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/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/mu;l/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;l provides the greatest short- and long-term survival advantage and is highly cost-effective. © 2010 Walensky et al.