World Health Organization Demand for ARV medicines in low and middle income countries will exceed 16 million person-years by the end of 2016 V. Habiyambere, J. Perriëns, B. Dongmo-Nguimfack, World Health Organization On behalf of the ARV Forecasting Technical Working Group UNAIDS, CHAI, UNICEF, Global Fund, PEPFAR (SCMS, USAID), and Futures Institute Thank you Mr Chairman – When we submitted this abstract we gave it a bit of a headline title – a bit bold – yet: we mean it. I work for the world health organization, but the work I'm presenting today is the fruit of a collaboration with UNAIDS, CHAI, UNICEF, the Global Fund, PEPFAR, and the Futures Institute. They collaborate with us in the ARV forecasting technical working group - and have done so for the last 6 years. We are grateful for their continuing collaboration. Background: In 2013, the global capacity to supply tenofovir and efavirenz has come under strain. To ensure that enough ARVs are produced globally, WHO convened a global ARV Forecasting Technical Working Group, with UNAIDS, CHAI, UNICEF, Global Fund, PEPFAR, and Futures Institute to develop annual 3-year forecasts of the demand of ARVs since 2005. The forecasts for 2013 to the end of 2016 are presented. Methods: Forecast based on 1) annual WHO survey on ARV use, 2) volume of individual ARVs in the global procurement reporting mechanism, 3) CHAI projections for 22 high volume countries, 4) Global Fund and PEPFAR/SCMS quantification data, and 5) projected evolution of ART needs from UNAIDS and the Futures Institute. Three forecast scenarios were used and averaged arithmetically to generate the projected demand. Forecasts were broken down by active ingredient and adults vs. children. Results: Demand of ART will increase from 11.5 million (M) person-years (PYR) by end 2013 to 15.0 M by end 2015 and 16.8 M by end 2016. By 2016, the projected demand will be 15.7 M PYR of adult and 1.1 M PYR of paediatric formulation. Demand for paediatric ART will continue well beyond. The market share of tenofovir will increase from 50% in 2013 to reach 62% in 2016, that of AZT will decrease from 40% to 34 % and that of d4T will decrease from 8% to 2%. That of EFV will increase from 48% in 2013 to 63%, and NVP will gradually lose market share. Second line ART uptake will increase slowly from 4.4% now to 5.0% in 2016. Insufficient amounts of data were available to project the uptake of third line drugs. Conclusions: Scale up of ART will reach 15 M by 2015 and continue beyond. Meeting demand is a challenge, which requires reliable forecasts of future ARV demand which WHO and its technical partners will continue to produce.

WHY ? ART demand increases year by year production capacity needs to keep pace with demand Global supply security is an issue 2013: TDF and EFV 2014: d4T/3TC pediatric formulation outage; ZDV Manufacturers need independent assessment of what and how much to produce 2-3 years ahead of time We started our collaboration because ART demand increases year by year, and we wanted to be sure that production capacity needs to keep pace with demand. Global supply security is an issue In 2013 we had a supply crush for TDF and EFV This year 2014 we have a global supply outage for d4T/3TC pediatric formulation and a ZDV supply crush To be able to supply the right ARVs on time, manufacturers need independent assessment of what and how much to produce 2-3 years ahead of time, certainly when they need to bring new formulations to the market.

Methods – forecast of total future demand 3-year linear projection of ARV use in annual Global AIDS reporting Limited to 80% of total number of people needing treatment, from UNAIDS/Futures Institute, according to WHO 2013 criteria Arithmetic average 3-year extrapolation of country targets stated in annual WHO survey 3-year linear extrapolation 22 country quantifications by CHAI This slide shows how we derived the forecast of global ARV demand: We made a linear extrapolation of the number of people on treatment from the UNAIDS Global Aids Reporting, from treatment targets which countries communicated to us in an annual survey, and from quantifications by CHAI in 22 countries. To cover countries for which we had no data we extrapolated the trends per region. We limited the number treated in each country to 80% of those eligible for treatment using WHO 2013 criteria. And we then made an arythmetic average of the 3 extrapolations to generate point estimates of the number of people treated in future years. Finally we stratified our estimates by adults and children. Stratification: adult/paediatric ARV use

Total future demand This is what this looks like. In blue the observed scale up – beyond are our forecasts – and I`ll zoom into those next.

Total future demand The forecast of 16.8 million people on treatment at the end of 2016 is the average of the 18.5 from the country targets, the 16.1 of the number treated from UNAIDS/WHO global AIDS ereporting, and the 15.7 from the Clinton Foundation estimates. The average estimate for end of 2013 was 11.5 – when in reality 11.7 were reached. In the 6 years in which we produced our forecasts we have consistently underestimated the future treatment uptake be about 2%. We therefore believe that the 15 by 15 target will be met, and think that it will in fact be exceeded.

Forecast of adult/paediatric and first/second line treatment (country targets) This slide shows you how this breaks down into adult and pediatric treatment, and between first and second line treatment. First note that over the forecasting horizon we see little movement in the uptake of second line treatment – stuck at about 5% on average. Access to VL to diagnose treatment failure might change it, but its roll out is still to timid to bring about a landslide in treatment use. Second, in spite of the increasing uptake of PMTCT interventions, the number of children on treatment is not decreasing in the near future as infected children will continue to joint the pool of treated children. Over a longer time horizon there will likely be a decrease.

Methods – forecasts of market share Annual WHO survey – 16 countries reporting in each year since 2010 Arithmetic Average Global Price Reporting Mechanism – 75% of LMIC procurement lagged 1 year CHAI 21 country 5-year projections PEPFAR 2-3 year quantification - 15 countries Global Fund quantification – 54 countries in 2014 and 30 in 2015 We then proceded to forecast the market share of individual ARVs. The data considered for this are the Annual WHO survey, the WHO global price reporting mechanism (which records around 75% of all RV sales to LMIC), the CHAI projections, and quantifications by PEPFAR and the Global Fund. The share of each molecule in those databases is determined, and averaged.

Share of d4T in adult treatment How this works is illustrated on this slide - which shows the decreasing uptake of d4T. Of note is that all sources indicate the same trend – but that d4T is not expected to disappear totally: some will still be used when people cannot tolerate other ARVs.

Share of ZDV, TDF, d4T in adult treatment This shows the average of the trends predicted for ZDV, TDF and d4T - with TDF going up, and ZDV going down – perhaps a but slower than expected.

Share of EFV, NVP, LPV and ATV in adult treatment Here is the predicted market share of NNRTI and PI's in adult treatment – EFV replacing NVP, and ATV nibbling at the market share of LPV.

Limitations and next steps Overlap between data sets Limited time horizon No insight on formulation use New molecules not included We will expand time horizon to 5 – 7 years Will drill down to formulation level

But the bottom line is: We are on track for 15 million by 2015 New drugs are being introduced and older ones are disappearing Without significant impact on the cost of ART in LMIC More on access to ARV drugs (price, regulatory status, API, forecast of use, issues in MIC) on: http://www.who.int/hiv/amds/en/