title: Scaling up the 2010 World Health Organization HIV Treatment Guidelines in resource-limited settings: a model-based analysis.
abstract: BACKGROUND
  The new 2010 World Health Organization (WHO) HIV treatment guidelines recommend earlier antiretroviral therapy (ART) initiation (CD4<350 cells/µl instead of CD4<200 cells/µl), multiple sequential ART regimens, and replacement of first-line stavudine with tenofovir. This paper considers what to do first in resource-limited settings where immediate implementation of all of the WHO recommendations is not feasible.
  
  
  RESULTS
  We use a mathematical model and local input data to project clinical and economic outcomes in a South African HIV-infected cohort (mean age = 32.8 y, mean CD4 = 375/µl). For the reference strategy, we assume that all patients initiate stavudine-based ART with WHO stage III/IV disease and receive one line of ART (stavudine/WHO/one-line). We rank-in survival, cost-effectiveness, and equity terms-all 12 possible combinations of the following: (1) stavudine replacement with tenofovir, (2) ART initiation (by WHO stage, CD4<200 cells/µl, or CD4<350 cells/µl), and (3) one or two regimens, or lines, of available ART. Projected life expectancy for the reference strategy is 99.0 mo. Considering each of the guideline components separately, 5-y survival is maximized with ART initiation at CD4<350 cells/µl (stavudine/<350/µl/one-line, 87% survival) compared with stavudine/WHO/two-lines (66%) and tenofovir/WHO/one-line (66%). The greatest life expectancies are achieved via the following stepwise programmatic additions: stavudine/<350/µl/one-line (124.3 mo), stavudine/<350/µl/two-lines (177.6 mo), and tenofovir/<350/µl/two-lines (193.6 mo). Three program combinations are economically efficient: stavudine/<350/µl/one-line (cost-effectiveness ratio, US$610/years of life saved [YLS]), tenofovir/<350/µl/one-line (US$1,140/YLS), and tenofovir/<350/µl/two-lines (US$2,370/YLS).
  
  
  CONCLUSIONS
  In settings where immediate implementation of all of the new WHO treatment guidelines is not feasible, ART initiation at CD4<350 cells/µl provides the greatest short- and long-term survival advantage and is highly cost-effective.
authors.affiliation: Division of Infectious Disease, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. rwalensky@partners.org
authors.forename: Rochelle P
authors.initials: RP
authors.lastname: Walensky
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Ciaranello
authors.forename: A David
authors.initials: AD
authors.lastname: Paltiel
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Lorenzana
authors.forename: Xavier
authors.initials: X
authors.lastname: Anglaret
authors.forename: Adam W
authors.initials: AW
authors.lastname: Stoler
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Freedberg
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D005260:Female; D017408:Guidelines as Topic; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D014944:World Health Organization; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents