Among individuals retained on ART, virological suppression rates during the first 5 years of ART were high (>80%) and stable. Suppression rates in ITT analysis declined during 4 years.

The Brazilian HIV/AIDS drug policy has been highly debated and even criticized, particularly at the time of its implementation by the Government in early 90s. However, after more than a decade of action, the success of the Brazilian response to HIV is evident and recognized worldwide, lying upon a concerted early governmental response, a strong and effective participation of the civil society, a multisectoral mobilization, a balanced prevention and treatment approach and the advocacy of human rights in all strategies, particularly with the policy of wide access to antiretroviral drugs. This policy made highly active anti-retroviral therapy (HAART) universally available since 1996, with logistic and criteria distribution based on regularly updated national guidelines. Approximately 140,000 patients now receive antiretroviral (ARV) treatment through the public health system. As a result there has been a significant fall in morbidity/mortality rates, hospital admissions and costs of treatment, with significant growth in demand for outpatient services and decrease for hospital, home and day-care services. It has also led to improvements in the quality of life for HIV+ individuals and savings in the medical costs, while economic and social related costs also have fallen. The policy of universal access to combined antiretroviral treatment (ART)' in Brazil has been shown to be cost-effective and the financial resources devoted to this initiative represents an economically viable investment. This experience also shows that a well-designed and supported international effort to reduce drug prices and improve health infrastructure could overcome many obstacles in middle-income and limited-resource countries.

Summary Background With continued roll-out of antiretroviral therapy (ART) in resource-limited settings, evidence is emerging of increasing levels of transmitted drug-resistant HIV. We aimed to compare the effectiveness and cost-effectiveness of different potential public health responses to substantial levels of transmitted drug resistance. Methods We created a model of HIV transmission, progression, and the effects of ART, which accounted for resistance generation, transmission, and disappearance of resistance from majority virus in the absence of drug pressure. We simulated 5000 ART programmatic scenarios with different prevalence levels of detectable resistance in people starting ART in 2017 (t0) who had not previously been exposed to antiretroviral drugs. We used the model to predict cost-effectiveness of various potential changes in policy triggered by different prevalence levels of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) measured in the population starting ART. Findings Individual-level resistance testing before ART initiation was not generally a cost-effective option, irrespective of the cost-effectiveness threshold. At a cost-effectiveness threshold of US$500 per quality-adjusted life-year (QALY), no change in policy was cost effective (ie, no change in policy would involve paying less than $500 per QALY gained), irrespective of the prevalence of pretreatment NNRTI resistance, because of the increased cost of the policy alternatives. At thresholds of $1000 or higher, and with the prevalence of pretreatment NNRTI resistance greater than 10%, a policy to measure viral load 6 months after ART initiation became cost effective. The policy option to change the standard first-line treatment to a boosted protease inhibitor regimen became cost effective at a prevalence of NNRTI resistance higher than 15%, for cost-effectiveness thresholds greater than $2000. Interpretation Cost-effectiveness of potential policies to adopt in response to different levels of pretreatment HIV drug resistance depends on competing budgetary claims, reflected in the cost-effectiveness threshold. Results from our model will help inform WHO recommendations on monitoring of HIV drug resistance in people starting ART. Funding WHO (with funds provided by the Bill & Melinda Gates Foundation), CHAIN (European Commission).

Despite the exponential growth in the literature on modelling and simulation studies of impact and cost-effectiveness in different aspects of healthcare, there is no clear consensus on the appropriate role of modelling in the development of recommendations in clinical guidelines. This is compounded both by the lack of a standardised approach to assess the quality of modelling, and lack of clarity on its positioning within the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method for decision-making in the development of WHO guidelines, that considers both evidence from systematic reviews of randomized clinical trials (RTCs) or observational studies, together with stakeholder values and preferences, resource use, and feasibility issues. In the development of the 2013 WHO Consolidated Guidelines on the use of Antiretroviral drugs for treating and preventing HIV infection, a series of modelling projects were undertaken to inform the recommendations on eligibility criteria for ART initiation, and approaches to monitoring for treatment response. We report our experiences, challenges encountered, and several key considerations to guide the future use of modelling in the development of WHO guidelines. These are: (1) Transparency in the conduct and reporting of model inputs and results; (2) The need for agreed standards for critical appraisal and use of modelling data in healthcare policy making; (3) recognition that modelling of cost-effectiveness is only one component of decision-making in development of WHO recommendations and in priority-setting; (4) The need for closer interaction and an ongoing dialogue between modellers and model end-users or decision-makers; (5) the important role of WHO in convening and facilitating comparative assessment of multiple models; and (6) The need to optimize research and data collection to inform modelling studies.