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Background: Optimal resource allocation for antiretroviral treatment (ART) in developing countries requires assessment of different strategies for drug treatment and laboratory monitoring., Objectives: To compare costs and outcomes for 10 000 simulated HIV-infected patients followed every 6 months for 10 years in a limited-resource setting., Method: Five nested strategies, with and without the availability of a second-line treatment regimen, were simulated: (a) no ART (NO ART); (b) with ART but without any laboratory markers of HIV other than positive serology (ART ONLY); (c) ART plus total lymphocyte count (TLC); (d) ART plus CD4 cell counts (CD4); and (e) ART plus CD4 cell count plus viral load measurement (VL). Baseline prices of CD4 cell count and viral load measurements were $5.00 and $25.00 per test, respectively., Results: With no second-line treatment available, treating 10 000 patients with ART ONLY compared with NO ART would cost $14.49 million [95% confidence interval (CI), 14.45-14.52] and would generate an additional 23 060 quality-adjusted life years (QALYS) (95% CI, 22 770-23 360) for a median incremental cost effectiveness ratio (ICER) of $628/QALY. Median ICER values per QALY for CD4 and VL strategies are $238 and $16 139, respectively, when second-line treatment is unavailable. With second-line ART available, the corresponding median ICER values are $8636, and $14 670., Conclusions: In the absence of second-line ART, the CD4 strategy is a more cost-effective laboratory testing strategy for managing HIV infection than either TLC or VL. Availability of second-line ART plus CD4 cell count and/or viral load measurement would save additional lives, but at high incremental cost.

This paper discusses the issue of equity in the distribution of ARV drugs in the Malawi health system. Malawi is one of the countries most severely affected by HIV/AIDS in southern Africa. It is also one of the poorest countries in the world. ARV drugs are expensive.The Malawi government, with assistance from the Global Fund on Tuberculosis, Malaria and HIV/AIDS, started providing free ARV drugs to eligible HIV-infected people in September 2004. The provision of free drugs brought the hope that everyone who was eligible would access them. Based on data collected through a qualitative research methodology, it was found that achieving equity in provision would face several challenges including policy, operational and socio-economic considerations. Specifically, the existing policy framework, shortage of medical personnel, access to information and inadequacy of effective community support groups are some of the key issues affecting equity.

To date, a minority of persons living with HIV worldwide has benefited from the advances in HIV therapeutics fueled by the scientific community, policy-makers, advocates, and the pharmaceutical industry in the global North. A growing body of evidence demonstrates that access to highly active antiretroviral therapy can be successfully scaled-up in less wealthy nations in the South. High rates of adherence correspond with clinical, immunologic, and virologic outcomes similar to those seen in wealthier nations. Recent reports of successful programs highlight the provision of free care, reliance on the international funding sources, and proactive adherence counseling. As access to antiretroviral therapy has improved, there is an urgent need to develop better strategies for initiating and monitoring therapy, including the scale-up of viral load testing.

Background: Significant quantities of antiretroviral drugs (ARVs) to treat HIV/AIDS have been procured for Sub-Saharan Africa for the first time in their 20-year history. This presents a novel opportunity to empirically study the roles of brand and generic suppliers in providing access to ARVs., Methodology/principal Findings: An observational study of brand and generic supply based on a dataset of 2,162 orders of AIDS drugs for Sub-Saharan Africa reported to the Global Price Reporting Mechanism at the World Health Organization from January 2004-March 2006 was performed. Generic companies supplied 63% of the drugs studied, at prices that were on average about a third of the prices charged by brand companies. 96% of the procurement was of first line drugs, which were provided mostly by generic firms, while the remaining 4%, of second line drugs, was sourced primarily from brand companies. 85% of the generic drugs in the sample were manufactured in India, where the majority of the drugs procured were ineligible for patent protection. The remaining 15% was manufactured in South Africa, mostly under voluntary licenses provided by brand companies to a single generic company. In Sub-Saharan African countries, four first line drugs in the dataset were widely patented, however no general deterrent to generic purchasing based on a patent was detected., Conclusions/significance: Generic and brand companies have played distinct roles in increasing the availability of ARVs in Sub-Saharan Africa. Generic companies provided most of the drugs studied, at prices below those charged by brand companies, and until now, almost exclusively supplied several fixed-dose combination drugs. Brand companies have supplied almost all second line drugs, signed voluntary licenses with generic companies, and are not strictly enforcing patents in certain countries. Further investigation into how price reductions in second line drugs can be achieved and the cheapest drugs can actually be procured is warranted.

