiliated events .An analysis of new evidence presented in Tracks D and E of the Scientific Programme, as well as in other related sessions, activities and affiliated events .A review of the current response to the epidemic in the six regions, as well as a discussion of major lessons learned presented at AIDS 2008, and an assessment of the challenges, opportunities and future policy and advocacy priorities within each of these regions:▪ Asia and the Pacific Islands▪ Eastern Europe and Central Asia▪ Middle East and North Africa▪ Sub-Saharan Africa▪ Caribbean▪ Latin AmericaInformation presented in this article is drawn primarily from the Leadership and Community Programmes, as well as related programme activities and affiliated events .A review of major discussions at AIDS 2008 regarding how to improve efforts to track progress and strengthen accountability in the global response to AIDS, focusing particularly on strategies to enhance the role of the conference as an accountability mechanism .Specific programmes and initiatives are included in each article to illustrate both successes and challenges in research, programme rollout, policy and advocacy.The most important takeaway message from the conference is that a combination of insufficient resources, unmet commitments and structural barriers are preventing the full implementation of evidence-based prevention, treatment and care interventions. AIDS 2008, perhaps more than any previous International AIDS Conference, brought a renewed focus on the legal and human rights issues faced by vulnerable and most at risk populations both in generalized and concentrated or low-level epidemics.The evidence and experience from the conference were unequivocal in their message: until leaders in both government and civil society are able to separate personal morality and political expediency from the evidence-based interventions required to halt and begin to reverse this epidemic, universal access targets will not be met.The IAS hopes this supplement will be a useful resource for HIV professionals working in every sector of the response to AIDS, and that it will become a powerful tool used to strengthen the response to HIV/AIDS around the globe.Rodney Kort is an independent consultant contracted by the International AIDS Society for the purpose of preparing the AIDS 2008 Impact Report and adapting it for publication in the Journal of the International AIDS Society.


The current study's goal is to characterize the robustness of biofilm antibiotic tolerance to medically and industrially relevant culturing perturbations. By definition, robust systems will return similar, predictable responses when perturbed while non-robust systems will return very different and potentially unpredictable responses. The predictability of an antibiotic tolerance response is essential to developing, testing, and employing antimicrobial strategies.Biofilms are ubiquitous. For instance, the majority of medical infections are thought to involve biofilms. However even after decades of investigation, the Escherichia coli colony biofilms was tested against beta-lactam and aminoglycoside class antibiotics. Control scenario tolerances were compared to tolerances under culturing perturbations including 1) different nutritional environments 2) different temperatures 3) interruption of cellular quorum sensing and 4) different biofilm culture ages. Here, antibiotic tolerance was defined in terms of culturable biofilm cells recovered after a twenty four hour antibiotic treatment.The antibiotic tolerance of Colony biofilm antibiotic tolerances were not robust to perturbations. Altering basic culturing parameters like nutritional environment or temperature resulted in very different, non-intuitive antibiotic tolerance responses. Some minor perturbations like increasing the glucose concentration from 0.1 to 1 g/L caused a ten million fold difference in culturable cells over a twenty four hour antibiotic treatment.The current study presents a basis for robustness analysis of biofilm antibiotic tolerance. Biofilm antibiotic tolerance can vary in unpredictable manners based on modest changes in culturing conditions. Common antimicrobial testing methods, which only consider a single culturing condition, are not desirable since slight culturing variations can lead to very different outcomes. The presented data suggest it is essential to test antimicrobial strategies over a range of culturing perturbations relevant to the targeted application. In addition, the highly dynamic antibiotic tolerance responses observed here may explain why some current antimicrobial strategies occasionally fail. Cellse.g. ,4). Thise.g. -7.et al. [e.g. [The ubiquity of biofilms and their associated financial costs have inspired intensive antifouling efforts. A widely used anti-biofilm approach is to impregnate surfaces with antiseptics or antibiotics . The et al. ,11 concll. [e.g. ), the fae.g. [The current study aims to characterize colony biofilm antibiotic tolerance as a function of culturing conditions. The colony biofilm model is a widely adopted culturing system which possesses most features included in the numerous attempts to define a biofilm including: high cell density, extracellular polymeric substance, chemical gradients, spatially dependent microbial activities including slow growth, and reduced susceptibility to antibiotics e.g. ,13-16). -16. e.g.e.g. ,18. BiofTo our knowledge, this is the first time robustness analysis has been applied to biofilm antibiotic tolerance. Antibiotic tolerance is at the heart of many practical challenges related to unwanted biofilms. Being able to predict biofilm antibiotic tolerance as a function of culturing perturbations is essential for rationally designing and evaluating antimicrobial strategies. The presented results shed insight on the varying success rates of common anti-fouling strategies like antibiotic impregnated coatings and provide a template for improved antimicrobial testing schemes.Biofilms often exhibit very different antibiotic tolerances than planktonic cultures -4. To in10 reduction in cfu's per biofilm while ampicillin resulted in only a one log10 reduction in cfu's per biofilm  medium at 37°C. These antibiotics were highly effective against planktonic cultures reducing colony forming units (cfu's)/ml by 6 to 9 orders of magnitude Fig. . The biofilm Fig . Subsequfilm Fig . Just prThe results reinforce the concept that biofilm cultures can behave very differently from planktonic cultures and trends from planktonic cultures may not be relevant to biofilm cultures. Considering the well established importance of biofilms in medical infections, it is essential to test antimicrobial strategies against relevant microbe growth conditions.Surfaces susceptible to microbial colonization are often subjected to changing nutrient levels. For instance, a central venous catheter would experience different blood glucose levels based on patient activity, diel feeding schedules, or medical conditions like diabetes. Industrial food preparation surfaces could experience different nutrient loads based on worker