title: Patient- and population-level health consequences of discontinuing antiretroviral therapy in settings with inadequate HIV treatment availability.
abstract: BACKGROUND
  In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes.
  
  
  METHODS
  In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the Alternative strategy, discontinuation of second-line ART occurred upon detection of antiretroviral failure, specified by WHO guidelines. Those discontinuing failed ART experienced an increased risk of AIDS-related mortality compared to those continuing ART.
  
  
  RESULTS
  At the population level, the Alternative strategy increased the mean number initiating ART annually by 1,100 individuals (+18.7%) to 6,980 compared to the Status Quo. More individuals initiating ART under the Alternative strategy increased total life-years by 15,000 (+2.8%) to 555,000, compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for those treated decreased by 0.7 years (-8.0%) to 8.1 years compared to the Status Quo. In a cohort of treated patients only, 600 more individuals (+27.1%) died by 5 years under the Alternative strategy compared to the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and treatment capacity. Although we believe the results robust in the short-term, this analysis reflects settings where HIV case detection occurs late in the disease course and treatment capacity and the incidence of newly detected patients are stable.
  
  
  CONCLUSIONS
  In settings with inadequate HIV treatment availability, trade-offs emerge between maximizing outcomes for individual patients already on treatment and ensuring access to treatment for all people who may benefit. While individuals may derive some benefit from ART even after virologic failure, the aggregate public health benefit is maximized by providing effective therapy to the greatest number of people. These trade-offs should be explicit and transparent in antiretroviral policy decisions.
authors.affiliation: Department of Healthcare Policy and Research, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA. adkimmel@vcu.edu.
authors.forename: April D
authors.initials: AD
authors.lastname: Kimmel
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Resch
authors.forename: Xavier
authors.initials: X
authors.lastname: Anglaret
authors.forename: Norman
authors.initials: N
authors.lastname: Daniels
authors.forename: Sue J
authors.initials: SJ
authors.lastname: Goldie
authors.forename: Christine
authors.initials: C
authors.lastname: Danel
authors.forename: Angela Y
authors.initials: AY
authors.lastname: Wong
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Freedberg
authors.forename: Milton C
authors.initials: MC
authors.lastname: Weinstein