Objectives: This study analyses the effect of the Andean countries' June 2003 negotiation of antiretroviral drug (ARV) prices. The objectives were to assess the problems faced during the negotiation process, to evaluate the impact of the negotiation on ARV prices, and to identify factors that could make it difficult for countries to implement the results of the negotiation., Methods: Price information of ARVs purchased by public programmes during 2004 was collected from the ministries of health. A survey of the ministries of health was conducted using a questionnaire with information related to the countries' health care and drug regulations and policies. Interviews with a convenient sample of key Andean health authorities and other stakeholders were also conducted., Results: Study results show that the negotiation did achieve lower prices and higher quality and bioequivalence standards for ARVs. However, in general, the public health care programmes of the six countries analysed did not purchase ARVs from the companies that participated in the negotiation, nor did they base purchases on the prices or quality and bioequivalence criteria established in the negotiation. Prices paid by the Andean countries' public programmes in 2004 were a weighted average of 65% higher than the negotiated prices; and this difference in negotiated prices vs. actual prices represented 39.5% of the programmes' ARV expenditures in 2004, or US$18 million in ARV expenditures., Conclusion: The successful development and implementation of multinational price negotiations requires that participant countries coordinate pharmaceutical regulations and policies, and pool procurement processes.

HIV/AIDS care has benefited tremendously from the availability of antiretroviral (ARV) drugs, both branded and generic. Drug discovery and innovation is the result of direct investment in the development of branded medications, a crucial process for future improvements in care. However, the cost of branded medications is too high for resource-limited countries, where most persons with HIV/AIDS live. Generic drugs dramatically lower the cost of care; however, their safety and efficacy must be ensured and maintained. Proven bioavailability and bioequivalence, in addition to satisfactory manufacturing, distribution, and administration, are keys to successfully implementing the use of qualified generic ARVs. Agencies such as the US Food and Drug Administration (FDA), European Medicines Agency (EMEA), and the World Health Organization (WHO), continue to strengthen the surveillance process through which qualified generic and branded drugs are provided worldwide. Generic drugs have the potential to cause harm if rigorous standards for their use are not followed, but those that are qualified offer great promise in the treatment of HIV/AIDS.

Background: No more than 8% of HIV positive children needing treatment in low- and middle-income countries have access to antiretroviral drugs (ARVs). Children presently account for about 4% of all treated patients, while for equitable access they should make up at least 13%., Aims: This study explores key issues, implications and interaction dynamics to boost production of easy-to-use and affordable fixed-dose combination (FDC) ARVs for children in the developing world. Potentials for equitable solutions are examined including priority steps and actions, appropriate treatment options and reliable forecasting methods for paediatric ARVs, as well as combination incentives to generic companies against market unattractiveness and enforced intellectual property (IP) rights. Moreover, implementation strategies to enhance the development and production of affordable ARV paediatric formulations and appropriate supply systems to ensure availability are investigated., Results: The current market for FDC paediatric ARVs is already substantial and will only grow with improved and scaled up diagnosis and monitoring of children. This provides an argument for immediate increase of production and development of FDC ARVs for children. These formulations must be low cost and included in the list of Essential Medicines to avoid children continuing to lag behind in access to treatment. Access-oriented, long-term drug policy strategies with the ability to pass muster of governments, the UN system, as well as generic and research-based enterprises are needed to let children gain expanded and sustained access to FDC ARVs. Under the requirements listed above, IP-bound Voluntary License (VL) flexibilities do appear, if coupled with substantial combination incentives to generic firms, as a fitting tool into the needs. Policies must consider enhancing human resource capacity in the area of caregivers and social and health workers aiming to spread correct information and awareness on effectiveness and rationale of FDC ARVs for children. Policies should urge that paediatric ARV treatment programmes entwine with extant interventions on prevention of mother-to-child transmission, as well as with HIV treatment initiatives focused on mothers and household members. Policies, again, should consider centralising functions and pooling resources to help overcome drug supply barriers. WHO's brokering role in VL-based agreements between wealthy and developing country industries, as well as its technical guidance in setting international standards should not be waived while looking for sustained access to optimised ARV treatments for children. Strategies discussed in this paper, while taking unavoidability of marketing and profit rules into account, look closely into the trade and drug policy directions of China and India according to frontier crossing implications of their IP management trends as well as their multi-faceted penetration strategies of both the wealthy and under-served markets the world over.