schedules. The effect of nutritional environment perturbations on biofilm antibiotic tolerance was assayed to determine if antibiotic efficacy would be predictable.10 decrease observed in the absence of glucose. In the presence of glucose, ampicillin produced a 7 log10 decrease in cfu's per biofilm. For comparison, ampicillin produced a one order of magnitude reduction in cfu's per biofilm when grown on LB only. Just prior to antibiotic challenge, the biofilm cultures grown on LB + glucose contained 8.9 ± 0.1 log10 cfu's/biofilm while the LB only cultures contained 9.3 ± 0.1 cfu's/biofilm. Changes in antibiotic tolerance were not likely due to different cell densities as reported with planktonic S. aureus cultures [10 and 7.8 ± 0.2 log10 cfu/ml for the LB + glucose and LB only cultures respectively.Perturbing the nutritional environment by adding 10 g/L glucose to LB medium produced a large change in colony biofilm kanamycin and ampicillin tolerance Fig. . In the cultures . InteresE. coli [The glucose effect was analyzed to determine what magnitude of perturbation was required to elicit the observed antibiotic tolerance changes. Five glucose concentrations were tested Fig. . The bioE. coli .The effect of glucose on antibiotic tolerance was expanded to test other common hexoses found in the human diet including the glucose isomer fructose, the more reduced sorbitol, and the more oxidized gluconate. All tested hexoses had effects analogous to glucose and made the biofilm cultures more susceptible to ampicillin Fig. . ExperimE. coli strains unable to utilize glucose were constructed by sequential deletion of the ptsG, ptsM, glk, and gcd genes using the KEIO gene knock-out library and P1 transduction methods . The glucose negative cultures did not respond to glucose perturbations; antibiotic tolerance did not change significantly between the presence and absence of glucose  relevant to many food items, industrial settings, and the external surfaces of implanted medical devices like catheters. The temperature of 42°C was selected to represent the elevated temperatures associated with pyrexia.Antibiotic tolerance changed with some temperature perturbations. At 21°C, kanamycin and ampicillin reduced cfu's/biofilm by 6 to 9 orders of magnitude Fig. . This rea priori. In addition to considering nutrient environment, this data suggests it is critical to know if an antibiotic treatment will be effective over a device's operational temperature range.The biofilm antibiotic tolerance response is not robust to perturbations in temperature. Changes in antibiotic tolerance are not necessarily predictable e.g. [e.g.[Bacteria can communicate with other organisms and can sense properties related to their surroundings using small soluble molecules in a process termed quorum sensing (QS). QS has been associated with the multicellular coordination of many microbial behaviors including pathogenicity and biofilm formation . Com.g. [e.g., reviewe.g. [e.g.). The efE. coli AI-2 QS gene deletion mutants was constructed to act as proxies for QS interference strategies targeting different aspects of AI-2 QS. The strains lacked key enzymes in AI-2 synthesis (ΔluxS), phosphorylation (ΔlsrK), regulation (ΔlsrR), and degradation pathways (ΔlsrF) (reviewed in [A set of iewed in ). The AIiewed in .E. coli K-12 MG1655 AI-2 QS mutants were constructed using the KEIO gene knock-out library and P1 transduction methods . The strains were characterized for planktonic and biofilm growth characteristics. Mutant and wild-type planktonic growth rates were nearly identical . Colony biofilm growth rates and final cell densities also showed no statistical difference . The AI-2 production profiles for planktonic cultures can be found in Additional file The luxS), regulation (ΔlsrR), or degradation (Δlsrf) increased ampicillin antibiotic tolerance. These cultures had 6 orders of magnitude more cfu's/biofilm after ampicillin treatment as compared to both wild-type and AI-2 phosphorylation (ΔlsrK) mutants. Additional experimental data regarding the effects of AI-2 gene deletions on antibiotic tolerance can be found in Additional file luxS mutant demonstrated an altered glucose catabolite repression response.Perturbation of AI-2 QS did not result in any significant changes in biofilm antibiotic tolerance when cultured at 37°C on LB only medium Fig. . When thE. coli biofilm antibiotic tolerance is robust to perturbations in AI-2 QS when grown on LB at 37°C however; the response becomes non-robust in the presence of glucose. The results indicate that QS interference can have unpredictable results that change as a function of targeted gene and culturing perturbations.The results suggest The data presented in Figs. 1, 2, 3, 4, 5, 6 and 7 were collected from biofilm cultures grown for 6 hours prior to the 24 hour antibiotic challenge. At 6 hours, the biofilm cultures were still growing  and  and e.g.e.g. . The proe.g. -39. Manye.g. -42.E. coli cAMP-CRP catabolite repression system through undetermined mechanisms [Based on the changes in antibiotic tolerance as a function of glucose, the current data suggests the cAMP-catabolite repression protein (cAMP-CRP) circuit may play a role in antibiotic tolerance. Intracellular cAMP levels are widely reported to change in the presence of sugars ,44. Theschanisms ,46. InteThe cultures grown at 21°C were generally more susceptible to both kanamycin and ampicillin. At this temperature, there was no observed difference in antibiotic tolerance as a function of glucose perturbations. The absence of a nutritional effect suggests the cAMP-CRP regulatory system is influenced by temperature. Additional cellular processes could also be contributing to the observed behaviors including temperature dependent changes in multidrug pump expression , temperaluxS based AI-2 QS system can increase, decrease, or have no effect on biofilm formation depending on the organism or strain [Pseudomonas aeruginosa [Staphylococcus aureus and Staphylococcus epidermidis can make the microbes more resilient to antibiotic treatments  implying a disruption of a portion of the glucose repression circuit. The ΔluxS strain did display catabolite repression based diauxic growth. The strain was grown on defined M9 medium containing both glucose and xylose. Like the wild-type strain, the ΔluxS strain preferentially consumed glucose (data not shown). The data from this study do not support pursuing a strategy of AI-2 quorum sensing interference as an antifouling approach with E. coli.Interrupting AI-2 QS had varied and unpredictable effects on antibiotic tolerance. A growing body of research suggests different organisms use QS for different purposes and that QS effects can be quite diverse. For instance, a recent review highlights that the r strain . While aruginosa ,48, acceiewed in ). The cuRobustness analysis revealed that colony biofilm antibiotic tolerance is very sensitive to culturing perturbations. These tolerance responses can vary based on single or aggregate perturbations and are, in many cases, not predictable. The collective data represents both challenges and