Abstract #: WEAD0203 Estimating the size of the pediatric ARV market in 27 low- and middle-income countries (LMICs) through 2025 as PMTCT initiatives continue to succeed Vineet R. Prabhu, Shaun McGovern, Paul Domanico PRESENTED AT THE 9TH IAS CONFERENCE ON HIV SCIENCE - PARIS, FRANCE

Conflict of Interest No conflicts of interest to declare

The paradox we face in addressing pediatric HIV Ensure best pediatric ARV formulations available End pediatric HIV Directional sense of evolution of CLHIV population needed to understand future need for formulations and commercial considerations

Pediatric ARV market much smaller than adult market 2015 Figures for “generic accessible” LMICs Unlike the adult market, new infections are dropping significantly with PMTCT, and older children are “ageing out” Note: “Generic-accessible” denotes countries where global generic manufacturers can register and supply a large proportion of that country’s ARV volume needs Source: CHAI ARV Market Report, 2016

“Super Fast-Track Targets” aim to reduce the number of children living with HIV/AIDS (CLHIV) even further START FREE Eliminate new HIV infections among children by reducing the number of children newly infected to less than 40,000 by 2018 and 20,000 by 2020. STAY FREE Ensure counselling and prevention services for adolescents etc. AIDS FREE Provide 1.6 million children (0-14 years) and 1.2 million adolescents (15-19) living with HIV with antiretroviral therapy by 2018. Provide 1.4 million children (0-14) and 1 million adolescents (15-19) with HIV treatment by 2020 Even if not met on schedule, these ambitious targets will have a strong (positive) effect on the pediatric population living with HIV

Several challenges in estimating the pediatric population in need of various new ARV formulations Lack of reliable data! Age and weight band distributions in country Line of therapy breakdown Regimen breakdown Formulation breakdown Others….

Global Figures (2016 estimates)* Thinking about the overall size of CLHIV population as it inevitably declines… Global Figures (2016 estimates)* 2011 2012 2013 2014 2015 Total PLHIV; Children ages 0-14 2,100,000 2,000,000 1,900,000 1,800,000 New Infections; Children age 0-14 270,000 230,000 200,000 160,000 150,000 YoY % drop in new infections   -15% -13% -20% -6% AIDS-related deaths; Children age 0-14 170,000 140,000 120,000 110,000 -12% -7% -14% -8% *2017 estimates are slightly higher but directionally similar As new infections (+) and deaths (-) decrease, “ageing out” will be a major factor in the decline of this population Source: UNAIDS AIDSInfo Database, accessed March 2017; revised estimates became available July 2017

Modelling the population by tracking age cohorts New Infections (decreasing) 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 Age 0 Age 1 Age 2 Age 3 Age 4 Age 5 Age 6 Age 7 Age 8 Age 9 Age 10 Age 11 Age 12 Age 13 Age 14 Mortality (decreasing) “Aging out”

Provisional age-specific breakdown for estimated CLHIV (2011-2015) were provided by UNAIDS for 27 high-volume countries 27 Countries Benin Lesotho Swaziland Botswana Liberia Togo Burkina Faso Malawi Uganda Burundi Mozambique United Republic of Tanzania Cambodia Myanmar Cameroon Nigeria Viet Nam Côte d’Ivoire Papua New Guinea Zambia Ethiopia Rwanda Zimbabwe Kenya Senegal Lao PDR South Africa In 2015, these 27 countries represented 77% of global CLHIV burden, and 85% within LMICs Note: The estimates provided by UNAIDS are modelled and provisional. The data do have limitations in accuracy especially at the individual country level.

Assumptions used 27 country Age 0 cohort; 2015 64,075 Per UNAIDS provisional estimates Super fast-track targets for “Start Free” met? (scenarios for decline in age 0 cohort) On time (aggressive) 2 yrs late (moderate) Status quo (conservative) Annual ped. new infections drop per “Status Quo” (i.e. if Start Free targets not met) 8% (2011-2015 CAGR was -14%; 2014-2015 was -10%) Ped. (age 0-14) mortality (global); 2015 110,000 Per UNAIDS 27 country contribution to global ped. mortality; 2015 77% (84,700) Total CLHIV in 26 countries was 77% of global, 85% of GA LMICs in 2015) Annual ped. mortality drop (2011-2015 CAGR was -10%; 2014-2015 was -8%) Note: For modelling purposes, the 20,000 new infections of the “Start Free” targets are attributed entirely to the 27 countries even though the targets are global Total projected mortality assumed to be equally distributed across the age groups each year

Scenarios lead to different implied new infection rates Implied new infections and mortality for 27 countries with assumptions used Number of Children Note: For modelling purposes, the 20,000 new infections of the “Start Free” targets are attributed entirely to the 27 countries even though the targets are global Total projected mortality assumed to be equally distributed across the age groups each year

Scenarios suggest between 350-500K CLHIV by 2025 in 27 high burden LMICs Pediatric population (ages 0-14) living with HIV in 27 high-burden LMICs CLHIV ages 0-14 (‘000s) (Status Quo) (“Stay Free” met by 2022) (“Stay Free” met by 2020)

Weight band distribution of CLHIV (ages 0-14) in 27 high-burden LMICs by scenario: skewing heavier (a) Aggressive scenario (b) Moderate scenario (c) Conservative scenario Note: Age to weight conversions as per Doherty K et al. (2014) BMC Health Serv Res. 14:201

Limitations Analysis based on 2015 figures; revised UNAIDS estimates are now available suggesting higher number of CLHIV than previously thought Country level estimates provided by UNAIDS are modelled and provisional; limitations in accuracy Model simplifies new infections by attributing only to age 0 cohort; transmission through breast feeding may occur at older ages Overestimates younger age and lower weight bands in outer years Model simplifies annual mortality by distributing evenly across ages 1-14 Current distribution by age is not well known

Conclusions Overall number of CLHIV (age 0-14) will decline as PMTCT efforts continue to succeed CLHIV population will increasingly skew towards older and heavier children, especially as ART coverage increases and mortality declines Variance in scenarios of overall population may be greater than variance likely with different ART coverage, 2L migration, or market share scenarios Demand for pediatric formulations for the lowest weight bands will likely reduce over time Careful consideration will need to be given to post-regulatory commercial sustainability of newer desired pediatric formulations Innovative financing mechanisms may be needed These estimates are not meant to be definitive, but do provide a frame of reference

Acknowledgements Mary Mahy (UNAIDS) CHAI colleagues Funders