Problem: Many resource-poor countries have started scaling up antiretroviral therapy (ART). While reports from individual clinics point to successful implementation, there is limited information about progress in government institutions at a national level., Approach: Malawi started national ART scale-up in 2004 using a structured approach. There is a focus on one generic, fixed-dose combination treatment with stavudine, lamivudine and nevirapine. Treatment is delivered free of charge to eligible patients with HIV and there is a standardized system for recruiting patients, monthly follow-up, registration, monitoring and reporting of cases and outcomes. All treatment sites receive quarterly supervision and evaluation., Local Setting: In January 2004, there were nine public sector facilities delivering ART to an estimated 4 000 patients. By December 2005, there were 60 public sector facilities providing free ART to 37,840 patients using national standardized systems. Analysis of quarterly cohort treatment outcomes at 12 months showed 80% of patients were alive, 10% dead, 9% lost to follow-up and 1% had stopped treatment., Lessons Learned: Achievements were the result of clear national ART guidelines, implementing partners working together, an intensive training schedule focused on clinical officers and nurses, a structured system of accrediting facilities for ART delivery, quarterly supervision and monitoring, and no stock-outs of antiretroviral drugs. The main challenges are to increase the numbers of children, pregnant women and patients with tuberculosis being started on ART, and to avert high early mortality and losses to follow-up. The capacity of the health sector to cope with escalating case loads and to scale up prevention alongside treatment will determine the future success of ART delivery in Malawi.

Problem: Drug procurement and distribution practices are weak in many resource-poor countries, and are a major reason for lack of access to medicines. With many countries scaling up antiretroviral therapy (ART), it is vital to avoid interrupted drug supplies, which would lead to drug resistance and treatment failure., Approach: Malawi has adapted a model, based on that adopted by the country's Tuberculosis Control Programme, to allow rational ART drug forecasting., Local Setting: The model includes a focus on one standardized first-line ART regimen; a "push system" and "ceilings" for first-line ART drugs for facilities; use of starter pack and continuation pack kits; quarterly monitoring of patient outcomes and ART drug stocks at facility level; provision of a three-month buffer stock of ART drugs at facility level; and use of a procurement and distribution system outside central medical stores., Lessons Learned: The focus on a single first-line regimen, "ceilings" for first-line ART drugs and quarterly data collections to calculate drug needs (for new and follow-up patients, respectively), as well as the use of an independent procurement facility, allow drug orders to be made 6-9 months ahead. These measures have so far ensured that there have been no ART drug stock-outs in the country.

Many countries with financial support for HIV treatment experience delays in scale-up because of bureaucratic, operational, and technical obstacles. The authors describe the Peruvian National HIV Program's response to such challenges. A team of consultants experienced in the scale-up of the Peruvian national program to treat multidrug-resistant tuberculosis worked with the national HIV program to identify and address key factors contributing to slow enrollment of HIV patients into the antiretroviral treatment program. The rate of enrollment into the antiretroviral treatment program increased from 124 patients/month in the first 9 months of the program to 226 patients/month in the last 7 months, an increase of 83%. This strategy achieved 38.5% coverage of the population in need. Effective programmatic expansion of the Peruvian National HIV Program was facilitated by a multidisciplinary collaboration in a systematized effort to overcome barriers to scale-up.

Purpose: The April 2005 Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents recommended 9 regimens to be combined with 2 nucleoside reverse transcriptase inhibitors (NRTIs). These regimens are effective in lowering viral load but are expensive. This study aimed to determine the cost for each regimen to achieve an undetectable viral load., Method: 52 clinical trials were reviewed. The outcome measure was cost per undetectable patient, C/PU, where C = cost of a drug, and PU = percent of patients with undetectable viral loads., Results: For 30 weeks, cost per undetectable (<400 copies/mL) ranged from 4,416 dollars (efavirenz) to 23,110 dollars (nelfinavir); for 42 weeks, the range was 5,729 dollars (efavirenz) to 24,071 dollars (indinavir/ritonavir); for 60 weeks, it ranged from 9,535 dollars (efavirenz) to 26,829 dollars (fosamprenavir); and for 84 weeks, it ranged from 12,203 dollars (efavirenz) to 22,960 dollars (nelfinavir). For <50 copies/mL, at 30 weeks the range was from 7,140 dollars (efavirenz) to 17,548 dollars (atazanavir); for 42 weeks, it ranged from 9,849 dollars (lopinavir/ritonavir) to 13,181 dollars (nelfinavir); for 60 weeks, it ranged from 8,702 dollars (nevirapine) to 36,034 dollars (atazanavir); and for 84 weeks, it ranged from 15,660 dollars (efavirenz) to 29,177 dollars (indinavir/ritonavir)., Conclusion: Efavirenz's low price and high effectiveness make it the least expensive means of achieving an undetectable viral load.

