title: When to start antiretroviral therapy in resource-limited settings.
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.
  
  
  METHODS
  Cost-effectiveness analysis by using a computer simulation model of HIV disease.
  
  
  METHODS
  Published data from randomized trials and observational cohorts in South Africa.
  
  
  METHODS
  HIV-infected patients in South Africa.
  
  
  METHODS
  5-year and lifetime.
  
  
  CONCLUSIONS
  Modified societal.
  
  
  METHODS
  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.
  
  
  METHODS
  Morbidity, mortality, life expectancy, medical costs, and cost-effectiveness.
  
  
  RESULTS
  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
  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%.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  National Institute of Allergy and Infectious Diseases and the Doris Duke Charitable Foundation.
authors.affiliation: Massachusetts General Hospital, Brigham and Women's Hospital, Harvard University Medical School, Harvard School of Public Health, and Boston University School of Public Health, Boston, Massachusetts 02114, USA.
authors.forename: Rochelle P
authors.initials: RP
authors.lastname: Walensky
authors.forename: Lindsey L
authors.initials: LL
authors.lastname: Wolf
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Mariam O
authors.initials: MO
authors.lastname: Fofana
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Freedberg
authors.forename: Neil A
authors.initials: NA
authors.lastname: Martinson
authors.forename: A David
authors.initials: AD
authors.lastname: Paltiel
authors.forename: Xavier
authors.initials: X
authors.lastname: Anglaret
authors.forename: Milton C
authors.initials: MC
authors.lastname: Weinstein
authors.forename: Elena
authors.initials: E
authors.lastname: Losina
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000191:economics / Q000517:prevention & control*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000191:economics*; D000890:Anti-Infective Agents / Q000008:administration & dosage; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003198:Computer Simulation; D003362:Cost-Benefit Analysis; D003663:Decision Trees; D018450:Disease Progression; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy* / Q000191:economics / Q000401:mortality; D017048:Health Care Costs; D006801:Humans; D008017:Life Expectancy; D012680:Sensitivity and Specificity; D013019:South Africa; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage
chemical_list: D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination