When to start antiretroviral therapy in resource-limited settings

Ann Intern Med. 2009 Aug 4;151(3):157-66. doi: 10.7326/0003-4819-151-3-200908040-00138. Epub 2009 Jul 20.

Abstract

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 x 10(9) cells/L, and ART initiated at a CD4 count less than 0.350 x 10(9) 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 x 10(9) 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 x 10(9) 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 x 10(9) cells/L. Compared with an initiation threshold of 0.250 x 10(9) cells/L, a threshold of 0.350 x 10(9) 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 x 10(9) 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 x 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 x 10(9) cells/L, earlier than is currently recommended.

Primary funding source: National Institute of Allergy and Infectious Diseases and the Doris Duke Charitable Foundation.

Publication types

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

MeSH terms

  • AIDS-Related Opportunistic Infections / economics
  • AIDS-Related Opportunistic Infections / prevention & control*
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / economics*
  • Anti-Infective Agents / administration & dosage
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Computer Simulation
  • Cost-Benefit Analysis
  • Decision Trees
  • Disease Progression
  • Drug Administration Schedule
  • HIV Infections / drug therapy*
  • HIV Infections / economics
  • HIV Infections / mortality
  • Health Care Costs
  • Humans
  • Life Expectancy
  • Sensitivity and Specificity
  • South Africa
  • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage

Substances

  • Anti-HIV Agents
  • Anti-Infective Agents
  • Trimethoprim, Sulfamethoxazole Drug Combination