Objective: We sought to project the lifetime cost of medical care for human immunodefiency virus (HIV)-infected adults using current antiretroviral therapy (ART) standards., Methods: Medical visits and hospitalizations for any reason were from the HIV Research Network, a consortium of high-volume HIV primary care sites. HIV treatment drug regimen efficacies were from clinical guidelines and published sources; data on other drugs used were not available. In a computer simulation model, we projected HIV medical care costs in 2004 U.S. dollars., Results: From the time of entering HIV care, per person projected life expectancy is 24.2 years, discounted lifetime cost is Dollars 385,200, and undiscounted cost is Dollars 618,900 for adults who initiate ART with CD4 cell count < 350/microL. Seventy-three percent of the cost is antiretroviral medications, 13% inpatient care, 9% outpatient care, and 5% other HIV-related medications and laboratory costs. For patients who initiate ART with CD4 cell count < 200/microL, projected life expectancy is 22.5 years, discounted lifetime cost is Dollars 354,100 and undiscounted cost is Dollars 567,000. Results are sensitive to drug manufacturers' discounts, ART efficacy, and use of enfuvirtide for salvage. If costs are discounted to the time of infection, the discounted lifetime cost is Dollars 303,100., Conclusions: Effective ART regimens have substantially improved survival and have increased the lifetime cost of HIV-related medical care in the U.S.

Objectives: To (a) determine early treatment outcomes and (b) assess safety in children treated with adult fixed-dose combination (FDC) antiretroviral tablets., Setting: Sixteen Medecins Sans Frontieres (MSF) HIV programs in eight countries in resource-limited settings (RLS)., Methods: Analysis of routine program data gathered June 2001 to March 2005., Results: A total of 1184 children [median age, 7 years; inter-quartile range (IQR), 4.6-9.3] were treated with antiretroviral therapy (ART) of whom 616(52%) were male. At ART initiation, Centres for Disease Control stages N, A, B and C were 9, 14, 38 and 39%, respectively. Children were followed up for a median period of 6 months (IQR, 2-12 months). At 12 months the median CD4 percentage gain in children aged 18-59 months was 15% (IQR, 6-18%), and the percentage with CD4 gain < 15% was reduced from 85% at baseline to 11%. In those aged 60-156 months, median CD4 cell count gain was 275 cells/microl (IQR, 84-518 cells/microl), and the percentage with CD4 < 200 cells/mul reduced from 51% at baseline to 11%. Treatment outcomes included; 1012 (85%) alive and on ART, 36 (3%) deaths, 15 (1%) stopped ART, 89 (8%) lost to follow-up, and 31 (3%) with unknown outcomes. Overall probability of survival at 12 months was 0.87 (0.84-0.89). Side effects caused a change to alternative antiretroviral drugs in 26 (2%) but no deaths., Conclusions: Very satisfactory early outcomes can be achieved in children in RLS using generic adult FDC antiretroviral tablets. These findings strongly favour their use as an "interim solution" for scaling-up ART in children; however, more appropriate pediatric antiretroviral drugs remain urgently needed.

Background: As antiretroviral therapy is increasingly used in settings with limited resources, key questions about the timing of treatment and use of diagnostic tests to guide clinical decisions must be addressed., Methods: We assessed the cost-effectiveness of treatment strategies for a cohort of adults in Côte d'Ivoire who were infected with the human immunodeficiency virus (HIV) (mean age, 33 years; CD4 cell count, 331 per cubic millimeter; HIV RNA level, 5.3 log copies per milliliter). Using a computer-based simulation model that incorporates the CD4 cell count and HIV RNA level as predictors of disease progression, we compared the long-term clinical and economic outcomes associated with no treatment, trimethoprim-sulfamethoxazole prophylaxis alone, antiretroviral therapy alone, and prophylaxis with antiretroviral therapy., Results: Undiscounted gains in life expectancy ranged from 10.7 months with antiretroviral therapy and prophylaxis initiated on the basis of clinical criteria to 45.9 months with antiretroviral therapy and prophylaxis initiated on the basis of CD4 testing and clinical criteria, as compared with trimethoprim-sulfamethoxazole prophylaxis alone. The incremental cost per year of life gained was 240 dollars (in 2002 U.S. dollars) for prophylaxis alone, 620 dollars for antiretroviral therapy and prophylaxis without CD4 testing, and 1,180 dollars for antiretroviral therapy and prophylaxis with CD4 testing, each compared with the next least expensive strategy. None of the strategies that used antiretroviral therapy alone were as cost-effective as those that also used trimethoprim-sulfamethoxazole prophylaxis. Life expectancy was increased by 30% with use of a second line of antiretroviral therapy after failure of the first-line regimen., Conclusions: A strategy of trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy, with the use of clinical criteria alone or in combination with CD4 testing to guide the timing of treatment, is an economically attractive health investment in settings with limited resources., (Copyright 2006 Massachusetts Medical Society.)

