title: Economic and epidemiological impact of early antiretroviral therapy initiation in India.
abstract: BACKGROUND
  Recent WHO guidance advocates for early antiretroviral therapy (ART) initiation at higher CD4 counts to improve survival and reduce HIV transmission. We sought to quantify how the cost-effectiveness and epidemiological impact of early ART strategies in India are affected by attrition throughout the HIV care continuum.
  
  
  METHODS
  We constructed a dynamic compartmental model replicating HIV transmission, disease progression and health system engagement among Indian adults. Our model of the Indian HIV epidemic compared implementation of early ART initiation (i.e. initiation above CD4 ≥350 cells/mm(3)) with delayed initiation at CD4 ≤350 cells/mm(3); primary outcomes were incident cases, deaths, quality-adjusted-life-years (QALYs) and costs over 20 years. We assessed how costs and effects of early ART initiation were impacted by suboptimal engagement at each stage in the HIV care continuum.
  
  
  RESULTS
  Assuming "idealistic" engagement in HIV care, early ART initiation is highly cost-effective ($442/QALY-gained) compared to delayed initiation at CD4 ≤350 cells/mm(3) and could reduce new HIV infections to <15,000 per year within 20 years. However, when accounting for realistic gaps in care, early ART initiation loses nearly half of potential epidemiological benefits and is less cost-effective ($530/QALY-gained). We project 1,285,000 new HIV infections and 973,000 AIDS-related deaths with deferred ART initiation with current levels of care-engagement in India. Early ART initiation in this continuum resulted in 1,050,000 new HIV infections and 883,000 AIDS-related deaths, or 18% and 9% reductions (respectively), compared to current guidelines. Strengthening HIV screening increases benefits of earlier treatment modestly (1,001,000 new infections; 22% reduction), while improving retention in care has a larger modulatory impact (676,000 new infections; 47% reduction).
  
  
  CONCLUSIONS
  Early ART initiation is highly cost-effective in India but only has modest epidemiological benefits at current levels of care-engagement. Improved retention in care is needed to realize the full potential of earlier treatment.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Manoj V
authors.initials: MV
authors.lastname: Maddali
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Dowdy
authors.affiliation: Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.|Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Amita
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; mshah28@jhmi.edu.
authors.forename: Maunank
authors.initials: M
authors.lastname: Shah
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D015658:HIV Infections / Q000517:prevention & control*; D017048:Health Care Costs; D006801:Humans; D007194:India; D019057:Quality-Adjusted Life Years
chemical_list: D019380:Anti-HIV Agents
keywords: HIV; India; antiretroviral therapy; continuum of care; cost-effectiveness