When to start antiretroviral therapy in resource-limited settings

Rochelle P. Walensky, Lindsey L. Wolf, Robin Wood, Mariam O. Fofana, Kenneth A. Freedberg, Neil A. Martinson, A. David Paltiel, Xavier Anglaret, Milton C. Weinstein, Elena Losina

Research output: Contribution to journalArticlepeer-review


Background: The results of international clinical trials that are assessing when to initiate antiretroviral therapy (ART) will not be available for several years. Objective: To inform HIV treatment decisions about the optimal CD4 threshold at which to initiate ART in South Africa while awaiting the results of these trials. Design: Cost-effectiveness analysis by using a computer simulation model of HIV disease. Data Sources: Published data from randomized trials and observational cohorts in South Africa. Target Population: HIV-infected patients in South Africa. Time Horizon: 5-year and lifetime. Perspective: Modified societal. Intervention: No treatment, ART initiated at a CD4 count less than 0.250 × 109 cells/L, and ART initiated at a CD4 count less than 0.350 × 109 cells/L. Outcome Measures: Morbidity, mortality, life expectancy, medical costs, and cost-effectiveness. Results of Base-Case Analysis: If 10% to 100% of HIV-infected patients are identified and linked to care, a CD4 count threshold for ART initiation of 0.350 × 109 cells/L would reduce severe opportunistic diseases by 22 000 to 221 000 and deaths by 25 000 to 253 000 during the next 5 years compared with ART initiation at 0.250 × 109 cells/L; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART initiation strategy would increase long-term survival by at least 7.9 years, with a mean per-person life expectancy of 3.8 years with no ART and 12.5 years with an initiation threshold of 0.350 × 109 cells/L. Compared with an initiation threshold of 0.250 × 109 cells/L, a threshold of 0.350 × 109 cells/L has an incremental cost-effectiveness ratio of $1200 per year of life saved. Results of Sensitivity Analysis: Initiating ART at a CD4 count less than 0.350 × 109 cells/L would remain cost-effective over the next 5 years even if the probability that the trial would demonstrate the superiority of earlier therapy is as low as 17%. Limitation: This model does not consider the possible benefits of initiating ART at a CD4 count greater than 0.350 × 10 9 cells/L or of reduced HIV transmission. Conclusion: Earlier initiation of ART in South Africa will probably reduce morbidity and mortality, improve long-term survival, and be cost-effective. While awaiting trial results, treatment guidelines should be liberalized to allow initiation at CD4 counts less than 0.350 × 109 cells/L, earlier than is currently recommended. Primary Funding Source: National Institute of Allergy and Infectious Diseases and the Doris Duke Charitable Foundation.

Original languageEnglish (US)
Pages (from-to)157-166
Number of pages10
JournalAnnals of Internal Medicine
Issue number3
StatePublished - Aug 4 2009
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine

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