Background: In October 2001, a paying antiretroviral therapy service was introduced at a Central Hospital in Malawi using stavudine 40 mg/lamivudine 150 mg/nevirapine 200 mg (triomune). The objective of this study was to determine characteristics of patients seeking antiretroviral therapy, retention in care, clinical outcomes, and outlines for program improvement., Methods: Retrospectively, all patients seeking anti-retroviral therapy initiation (October 2001 to October 2002; follow-up through April 2003) were evaluated for laboratory results, retention in care, toxicity, and mortality. Hazard ratios for factors associated with dropout were determined., Results: Of 757 patients seeking evaluation, 625 began treatment. Documented mortality rate was 61 of 757. Total dropout rate was 50%. Factors associated with dropout include CD4 count <50 cells/mm(3) and Kaposi's sarcoma. Twenty-seven of 625 patients discontinued therapy for toxicity., Conclusions: The paying antiretroviral therapy program showed an unacceptable dropout rate associated with advanced baseline disease. Severe toxicity rate was low. Areas for improved program performance include lower cost, wide and earlier access to antiretroviral therapy, and targeted retention strategies.

Objectives: To present direct manufacturing costs and price calculations of individual antiretroviral drugs, enabling those responsible for their procurement to have a better understanding of the cost structure of their production, and to indicate the prices at which these antiretroviral drugs could be offered in developing country markets., Methods: Direct manufacturing costs and factory prices for selected first and second-line antiretroviral drugs were calculated based on cost structure data from a state-owned company in Brazil. Prices for the active pharmaceutical ingredients (API) were taken from a recent survey by the World Health Organization (WHO). The calculated prices for antiretroviral drugs are compared with quoted prices offered by privately-owned, for-profit manufacturers., Results: The API represents the largest component of direct manufacturing costs (55-99%), while other inputs, such as salaries, equipment costs, and scale of production, have a minimal impact. The calculated prices for most of the antiretroviral drugs studied fall within the lower quartile of the range of quoted prices in developing country markets. The exceptions are those drugs, primarily for second-line therapy, for which the API is either under patent, in short supply, or in limited use in developing countries (e.g. abacavir, lopinavir/ritonavir, nelfinavir, saquinavir)., Conclusion: The availability of data on the cost of antiretroviral drug production and calculation of factory prices under a sustainable business model provide benchmarks that bulk purchasers of antiretroviral drugs could use to negotiate lower prices. While truly significant price decreases for antiretroviral drugs will depend largely on the future evolution of API prices, the present study demonstrates that for several antiretroviral drugs price reduction is currently possible. Whether or not these reductions materialize will depend on the magnitude of indirect cost and profit added by each supplier over the direct production costs. The ability to achieve price reductions in line with production costs will have critical implications for sustainable treatment for HIV/AIDS in the developing world.

With the advent of highly active antiretroviral therapy (HAART), the prognosis for HIV-infected individuals with access has been transformed. HAART provides one of the most cost-effective treatments for any chronic disease. Immediate cost remains a legitimate factor when choosing HAART regimens, however, the cost of long-term side-effects and adherence issues must also be considered. The review examines the cost issues associated with HAART prescription and its influence on prescribing policies.

Background: As widespread adoption of potent combination antiretroviral therapy (ART) reaches its tenth year, our objective was to quantify the cumulative survival benefits of acquired immunodeficiency syndrome (AIDS) care in the United States., Methods: We defined eras corresponding to advances in standards of human immunodeficiency virus (HIV) disease care, including opportunistic infection prophylaxis, treatment with ART, and the prevention of mother-to-child transmission (pMTCT) of HIV. Per-person survival benefits for each era were determined using a mathematical simulation model. Published estimates provided the number of adult patients with new diagnoses of AIDS who were receiving care in the United States from 1989 to 2003., Results: Compared with survival associated with untreated HIV disease, per-person survival increased 0.26 years with Pneumocystis jiroveci pneumonia prophylaxis alone. Four eras of increasingly effective ART in addition to prophylaxis resulted in per-person survival increases of 7.81, 11.05, 11.57, and 13.33 years, compared with the absence of treatment. Treatment for patients with AIDS in care in the United States since 1989 yielded a total survival benefit of 2.8 million years. pMTCT averted nearly 2900 infant infections, equivalent to 137,000 additional years of survival benefit., Conclusions: At least 3.0 million years of life have been saved in the United States as a direct result of care of patients with AIDS, highlighting the significant advances made in HIV disease treatment.

