Jeffrey W Eaton1, Nicolas A Menzies2, John Stover3, Valentina Cambiano4, Leonid Chindelevitch5, Anne Cori6, Jan A C Hontelez7, Salal Humair5, Cliff C Kerr8, Daniel J Klein9, Sharmistha Mishra10, Kate M Mitchell11, Brooke E Nichols12, Peter Vickerman11, Roel Bakker13, Till Bärnighausen14, Anna Bershteyn9, David E Bloom5, Marie-Claude Boily1, Stewart T Chang9, Ted Cohen15, Peter J Dodd16, Christophe Fraser6, Chaitra Gopalappa3, Jens Lundgren17, Natasha K Martin18, Evelinn Mikkelsen19, Elisa Mountain1, Quang D Pham8, Michael Pickles1, Andrew Phillips4, Lucy Platt11, Carel Pretorius3, Holly J Prudden11, Joshua A Salomon20, David A M C van de Vijver12, Sake J de Vlas13, Bradley G Wagner9, Richard G White16, David P Wilson8, Lei Zhang8, John Blandford21, Gesine Meyer-Rath22, Michelle Remme11, Paul Revill23, Nalinee Sangrujee21, Fern Terris-Prestholt11, Meg Doherty24, Nathan Shaffer24, Philippa J Easterbrook24, Gottfried Hirnschall24, Timothy B Hallett25. 1. Department of Infectious Disease Epidemiology, Imperial College London, London, UK. 2. Center for Health Decision Science, Harvard School of Public Health, Boston, MA, USA. 3. Futures Institute, Glastonbury, CT, USA. 4. Research Department of Infection and Population Health, University College London, London, UK. 5. Department of Global Health and Population, Harvard School of Public Health, Boston, MA, USA. 6. MRC Centre for Outbreak Analysis and Modelling, Imperial College London, London, UK. 7. Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands; Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Mtubatuba, South Africa; Nijmegen International Center for Health System Analysis and Education (NICHE), Department of Primary and Community Care, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. 8. Kirby Institute, University of New South Wales, Sydney, Australia. 9. Institute for Disease Modelling, Intellectual Ventures Laboratory, Bellevue, WA, USA. 10. Department of Infectious Disease Epidemiology, Imperial College London, London, UK; Division of Infectious Diseases, St Michael's Hospital, University of Toronto, Toronto, ON, Canada. 11. Social and Mathematical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK. 12. Department of Virology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands. 13. Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands. 14. Department of Global Health and Population, Harvard School of Public Health, Boston, MA, USA; Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Mtubatuba, South Africa. 15. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Division of Global Health Equity, Brigham and Women's Hospital, Boston, MA, USA. 16. Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK. 17. Centre for Viral Diseases, Department of Infectious Diseases, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark; Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. 18. Social and Mathematical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK; School of Social and Community Medicine, University of Bristol, Bristol, UK. 19. Nijmegen International Center for Health System Analysis and Education (NICHE), Department of Primary and Community Care, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. 20. Center for Health Decision Science, Harvard School of Public Health, Boston, MA, USA; Department of Global Health and Population, Harvard School of Public Health, Boston, MA, USA. 21. Division of Global HIV/AIDS, US Centers for Disease Control and Prevention, Atlanta, GA, USA. 22. Center for Global Health and Development, Boston University, Boston, MA, USA; Health Economics and Epidemiology Research Office, Department of Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa. 23. Centre for Health Economics, University of York, York, UK. 24. Department of HIV/AIDS, WHO, Geneva, Switzerland. 25. Department of Infectious Disease Epidemiology, Imperial College London, London, UK. Electronic address: timothy.hallett@imperial.ac.uk.
Abstract
BACKGROUND: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. METHODS: We used several independent mathematical models in four settings-South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP. FINDINGS: In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from $237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to $749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost effective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to $241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost effective. INTERPRETATION: Our 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. FUNDING: Bill & Melinda Gates Foundation, WHO.
BACKGROUND: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. METHODS: We used several independent mathematical models in four settings-South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP. FINDINGS: In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from $237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to $749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost effective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to $241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost effective. INTERPRETATION: Our 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. FUNDING: Bill & Melinda Gates Foundation, WHO.
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