Scaling Up the 2010 World Health Organization HIV Treatment Guidelines in Resource-Limited Settings: A Model-Based Analysis

Background: The new 2010 World Health Organization (WHO) HIV treatment guidelines recommend earlier antiretroviral therapy (ART) initiation (CD4<350 cells/mu l instead of CD4<200 cells/mu l), 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/mu l). 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/mu l, or CD4,350 cells/mu l), 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/mu l (stavudine/<350/mu l/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/mu l/one-line (124.3 mo), stavudine/<350/mu l/two-lines (177.6 mo), and tenofovir/<350/mu l/two-lines (193.6 mo). Three program combinations are economically efficient: stavudine/<350/ml/one-line (cost-effectiveness ratio, US$610/years of life saved [YLS]), tenofovir/<350/mu l/one-line (US$1,140/YLS), and tenofovir/<350/mu l/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/mu ml provides the greatest short-and long-term survival advantage and is highly cost-effective.