opportunities for the rational design of anti-biofilm strategies. The data demonstrates that biofilms can be countered effectively with some antibiotics if the appropriate conditions are applied however, if inappropriate conditions are applied, the efficacy of the treatment can be negated. The results indicate it is essential to evaluate antimicrobial strategies over a range of perturbations relevant to the targeted application so that accurate predictions regarding efficacy can be made.E. coli K-12 MG1655 gene deletion mutants were constructed using the KEIO mutant library and P1 transduction techniques [E. coli cultures were grown in low salt Luria-Bertani (LB) broth with or without different substrate supplements. When added, the supplements were autoclaved separately from the LB medium. The average starting pH of the medium was 6.8. All antibiotics were utilized at a final concentration of 100 ug/ml. The tested antibiotics had different molecular weights so this mass concentration represents a different molar concentration for each agent. Culturing temperatures ranged from 21 to 42°C depending on experiment.chniques ,51. E. c600 = 0.1). The culture is grown for 6 hours on untreated plates of the desired medium composition. After the initial growth phase, the biofilm is aseptically transferred to either a treated or a control plate where it is incubated for an additional 24 hours. The nutrients and antibiotics enter the biofilm from below the membrane. Antibiotic penetration of colony biofilms has been studied expensively suggesting the agent readily moves throughout the biofilm [The colony biofilm culturing method has been described previously ,7,52,53. biofilm .For planktonic antibiotic tolerance experiments, 50 ml cultures were grown exponentially for six hours with shaking  at 37°C in untreated medium (with or without 10 g/L glucose). The cells were collected using centrifugation . The cells were resuspended in fresh medium of noted composition and cultured for another 24 hours at 37°C with shaking (150 rpm). The viable cell counts were determined using serial dilutions and the drop-plate cell enumeration method . All culE. coli K-12 MG1655 gene deletion mutants were constructed using the KEIO knock-out library, P1 transduction methods, and wild-type E. coli strain MG1655 [n MG1655 ,51. The Statistical significance was determined using p-values from unpaired T-tests of experimental and control samples. All error bars represent standard error of 3 to 8 replicates.cfu: colony forming unit; QS: quorum sensing; LR: log reductionConception and design of experiment: TRZ, RPC. Acquisition of data: TRZ, HB, JLR, LJT. Analysis and interpretation of data: TRZ, PSS, RPC. Drafting the manuscript: PSS, RPC. Revising the manuscript critically for intellectual content: TRZ, HB, PSS, RPC. Final approval of published version: TRZ, HB, JLR, LJT, PSS, RPC.Supplementary culture data. This file contains supporting planktonic and biofilm culture.Click here for file


For the outcome evaluation, a survey of J2J attendees and evaluations of the program lectures by attendees were performed in chronological order to determine their perception on usefulness of the program.Overall, the J2J curriculum is successful in providing journalists with a clear understanding of the current HIV/AIDS medical research objectives and issues with most journalists reporting an increased ability to better investigate and disseminate accurate information on this subject. Furthermore, the journalists surveyed reported positive community responses directly as a result of the J2J training.The J2J program helps to increase global awareness of pertinent HIV/AIDS concepts. Through this professional development strategy, journalists from around the world may help to amplify efforts to prevent new HIV infections and quench the dissemination of inaccurate information and folklore. The detrimental impact of the acquired immunodeficiency syndrome (AIDS) on global health has continued since the first reported cases of human immunodeficiency virus (HIV) infection in the early 1980s. Thus, facilitating worldwide awareness of HIV/AIDS is of paramount importance in public health campaigns aimed at prevention of new infections.The dissemination of HIV information is a task largely undertaken by community health care workers, advocacy groups, and journalists. Of these professions, journalists probably are the most able to efficiently disseminate pertinent information on a global scale ,2 and muThus, effective communication between HIV/AIDS research groups and journalists from around the world is essential if we are to improve the understanding of HIV/AIDS worldwide. This was the premise that led to establishment of a Journalist-to-Journalist (J2J) HIV/AIDS training program as a component of the International AIDS Conference in 2002.The program was developed as a satellite meeting by the National Press Foundation (NPF) in advance of the main conference, the purpose of which was, "preparing selected journalists to cover the International AIDS Conferences, and then to continue to cover the subject at a higher level than previously imagined." It is important to note that the journalists accepted into the program did not have specialized scientific training.The program was first launched at the Barcelona International AIDS Conference in 2002, and has been held three other times since then in Bangkok in 2004, Toronto in 2006, and Sydney in 2007. Fellows are invited to participate based on their journalistic competence and experience after submitting a successful application to attend. Preference is given to journalists from developing countries since such areas are considered to be most at risk for new HIV infections and because journalists from developing countries are often least able to afford the costs involved in participating in such a conference.The invited individuals had to be journalists or communicators in any field, had to have previously written or broadcast about HIV/AIDS and have to had the support of their supervisors to attend. They also needed had to supply a printed or video version of a piece that they had done in the field of HIV/AIDS. After these criteria had been met, a second evaluation involved ability to speak English, the type of medium used the candidate and the country of origin so that as many countries or regions as possible would be represented. Financial assistance for travel, lodging, registration, and meals for the duration of the J2J program and conference was provided by the program that is funded by a grant to the NFP by the Bill and Melinda Gates Foundation.Thirty nine of 74 journalists who were invited attended the Barcelona J2J program, but this number dropped to only 9 of 75 for the Bangkok conference primarily because poor communications from the conference organizers to members of the journalistic community. In contrast, 95 of 105 invited journalists attended the Toronto conference and 42 of 44 invited journalists attended the Sydney program.Researchers in each of the basic, social and clinical sciences strongly agree with the crucial