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  • purchase Amyloid Beta-Peptide (1-40) will be remembered as a

    2019-04-15

    2013 will be remembered as an exceptional year in shaping our strategy to control HIV/AIDS. Indeed, a few weeks after the 30th anniversary of the discovery of the virus, a decisive step was made in deciding how to use antiretroviral therapy (ART) for treatment and prevention worldwide. New WHO public health guidelines recommended that ART should be started in all adults who reach a threshold of 500 CD4 purchase Amyloid Beta-Peptide (1-40) per μL. These guidelines were based on a strict review process and on the grounds of clinical and epidemiological benefits. Yet their application at country level remains challenging and operational guidance is needed now the target population has expanded to almost 30 million people living with HIV. Statistical modelling was very useful in the decision-making process that led to the 2013 WHO guidelines, complementing and putting into perspective the imperfect observational ART data. Furthermore, the constitution of an international network of experts who assembled and compared most available models considerably strengthened the approach. The conclusions reached were thus less debatable and the consensus achieved by this panel served the formulation of recommendations well, as in the early days of prevention of mother-to-child transmission of HIV. Recent modelling work concluded that the cost-effectiveness ratio of early ART in serodiscordant couples is very good. The HIV Modelling Consortium moves the debate several steps further with today\'s report in . By applying the best cost-benefit and cost-effectiveness methods to four distinct scenarios of generalised (South Africa, Zambia) and concentrated (Vietnam, India) epidemics, and considering high or moderate ART coverage at baseline, the Consortium provides a very powerful message: enforcing the 2013 WHO ART eligibility criteria and increasing uptake are both very cost-effective strategies according to international standards. Additionally, moving towards treatment for all adults living with HIV (or preferably all members of specific populations in concentrated epidemics) is an excellent long-term investment, competing extremely well with other high-priority health interventions. These conclusions were obtained in all scenarios combining high ART thresholds and increased uptake and with most models (the South African context, for instance, was explored with seven different models and two different strategies). The incremental effectiveness ratios varied substantially from model to model but were always well below the corresponding country\'s per capita gross domestic product. In some situations, the current guidelines and ART coverage status quo were clearly dominated—ie, improved health outcomes were achieved with the new strategies while reducing costs. Of note, the benefits increased over time, although the highest-impact interventions were not cost-saving over the 20-year horizon. The authors acknowledge that some of their assumptions could be revisited should new data become available, but the reader should be easily convinced that their conclusions are robust. Having addressed the “What if?” question, the next question is clearly “How should increasing ART thresholds and uptake be achieved?” This operational research challenge should be investigated without further delay. It is fortunate that the next 2–3 years will see direct estimates from randomised controlled trials of severe morbidity and mortality reduction in relation to early ART. Furthermore, the population acceptability and feasibility of universal test and treat introduced within combination prevention programmes will be documented in generalised epidemics. Clinicians, public health programme specialists, and national and international decision makers now have much clearer evidence for enlarging as rapidly as possible the ART eligibility criteria, taking all actions to increase coverage, and starting to plan for universal testing and treatment of those living with HIV. The priority remains to reach those most in need first, but there is also a clear urgency for short-term plans to achieve the overall target. The HIV Modelling Consortium has chosen to use a 2-year scaling-up period in their modelling exercise, which is probably overoptimistic in many settings. It should not exceed 5 years, though, or the anticipated benefits will be lesser and the overall costs higher.