A large number of HIV-infected patients in sub-Saharan Africa pay out-of-pocket for HAART. This analysis from Botswana indicates that higher median out-of-pocket regimen costs to patients for the initial 30 days of HAART are associated with failure to achieve a viral load< 400 copies/ml [US$32; interquartile range (IQR), 20-84 compared with US$22; (IQR, 17-36), P = 0.001]. HAART costs should be minimized as scale-up efforts in sub-Saharan Africa progress.

The prevalence of adult HIV/AIDS in Thailand is declining due to intense prevention strategies, but it still continues to be a critical health problem with a prevalence of 1.5%. Several HIV vaccine candidates for the prevention of HIV infection or progress to AIDS were examined in clinical trials. We evaluated the cost-effectiveness of a vaccination regimen (rBCG prime-rDIs boost) currently in its pre-clinical phase. The cost-effectiveness of three interventions (vaccination, highly active antiretroviral treatment [HAART], and the combination of the two) through an existing vaccination program was assessed in a Markov model. The disability-adjusted life year (DALY) was the main effectiveness measure. In the base case the efficacy of the vaccine for preventing HIV infection was assumed to be 30%. The cost of the vaccine was estimated on the basis of its predicted production capacities in Thailand. The incremental cost-effectiveness ratios of vaccination, HAART, and the combination were about dollar US 75, dollar US 610, and dollar US 267 per DALY averted compared with the do-nothing strategy in the base case. The HAART-only strategy seemed to be less cost-effective than the other options under the current assumptions. Sensitivity analyses indicated that the new HIV infection rate and the vaccine efficacy could affect the results.

A patient with respiratory failure due to undiagnosed tuberculosis in the presence of HIV infection presents to the ICU in a foreign country. This raises many ethical questions, quite apart from the medical management issues raised by the patient's serious condition. Six of these ethical questions have been presented to leading physicians and an ethicist, from a range of national, cultural and religious backgrounds, for their comment.

The Purchase price report released in August 2004 by the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund) was the first publication of a significant amount of real transaction purchase data for antiretrovirals (ARVs). We did an observational study of the ARV transaction data in the Purchase price report to examine the procurement behaviour of principal recipients of Global Fund grants in developing countries. We found that, with a few exceptions for specific products (e.g. lamivudine) and regions (e.g. eastern Europe), prices in low-income countries were broadly consistent or lower than the lowest differential prices quoted by the research and development sector of the pharmaceutical industry. In lower middle-income countries, prices were more varied and in several instances (lopinavir/ritonavir, didanosine, and zidovudine/lamivudine) were very high compared with the per capita income of the country. In all low- and lower middle-income countries, ARV prices were still significantly high given limited local purchasing power and economic strength, thus reaffirming the need for donor support to achieve rapid scale-up of antiretroviral therapy. However, the price of ARVs will have to decrease to render scale-up financially sustainable for donors and eventually for governments themselves. An important first step in reducing prices will be to make available in the public domain as much ARV transaction data as possible to provide a factual basis for discussions on pricing. The price of ARVs has considerable implications for the sustainability of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) treatment in the developing world.

Cost-effectiveness analysis (CEA) compares the costs and outcomes of two or more technologies. However, there is no consensus about which measure of effectiveness should be used in each analysis. Clinical researchers have to select an appropriate outcome for their purpose, and this choice can have dramatic consequences on the conclusions of their analysis. In this paper we present a Bayesian cost-effectiveness framework to carry out CEA when more than one measure is considered. In particular, we analyse the case in which two measures of effectiveness, one binary and the other continuous, are considered. Decision-making measures, such as the incremental cost-effectiveness ratio, incremental net-benefit and cost-effectiveness acceptability curves, are used to compare costs and one measure of outcome. We propose an extension of cost-acceptability curves, namely the cost-effectiveness acceptability plane, as a suitable measure for decision taking. The models were validated using data from two clinical trials. In the first one, we compared four highly active antiretroviral treatments applied to asymptomatic HIV patients. As measures of effectiveness, we considered the percentage of patients with undetectable levels of viral load, and changes in quality of life, measured according to EuroQol. In the second clinical trial we compared three methadone maintenance programmes for opioid-addicted patients. In this case, the measures of effectiveness considered were quality of life, according to the Nottingham Health Profile, and adherence to the treatment, measured as the percentage of patients who participated in the whole treatment programme., (Copyright 2006 John Wiley & Sons, Ltd.)