role that journalists can play by accurately informing the public on issues that relate to the global HIV/AIDS epidemic -5. PreveThe authors of this report , all very familiar with the HIV/AIDS scientific literature, were asked to evaluate the J2J program in order to:a) assess the relevance of the curriculum content and didactic quality of information delivered to journalists  and,b) explore the effects of such programs on reporting of HIV/AIDS related information .Our secondary objectives were toc) assess journalists' perceptions as to how this training program affected their coverage of HIV/AIDS, andd) determine whether the program had resulted in improved provision of information to communities about truths and misconceptions about HIV/AIDS.Our team was provided by the J2J program organizers with the following material for evaluation of the program:a. E-mail addresses of all participant journalist fellows who possessed such an address.b. A large sample of news stories on HIV/AIDS written by journalists who attended the training sessions and conferences.c. Evaluation reports of the Bangkok and Barcelona programs previously prepared by the National Press Foundationd. Evaluations by journalists Sydney program.e. Data accessible online from a number of slide presentations delivered in each of the following J2J training programs . Presentations from Sydney also included voice recordings of scientific presentations.Careful study of the J2J curriculum (included as part of each conference program) was completed by at least two evaluators. Each evaluator issued a descriptive statement on the completeness of the program by answering the following questions:Is the content of the J2J curriculum suitable and complete?What key subjects were lacking?What subjects might be excluded?After each individual evaluation, a group discussion resulted in agreement on the completeness of the curricula. In the same fashion, a sample of 24 slide presentations (available online) were evaluated for relevance, complexity, organization and quality of slide presentation. Each slide presentation was scored using the following scale: 1 = poor, 2 = fair, 3 = good, 4 = excellent.In addition, journalists' evaluations of the Sydney conference J2J program (n = 42), which had used the same scoring scale, was taken into consideration.To establish the benefits of the program, two types of analyses were performed. First, a random sample of 39 news reports (of 84 available in English or with an accompanying English translation) completed by journalists who participated in any of the J2J programs was examined for relevance and accuracy . These 39 news reports represent a sample of 46% of the total of reports available in English. Each report was reviewed by at least two members of our team. In cases of non-agreement, which were very rare, the senior author of this paper made a definitive assignment of grade.A short survey in the form of a questionnaire  adequately allocated time for journalists to become informed of the diverse needs of PLWHIVs, including the issue of HIV-related stigma. Journalists who attended this series of seminars acknowledged the opportunity to speak to HIV/AIDS activists.Topics that were determined to be insufficiently represented at this J2J satellite included:1) An introduction to principles of scientific research.2) Development of tools that enable journalists to ask the right questions about epidemiologic research.3) Discussion of how the needs of PLWHIVs might be met by local government and non-government organizations.Also lacking was a specialized seminar on how to access HIV/AIDS data on prevalence, trends, projections, public programs, as well as obstacles toward implementing HIV/AIDS health programs in various countries.It was pointed out that assessments of local health agencies, government and non-governmental organizations (NGOs) would have been beneficial.Some of the Bangkok J2J delegates felt that the biomedical research lectures presented at the J2J Satellite were burdened with excessive detail. There were also requests for implementation of country-specific J2J professional development curricula.The overall J2J satellite offered a rich epidemiological and cultural experience. On the other hand, the Toronto J2J curriculum was felt to be lacking in seminars about clinical research methodology and on how to decipher scientific jargon commonly used among HIV/AIDS scientists. Presentations on HIV prevention were appreciated by the delegates as were lectures on behavioral and medical interventions.The Sydney IAS 2007 conference focused primarily on biomedical research and the J2J program prepared for this through a comprehensive curriculum that spanned several days before the conference. The J2J organizers also offered comprehensive discussions on particular issues that were anticipated to be especially important. An introduction to scientific jargon was presented in the context of a session on vaccines and microbicides. A more general introduction to scientific jargon might also have proved useful. The reviewers felt that an informative session describing how certain scientific results are chosen for presentation at international conferences should have been included and also a session on how decisions are made by individual scientists to present their work.In all J2J programs a paucity of participants from the private sector was evident. This is despite the fact that the drug companies are well represented at every IAS conference. It therefore seemed strange that this sector was not better represented in the J2J program.A post-conference follow-up meeting was absent from the program. Such a meeting would serve to reinforce understanding of key issues/topics and enable journalists to clarify what they have or have not understood.At the Sydney conference, we gained access to journalists' evaluations of each presentation in the context of the J2J program. On average, journalists gave grades of excellent or good to fourteen of the sixteen presentations delivered. Thirteen of the sixteen lecturers (76%) were evaluated by attendees as good or excellent. The average grade for all lecturers was 3.08 which was comparable to previous averages from Barcelona and Bangkok, i.e. 3.1 and 3.19, respectively (maximum score is 4.0). Overall evaluations by journalists were good or excellent for each topic covered. Only three of thirteen presentations failed to score in the excellent range.Our committee evaluated 24 J2J presentations available online on the basis of relevance, complexity, organization, slide quality and background information. Only two presentations had an average score less than 3. The area in which presentations were frequently weak was in slide quality . The content of all presentations, except two, was considered to be highly relevant.A comparison of the evaluations by journalists of the Sydney J2J sessions with our own evaluations of the same sessions revealed concordant excellent grades for five of seven lectures, while the other two were only discordant between good vs. excellent grades. This is consistent with the observation