Scaling up the 2010 World Health Organization HIV Treatment Guidelines in resource-limited settings: a model-based analysis

PLoS Med. 2010 Dec 21;7(12):e1000382. doi: 10.1371/journal.pmed.1000382.


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.

Methods and findings: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy
  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / economics
  • Anti-HIV Agents / therapeutic use
  • Cost-Benefit Analysis
  • Female
  • Guidelines as Topic*
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Models, Theoretical*
  • World Health Organization*
  • Young Adult


  • Anti-HIV Agents