Background: The anticipated scale-up of antiretroviral therapy (ART) in high-prevalence, resource-constrained settings requires operational research to guide policy on the design of treatment programmes. Mathematical models can explore the potential impacts of various treatment strategies, including timing of treatment initiation and provision of laboratory monitoring facilities, to complement evidence from pilot programmes., Methods and Findings: A deterministic model of HIV transmission incorporating ART and stratifying infection progression into stages was constructed. The impact of ART was evaluated for various scenarios and treatment strategies, with different levels of coverage, patient eligibility, and other parameter values. These strategies included the provision of laboratory facilities that perform CD4 counts and viral load testing, and the timing of the stage of infection at which treatment is initiated. In our analysis, unlimited ART provision initiated at late-stage infection (AIDS) increased prevalence of HIV infection. The effect of additionally treating pre-AIDS patients depended on the behaviour change of treated patients. Different coverage levels for ART do not affect benefits such as life-years gained per person-year of treatment and have minimal effect on infections averted when treating AIDS patients only. Scaling up treatment of pre-AIDS patients resulted in more infections being averted per person-year of treatment, but the absolute number of infections averted remained small. As coverage increased in the models, the emergence and risk of spread of drug resistance increased. Withdrawal of failing treatment (clinical resurgence of symptoms), immunologic (CD4 count decline), or virologic failure (viral rebound) increased the number of infected individuals who could benefit from ART, but effectiveness per person is compromised. Only withdrawal at a very early stage of treatment failure, soon after viral rebound, would have a substantial impact on emergence of drug resistance., Conclusions: Our analysis found that ART cannot be seen as a direct transmission prevention measure, regardless of the degree of coverage. Counselling of patients to promote safe sexual practices is essential and must aim to effect long-term change. The chief aims of an ART programme, such as maximised number of patients treated or optimised treatment per patient, will determine which treatment strategy is most effective.

As HIV/AIDS drugs are becoming more widely available in Southern Africa, we compared the effectiveness and cost effectiveness of different treatment options, using a Markov Monte Carlo simulation model based on published estimates of disease progression, treatment effectiveness and health care costs. Cost and outcome values were discounted. Quality of life was considered. Acceptability curves summarized uncertainties. Sensitivity analyses tested assumptions. Results showed that triple antiretroviral therapy (ARV) plus antibiotics would prolong life by 6.7 undiscounted years if provided 'late' (CD4 = 200 cells/microl) and by 9.8 years if provided 'early' (CD4 = 350 cells/microl). The incremental undiscounted costs per year of life gained, compared to no preventive therapy, were $17 for isoniazid plus cotrimoxazole started late, $244 for both antibiotics started early, $2454 for ARV plus antibiotics started late and $2784 for ARV plus both antibiotics started early. The discounted incremental costs per quality adjusted life year (QALY) gained were, respectively, $29 saving, $254, $4937 and $3057. Late ARV plus both antibiotics was the strategy most likely to be cost effective if society was willing to pay more than $2000 per life year gained. Cost-effectiveness estimates were sensitive to discounting and assumed treatment costs but were less sensitive to assumed treatment effectiveness.

The diffusion of protease inhibitors and non-nucleoside reverse transcriptase inhibitors in the US in 1996 and 1997 reduced the number of deaths attributable to HIV disease and changed the way we think about the illness. Today, HIV disease may be deemed a fairly expensive chronic condition rather than an intolerably expensive fatal illness. Although most studies have found that patients receiving new drug therapies are hospitalised less frequently than patients who received early drug therapies, it is unclear whether the diffusion of new drug therapies has increased or decreased the annual cost of care. However, it is evident that the diffusion of new drug therapies has increased the lifetime cost of care. Analysts rely on models to simulate the course and cost of HIV disease. This study reviews the evolution of these models, paying particular attention to how these models estimate the cost of care. The primary findings of this review are that the economic data used in these models are often too imprecise to accurately identify the cost of each disease stage and are almost always outdated. Moreover, it was found that estimates of drug costs in these models may not accurately reflect actual expenditures.

Malawi offers antiretroviral treatment (ART) to all HIV-positive adults who are clinically classified as being in WHO clinical stage III or IV without 'universal' CD4 testing. This study was conducted among such adults attending a rural district hospital HIV/AIDS clinic (a) to determine the proportion who have CD4 counts >or=350 cells/microl, (b) to identify risk factors associated with such CD4 counts and (c) to assess the validity and predictive values of possible clinical markers for CD4 counts >or=350 cells/microl. A CD4 count >or=350 cells/microl was found in 36 (9%) of 401 individuals who are thus at risk of being placed prematurely on ART. A body mass index (BMI) >22 kg/m(2), the absence of an active WHO indicator disease at the time of presentation for ART, and a total lymphocyte count >1,200 cells/microl were significantly associated with such a CD4 count. The first two of these variables could serve as clinical markers for selecting subgroups of patients who should undergo CD4 testing. In a resource-limited district setting, assessing the BMI and checking for active opportunistic infections are routine clinical procedures that could be used to target CD4 measurements, thereby minimising unnecessary CD4 measurements, unnecessary (too early) treatment and costs.