that the presentations were of high caliber in regard to the objective of educating journalists.Thirty-nine news reports from those that were written in English or had an accompanying English translation were randomly chosen for review by two evaluators. In almost all cases, the reports were from journalists working on developing countries Figure .Those in the categories of excellent and good were grouped together and the extent of agreement between the evaluations was determined. Discordant evaluations were adjudicated by an additional reviewer, if necessary. Reports in English were deliberately overrepresented in the sample analyzed, as the reviewers were mainly English-speaking. In almost all cases, the reports were from journalists working in developing countries , thirty-three of the 39 (84%) reports from all of the J2J sessions evaluated were found to be good or excellent. The topics discussed in these journalists' reports are summarized in Table We emailed a request to complete an online survey to 160 journalists. Seventeen e-mail messages did not reach recipients. Forty-two journalists completed the survey.The respondents were almost unanimous in judging that the J2J program was very useful and 79% of them have increased their reporting of HIV/AIDS since the conference . This is a key area for consideration, since the public is poorly informed in general about the roles played by drug companies in scientific research and may be easily seduced by 'conspiracy theories' that attribute false motives to companies. Responsible reporting on relationships between the private and public sectors, including academia, may help to quench misconceptions.Finally, presentations of exemplary work by leading world-class HIV/AIDS journalists might also enhance the J2J curriculum. Less experienced journalists might be paired with more experienced 'mentor' journalists from their own countries, as well as from developed countries, for in depth discussions. Former fellows might also be able to share experiences with new fellows and help the latter to improve their communications skills. There could then be a 'trickle-down effect' if journalists were to conduct smaller, albeit less ambitious J2J-like programs, in their own countries.The need for education of communities about HIV is evident. Several reports have documented insufficient knowledge in populations at risk of acquiring HIV infection -10. In tThe World Health Organization has stated that impact may vary, depending on the place and campaign, but that comprehensive mass media programs are valuable in helping to change HIV/AIDS-related behavior, at least among young people in developing countries . TherefoThe J2J program has an opportunity to engage in outreach to help direct and/or support international education campaigns through the networks that have now been established. A continuous and synchronized effort to promote education of communities through written publications and/or radio programs might be established using the broad human resource represented by the J2J program. The creation of material based on the J2J presentations and local replication of similar programs could be encouraged, and could also be carried out in languages other than English. Ongoing feedback from such efforts could then be used to improve the overall effort, which could be implemented and locally tailored to regional needs for use in subsequent initiatives.The response rate for the survey was only 26%, evidently raising the issue of bias. On the other hand, favorable grades were given to the j2j program by attendees who evaluated the program at previous conferences and these were consistent with the later grading found through the survey.Despite the heterogeneous educational background of the journalists attending the J2J program, we observed a high quality of accuracy and pertinence in the reports written by attendees. Altogether, these observations suggest a beneficial effect of the program on the communication skills of the journalists in the HIV/AIDS field. Nevertheless, a sample of reports by the journalists before the J2J session would have been ideal for comparison with those available after the session. Unfortunately, such information was not available to us.For future evaluations, and in order to accurately determine the effect of J2J on journalists' skills, it might be advisable to obtain and evaluate a baseline set of reports from the invited journalists before the session.Although we cannot definitively conclude that J2J improved skills in reporting of HIV/AIDS in general, the perception from attendees at the end of the each J2J program and those who responded to our survey were all positive suggesting that the goals of the program were realized.Usually, lack of response to a survey represents low motivation to spend time answering questions and not necessarily a negative perception of the issue involved. In addition, emails to contact journalists in developing countries might not be the best strategy for future surveys since internet access may be limited or unstable for a proportion of potential respondents.The J2J program of the National Press Foundation has accomplished its main goal of gathering journalists from around the world to be trained in how to better report HIV/AIDS news.Journalists have consistently indicated that the program is highly useful and that it enables them to cover and inform the public in a variety of areas: experiences of people living with HIV/AIDS, impact on society, the reasons for stigma, how to work toward destigmatization of HIV, hopes and limitations of current therapy including issues of drug access in developing countries, prospects for novel therapeutic and prevention initiatives, and the successes and failures of research and/or public health measures.Vital information in each of these areas needs to reach the general public, who will ultimately decide what it is important to pay attention to and in which areas to establish priorities.Journalist reports are an effective means of providing information on HIV awareness to vulnerable populations, hopefully helping to lower rates of infection and educating those who are infected by HIV to seek adequate help. Public awareness can help to guide public opinion and influence government policy in a positive way and to counter stigma, which is often a result of misperceptions about HIV/AIDS. Journalists play important roles in each of these areas and the J2J program has been key in educating journalists worldwide to do their jobs better.MAW was an invited speaker at the J2J Conference in Sydney.JLMC led in the study design, data analysis and manuscript preparation. CFI participated in the study design, data analysis and manuscript preparation. MN and SMS participated in review and evaluation of news reports and of the J2J program's curriculum. MAW participated in study design, evaluation of news reports, and manuscript preparation.Survey Questionnaire. The questionnaire used for the on-line survey.Click here for file


