Test and treat all as soon as possible
Authors: François Dabis
Journal: The Lancet Global Health (2013)

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 cells per μL.1WHOConsolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach.http://www.who.int/hiv/pub/guidelines/arv2013/en/index.htmlGoogle Scholar 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.2Doherty M Ford N Vitoria M Weiler G Hirnschall G The 2013 WHO guidelines for antiretroviral therapy: evidence-based recommendations to face new epidemic realities.Curr Opin HIV AIDS. 2013; 8: 528-534Crossref PubMed Scopus (53) Google Scholar 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.3The HIV Modeling Consortium Treatment as Prevention Editorial Writing GroupHIV treatment as prevention: models, data and questions—towards evidence-based decision-making.PLoS Med. 2012; 9: e1001259Crossref PubMed Scopus (68) Google Scholar 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.4Dabis F Newell ML Fransen L et al.Prevention of mother-to-child transmission of HIV in developing countries: recommendations for practice.Health Policy Plann. 2000; 15: 34-42Crossref PubMed Scopus (45) Google Scholar Recent modelling work5Walensky RP Ross EL Kumarasamy N et al.Cost-effectiveness of HIV treatment as prevention in serodiscordant couples.N Engl J Med. 2013; 369: 1715-1725Crossref PubMed Scopus (104) Google Scholar 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 The Lancet Global Health.6Eaton JW Menzies NA Stover J et al.How should HIV programmes respond to evidence for the benefits of earlier treatment initiation? A combined analysis of twelve mathematical models.Lancet Glob Health. 2013; (published online Dec 10.)http://dx.doi.org/10.1016/S2214-109X(13)70172-4Google Scholar 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.7US National Institutes of HealthStrategic timing of antiretroviral treatment (START).http://clinicaltrials.gov/ct2/show/NCT00867048Google Scholar, 8French National Agency for Research on AIDS and Viral HepatitisEarly antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults (ANRS 12136 TEMPRANO).http://clinicaltrials.gov/ct2/show/NCT00495651Google Scholar Furthermore, the population acceptability and feasibility of universal test and treat introduced within combination prevention programmes will be documented in generalised epidemics.9Vermund SH Fidler SH Ayles H Beyers N Hayes RJ Can combination prevention strategies reduce HIV transmission in generalized epidemic settings in Africa? The HPTN 071 (PopART) study plan in South Africa and Zambia.J Acquir Immune Defic Syndr. 2013; 63: S221-S227Crossref PubMed Scopus (37) Google Scholar, 10Iwuji CC Orne-Gliemann J Tanser F et al.Evaluation of the impact of immediate versus WHO recommendations-guided antiretroviral therapy initiation on HIV incidence: the ANRS 12249 TasP (Treatment as Prevention) trial in Hlabisa sub-district, KwaZulu-Natal, South Africa: study protocol for a cluster randomised controlled trial.Trials. 2013; 14: 230Crossref PubMed Scopus (91) Google Scholar 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,1WHOConsolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach.http://www.who.int/hiv/pub/guidelines/arv2013/en/index.htmlGoogle Scholar 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,6Eaton JW Menzies NA Stover J et al.How should HIV programmes respond to evidence for the benefits of earlier treatment initiation? A combined analysis of twelve mathematical models.Lancet Glob Health. 2013; (published online Dec 10.)http://dx.doi.org/10.1016/S2214-109X(13)70172-4Google Scholar 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. Paying now rather than forever has never been as relevant as a global health solution to the HIV pandemic than in 2013. The relative success of the ongoing replenishment session for the Global Fund11The Global Fund to fight AIDSTuberculosis and MalariaGlobal Fund donors pledge US$12 billion.http://www.theglobalfund.org/en/mediacenter/newsreleases/2013-12-03_Global_Fund_Donors_Pledge_USD_12_Billion/Google Scholar is a positive signal, although still insufficient considering the evidence-based targets that are set for the coming years. Finally, it is probably time to change the meaning of the acronym TasP, which currently stands for treatment as prevention. It is too restrictive to reflect our evolving thinking around the use of ART. To be in line with the available evidence, an alternative slogan for 2014 onwards could be: Test and treat All as Soon as Possible (TASP). I declare that I have no conflicts of interest. Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical modelsOur estimates suggest that earlier eligibility for antiretroviral therapy is very cost effective in low-income and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets. Full-Text PDF Open Access