Objectives: We evaluated the cost-effectiveness of fee-based and free testing strategies at an HIV voluntary counseling and testing (VCT) program integrated into a community-based AIDS service organization in Moshi, Tanzania., Methods: We waived the usual fee schedule during a 2-week free, advertised VCT campaign; analyzed the number of clients testing per day during prefree, free, and postfree testing periods; and estimated the cost-effectiveness of limited and sustained free testing strategies., Results: The number of clients testing per day increased from 4.1 during the prefree testing interval to 15.0 during the free testing campaign (P<.0001) and remained significantly increased at 7.1 (P<.0001) after resumption of the standard fees. HIV seroprevalence (16.7%) and risk behaviors were unchanged over these intervals. Modeled over 1 year, the costs per infection averted with the standard fee schedule, with a 2-week free VCT campaign, and with sustained free VCT year-round were $170, $105, and $92, respectively, and the costs per disability-adjusted life year gained were $8.72, $5.40, and $4.72, respectively., Conclusions: The provision of free VCT enhances both the number of clients testing per day and its cost-effectiveness in resource-limited settings.

The paper traces Brazil's efforts to fight AIDS in the last 20 years. The analysis concentrates on the efforts to combat and prevent the deadly infectious disease through ingenious efforts of private citizens, government agencies, national and international NGOs, which challenged multinational companies, international organizations and foreign governments. While the investigation led to a positive evaluation of the joint efforts in managing the threat, it is made clear that the fight against the HIV/AIDS virus is far from over in Brazil and will have to be strengthened on the local, national and international level.

Introduction: A lack of treatment compliance, resistances and non-advanced stages of the disease are the reasons why not all HIV-infected patients benefit from the demonstrated efficacy of antiretroviral drug combinations--with the consequent important increase in costs. A prospective cohort follow-up study is conducted to analyze the distribution of antiretroviral pharmaceutical expenditure in a district hospital, and the possibilities for improving its efficiency., Material and Methods: The study comprised 128 HIV-infected patients seen for 12 consecutive weeks (September to November, 2004). The characteristics of previous follow-up were analyzed, and the patients were divided into groups according to the course over the following weeks and the results of prescribed treatment: group 1 (effective treatment), group 2 (ineffective treatment), and group 3 (treatment dropout). Based on the prescription history, corroborated with drug retrieval and the acquisition costs (FARMASYS software), the cost of antiretroviral medication was calculated for each of the 108 patients receiving highly active antiretroviral therapy (HAART). The statistical analysis was carried out with the SPSS version 11.5 statistical package, and considering statistical significance for p < 0.05., Results: The cost generated by the 108 patients included during the study period who received HAART was 232,366 euros, with an average of 2,151 euros per patient and 19,363 euros per day of consultation. The distribution of patients and of the costs generated by the above defined groups was as follows: group 1: 79 patients (80.6%); group 2: 11 patients (10.6%); group 3: 18 patients (8.8%). In the group 1 patients, 15.2% of the antiretroviral expenditure corresponded to patients who had started therapy with a CD4+ count of > 350 cells/ml, while 45% had > 350 cells/ml at the present time, and 25.9% had > 500 cells/ml. Previous medication dropout was identified as a predictor of new dropouts and treatment failures., Comment: While the cost generated by antiretroviral medication is high, 19.4% is administered to patients who do not benefit from such treatment due to a lack of efficacy or dropouts, and in another 40-60% of cases the need for such treatment could be subject to consideration in view of the good immune status of the patients.

To build the knowledge base on anti-retroviral (ARV) treatment compliance in Africa, a study has been carried out at Yaoundé University Hospital. It documented and studied the follow up of 231 patients under tri-therapy at the time of the study (December 2003). Respecting the strict time schedules is a crucial issue, especially for taking the morning and evening doses of medication. This is true for all patients, regardless of their social or economic status. The majority of the patients request more thorough information about their treatment. Some patients face economic problems which are more often related to the indirect costs rather than to the cost of treatment. Finally, the difficulty in confronting the treatment's side effects or the galenic nature of ARV treatment itself is noted. Nevertheless, it seems that the patients could better manage these issues and deal with the ensuing challenges if better communication with more complete information was provided to them at the beginning of their treatment, accompanied by written fact sheets specific to each type of treatment.