The authors discuss the "downstream" effects of AIDS on poverty, and the "upstream" effects of poverty upon acquiring HIV. It is often asserted that AIDS is at the core of a “vicious circle”, whereby the impacts of AIDS increase poverty and social deprivation, while poverty and social deprivation increase vulnerability to HIV infection. In examining this view, it is important to distinguish between what might be called the “downstream” effects of AIDS on poverty, and the “upstream” effects of poverty upon the risk of acquiring HIV.Generally speaking, there is a strong association between poverty and ill health—wealthier countries and wealthier individuals enjoy better health as measured by a variety of indicators such as life expectancy or incidence of waterborne diseases. Many researchers have had the same expectation about AIDS, which has often been described as a “disease of poverty” .There is one fundamental difference, however, between AIDS and other health problems generally linked with poverty. Unlike diseases such as tuberculosis and malaria, HIV is mostly transmitted through sex. This brings into play the economic perspective around reward and dependency, which influences the extent to which individuals are able to make and exercise choices about sexual behaviour. Recent evidence clearly indicates that AIDS is a disease of inequality, often associated with economic transition, rather than a disease of poverty in itself.Undeniably, more people live with HIV in poor countries than in rich ones. More than 60% of people living with HIV inhabit the world's poorest region: sub-Saharan Africa. Nevertheless, studies during the early stage of the epidemic suggested that HIV incidence initially occurred not amongst the poorest, but among better-off members of society in this region. A decade later, infections still appear more concentrated among the urban employed and more mobile members of society, and consequently the more wealthy groups, as can be seen in It is important to note that HIV prevalence is very high in all of the wealth quintiles—including quintile 1, the poorest . While there is abundant research that documents the mechanisms that lead from extreme poverty to HIV vulnerability , the datWhether the patterns observed in this part of Africa will also emerge elsewhere remains to be seen. In Asia, for example, epidemics have so far been mostly concentrated in sex workers (and their clients) and drug users, who are often very poor. Infection patterns are now influenced by rapid economic development, which has increased the movement of both men and women in search of opportunities within and across borders. And here, as in Africa, mobility correlates to higher rates of HIV infection.Many researchers now point not to poverty itself but to economic and gender inequalities and weakened “social cohesion”  as factohttp://www.transparency.org/policy_research/surveys_indices/cpi), and are regarded as having reasonably good governance. Meanwhile, some countries that have high levels of corruption according to this index, such as Kenya and Côte D'Ivoire, have lower—but still very significant—HIV prevalence, suggesting that inequality is a stronger predictor of HIV prevalence than poor governance. One possible consequence of this apparent association between inequality and HIV is that economic growth that is not pro-poor and that leads to greater income inequality may even fuel the HIV epidemic.One indication of the connection between poor governance and HIV is the clear pattern of association between income inequality as measured by the Gini coefficient and HIV prevalence across countries in sub-Saharan Africa—countries with greater inequality have higher HIV prevalence  For exWe can thus expect AIDS to impede efforts to reduce poverty. In high-prevalence countries such as Botswana, estimates have projected that the number of households living in poverty will increase at a rate that is 0.5% higher per year than if there were no AIDS . A smallThe epidemic is dramatically increasing the numbers of orphans, particularly in high-prevalence countries. More than 15 million children worldwide have been orphaned by AIDS—over 12 million of them in sub-Saharan Africa, overwhelming the capacity of social networks and traditional patterns of intergenerational dependency, and creating an uneducated, unsocialized, and often uncared-for generation .Companies in high-prevalence countries can also expect AIDS to decrease productivity and increase costs for recruitment and training, with the magnitude of these effects depending on the employment conditions and benefits offered by the company, the HIV prevalence in the workforce, and the skill levels of the employees most affected. A study in Africa has found widely varying HIV-related costs from 0.5%–10% of the total labour costs—which in some sectors would constitute a very significant proportion of company profit , and increased demands for health and other public services related to the epidemic.At a national level, the macroeconomic impact is expected to be relatively small when compared to that of other factors related to the global economic environment and the quality of economic management in affected countries. Most estimates making use of standard economic models in high-prevalence countries indicate a reduction of about 0.5%–1.5% in the gross domestic product (GDP) growth rate over a 10 to 20-year time frame compared to the situation without AIDS . The imSome researchers have drawn attention to the longer term potential for progressive weakening of human capital, and the lost transmission of knowledge and skills between generations. This is of particular concern given the increasing recognition that AIDS is a long-term phenomenon for which long-term strategies are required.Understanding both upstream and downstream interactions between AIDS and poverty is critical to understanding local and global epidemiological trends and patterns. Such an understanding is, in turn, vital to the development and implementation of effective strategies to prevent and treat HIV.Growing awareness of the economic aspects of the epidemic has helped catalyze greater political action on AIDS in recent years. For example, AIDS is the only health issue ever to become the subject of a United Nations Security Council debate or a Special Session of the UN General Assembly. It has been featured regularly at G8 meetings and regional summits in Africa, the Caribbean, and elsewhere. In more than 40 countries, National AIDS Programmes are led by the President, Vice-President, or Prime Minister.Political action has fuelled financial investment. Global expenditure on AIDS in low- and middle-income countries increased from $250 million in 1996 to an expected $10 billion in 2007.We are now beginning to see a return on this investment. Fewer people are becoming infected with HIV in almost all East African countries, in the Caribbean, in Cambodia, and in southern India. Almost 2.5 million people are now on antiretroviral therapy in developing countries—up from 100,000 five years ago. To build on this progress and ensure that it is sustainable, however, six elements are key.First, AIDS money has the most impact when strategies are based on the concept of “know and act on your epidemic”. UNAIDS' Practical Guidelines for Intensifying HIV Prevention [evention  provide evention .Second, a growing number of small-scale activities indicate the value of combining HIV programmes with poverty reduction initiatives. In Malawi, non-governmental organizations integrate HIV prevention into village banking programmes for women, and combine AIDS education with the provision of microfinance to groups of women through community banking programmes [ogrammes . In Nortogrammes . The chaThird, the provision of HIV treatment can help prevent poverty—and indirectly contribute to HIV prevention as well—by helping to break down stigma. A study in Kenya observed a rapid improvement in labour productivity among tea pickers in 12 months after starting antiretroviral treatment [reatment . Such fiFourth, development plans  must “pass the AIDS test”. Development initiatives must contribute to AIDS prevention and treatment in the communities they work in. The World Bank–supported Chad/Cameroon Pipeline Project, for example, supports HIV workplace interventions along the pipeline route—both for workers and for affected communities [munities .Social pFifth, both poverty reduction programmes and AIDS strategies must reduce vulnerability to HIV—particularly for women and young people. Doing so involves protecting human rights and tackling issues around social marginalization and stigma. The link between poverty, gender inequality, and HIV has prompted many institutions to talk about integrating gender and AIDS into development and poverty reduction strategies, but far more action is required [required . One obvSixth, addressing AIDS in the world's poorest countries and communities depends on increased and sustained international support, driven by high-level political will. Although it is ultimately the responsibility of all states to provide HIV prevention and treatment for all citizens, and to mitigate the impact of AIDS on the poor, many countries require international support to live up to these responsibilities, and are likely to do so for some time to come. Failure by donors to prioritise the provision of such support is likely to undermine the effectiveness of current and future efforts, and could also lead to the unravelling of progress already made.AIDS, it has been said, is exceptional  in termsAnother example of complexity is that the relationship between socioeconomic status and HIV varies considerably from country to country, reflecting differences in culture and traditions. Effective actions to tackle AIDS must directly address these specific factors—the inequalities—that drive HIV transmission in different contexts, and must overcome the obstacles to accessing treatment in different groups. .Complex problems famously require complex solutions. In this case, it is crucial to place AIDS squarely at the centre of all socio-economic development, and provide long-term, high-level domestic and international investment in HIV prevention and treatment in the world's poorest countries.


We used a link between cancer  and AIDS  registries in the United States to study whether nasopharyngeal carcinoma (NPC) was increased in the population with AIDS. There was no indication of a significantly increased risk up to or after the AIDS diagnosis, which argues against progressively failing immunity being important in the development of this malignancy.


The aim of the present paper is to study the potential involvement of the p15 gene in the evolution of TCCs. p15 mRNA expression was investigated by semi-quantitative RT-PCR in a series of 75 TCCs, 13 bladder cell lines and 6 normal bladder urothelia by semi-quantitative RT-PCR. p15 was expressed in the normal urothelium but p15 mRNA levels were significantly decreased in 66% of the superficial (Ta-T1) TCCs (P = 0.0015). In contrast, in muscle-invasive (T2-T4) TCCs, p15 expression differed widely between samples. p16 mRNA levels were also studied and there was no correlation between p15 and p16 mRNA levels, thus indicating that the two genes were regulated independently. Lower p15 expression in superficial tumours did not reflect a switch from quiescence to proliferative activity as normal proliferative urothelial controls did not present decreased p15 mRNA levels relative to quiescent normal urothelia. We further investigated the mechanisms underlying p15 down regulation. Homozygous deletions of the p15 gene, also involving the contiguous p16 gene, were observed in 42% of the TCCs with decreased p15 expression. No hypermethylation at multiple methylation-sensitive restriction sites in the 5́-CpG island of p15 was encountered in the remaining tumours. Our data suggest that decreased expression of p15 may be an important step in early neoplastic transformation of the urothelium and that a mechanism other than homozygous deletions or hypermethylation, may be involved in p15 down regulation.© 2001 Cancer Research Campaign  http://www.bjcancer.comThe


The HIV/AIDS epidemic in America is rapidly progressing in certain subpopulations, including African-American and Hispanic communities. Churches may provide a means for reaching high-risk minority populations with effective HIV/AIDS prevention. We report on a series of focus group interviews conducted with Utah clergy who primarily serve African American and Hispanic congregations.A total of three focus groups (two with Catholic clergy serving Hispanic congregations and one with protestant clergy serving African American congregations) were conducted with eleven participants, lasting approximately two hours each. Each focus group was audio-recorded and transcribed for analysis. Analysis of the data was conducted using a modified grounded theory approach.There were remarkable similarities in the attitudes and beliefs among all clergy participating in this study regarding HIV/AIDS and church-based prevention programs. All groups expressed concern about the diseases as a global epidemic and reported that the disease is highly preventable. Also, participants indicated a sense of responsibility to address the issues surrounding HIV/AIDS-related prevention, testing and care within their theological framework.HIV/AIDS prevention and care for the infected are seen as falling within the scope of religious organizations. Openness to expanding efforts in this regard was shared by clergy participating in this study. Approaching religious leaders with tailored approaches that respect the values and practices of their particular religions will be more effective than attempting to impose approaches that do not achieve this standard. After two decades of HIV/AIDS in America, the epidemic is rapidly progressing in certain subpopulations, including African-American and Hispanic communities. Adults and children in these communities have been disproportionately affected. According to the CDC surveillance reports for 2001, African-Americans and Hispanics together represent 57 percent of reported AIDS cases and 62 percent of reported HIV cases  as a problem.” However, the African American clergy stated that they knew of church members who were infected as well as members who had died from the disease. As such, African American clergy indicated more awareness and active engagement in addressing HIV/AIDS within their congregations.Both groups stated that members of their congregation engage in risky behaviors. They also discussed their belief that HIV/AIDS has a bigger impact on people outside of their congregation than on participating church members, and stated that those whose lifestyles put them at risk for HIV/AIDS may not attend or may feel ostracized from the church. Thus, they further indicated that outreach beyond their own church members was both necessary and part of their ministry. Included in this was a concern regarding HIV/AIDS among incarcerated individuals.All respondents professed compassion for those infected with HIV/AIDS and for those affected because of an HIV positive loved one. There was a distinction between teachings that condemn the behaviors and compassion for individuals engaged in these behaviors. When asked about current HIV/AIDS-related activities, the African American clergy discussed a number of established programs within their churches including HIV/AIDS information/awareness meetings, educational programs focused on youth, spirituality programs for those infected with HIV/AIDS, and outreach to prisoners and community members. The Catholic clergy discussed moral teachings targeted at high risk behaviors for youth prior to their Quinsañeras celebrations.Respondents were asked about the acceptability of a number of church-based HIV/AIDS prevention programs, and gave very similar answers. Both the Catholic and African American Christian clergy felt that sermons and youth services about abstinence and drug abuse, public workshops about HIV/AIDS prevention, support groups for people with HIV/AIDS and their family members, and outreach programs directed at people at risk for HIV/AIDS would be acceptable church-based activities. A number of participants stated that they would not discuss condom use or other non-abstinence-related prevention methods from the pulpit. Both groups felt that sermons and youth services about condom use, clean needle exchanges, and condom distribution would be unacceptable church-based activities.Some participants stated that discussion of such issues may arise during one-on-one interactions with church members or in church-sponsored activities outside of sermons. In each case, such comments were linked to concerns about balancing appropriate moral teaching with effective means of preventing infections. They were clear that such discussions needed to be handled with the utmost sensitivity and judgment.Ministers were eager to learn about means of improving their existing programs. Specifically, they were interested in learning more factual information about HIV/AIDS and developing programs that fit within their respective doctrines. They further discussed the need to be sensitive to doctrinal limitations, time constraints, and busy schedules in improving upon their current efforts. All were open to integrating their efforts with others addressing this epidemic as long as these same sensitivities were considered.With the continued emergence of HIV infections there is increasing evidence that preventive efforts are not sufficiently effective and that increased attention is needed to care for the infected. When addressing these issues, novel approaches such as church-based prevention programs may provide the means for increased success in both prevention and care. Our research indicates that religious leaders see themselves as having responsibility in addressing the HIV/AIDS epidemic. Further, they see themselves as a critical part of the multifaceted campaign to address HIV/AIDS related impacts.Specifically, clergy indicated that there are many ways in which their efforts related HIV/AIDS may be enhanced. From their perspective, collaboration with others that fit within the scope and boundaries of their ministries will likely lead to increased effectiveness in prevention and compassionate care. Further attention is needed for the development approaches to enhance clergy members’ capacity to be effective in their efforts as well as the design of evidence-based interventions that are consistent with clergy members’ primary ministerial responsibilities.Church-based programs may also be a means of reaching high-risk minority populations. Many outreach efforts are already targeting individuals at high risk, providing a natural platform from which to further extend HIV/AIDS related efforts. However, in the development of such programs, sensitivity to church doctrine, theological limitations, and cultural diversity are factors that must be addressed. With such consideration, HIV/AIDS prevention messages and promoting care for the infected can easily be incorporated into current church teachings and outreach programs.Academic and other social institutions have a role in working with religious organizations to integrate efforts as a means of creating synergy that can directly impact the HIV/AIDS epidemic and those infected. Specific programs can be designed and collaboratively implemented that combine the most current understanding of the HIV/AIDS biology and effective behavioral and therapeutic interventions that are within the scope of churches stewardships. We found that not only were the clergy of churches serving minorities open to such collaboration, they were anxious for partnerships that respected their theological boundaries. Rather than attempting to impose approaches that are contrary to church values, interventions need further development that will allow for enhancing the impact of efforts that are deemed to be appropriate.The primary limitations of this study include being geographically constrained and having a relatively small sample that may lack generalizeability. However, the primary intent of this study was an initial effort to explore the openness of religious clergy to engage in collaborative efforts related to HIV/AIDS. This work merely provides a glimpse of the potential to combine the influence of religious organizations with evidence-based approaches typically reserved for non-religious efforts targeting HIV/AIDS.HIV/AIDS prevention and care for the infected are seen as falling within the scope of religious organizations. Further, openness to expanding efforts in this regard was shared by clergy participating in this study. Critical next steps include more research to better understand the perspective of religious organizations and development of approaches that can be implemented within the context of their philosophical frameworks. Approaching religious leaders with tailored approaches that respect the values and practices of their particular religions will be more effective than attempting to impose approaches that do not achieve this standard. There was clear consensus among respondents that supportive partnerships rather than directive efforts are desired for increasing the effectiveness of HIV/AIDS related efforts.