When to Start Antiretroviral Therapy in Resource-Limited Settings

  1. Rochelle P. Walensky, MD, MPH;
  2. Lindsey L. Wolf, SB;
  3. Robin Wood, FCP, MMed, DTM&H;
  4. Mariam O. Fofana, AB;
  5. Kenneth A. Freedberg, MD, MSc;
  6. Neil A. Martinson, MBBCh, MPH;
  7. A. David Paltiel, PhD;
  8. Xavier Anglaret, MD, PhD;
  9. Milton C. Weinstein, PhD;
  10. Elena Losina, PhD; and
  11. for the CEPAC (Cost-Effectiveness of Preventing AIDS Complications)-International Investigators*
  1. From the 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; University of Cape Town, Cape Town, and Perinatal HIV Research Unit, Johannesburg, South Africa; Johns Hopkins University, Baltimore, Maryland; Yale School of Medicine, New Haven, Connecticut; and Université Victor Segalen Bordeaux 2, Bordeaux, France.

    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 × 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 × 109 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.

    Article and Author Information

    • Acknowledgment: The authors thank Daniel R. Kuritzkes, MD; Paul E. Sax, MD; and Bethany Morris.

    • Grant Support: By the National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476, P30 AI060354, and U01 AI068634) and the Doris Duke Charitable Foundation (Clinical Scientist Development Award).

    • Potential Financial Conflicts of Interest: None disclosed.

    • Reproducible Research Statement: The authors have provided a detailed technical appendix (Appendix 2) for this and many other CEPAC papers. This appendix describes the depth of model structure and the breadth of the input parameters; for further questions, please contact Dr. Walensky.

    • Requests for Single Reprints: Rochelle P. Walensky, MD, MPH, Division of General Medicine, Massachusetts General Hospital, 50 Staniford Street, 9th Floor, Boston, MA 02114.

    • Current Author Addresses: Drs. Walensky, Freedberg, and Losina; Ms. Wolf; and Ms. Fofana: Massachusetts General Hospital, Division of General Medicine, 50 Staniford Street, 9th Floor, Boston, MA 02114.

    • Dr. Wood: Institute of ID and Molecular Medicine, University of Cape Town Faculty of Health Sciences, Anzio Road, Observatory 7925, Cape Town, South Africa.

    • Dr. Martinson: WITS Health Consortium, 8 Blackwood Ridge, Parktown, Johannesburg, 2193 South Africa.

    • Dr. Paltiel: Yale University School of Medicine, 60 College Street, New Haven, CT 06520.

    • Dr. Anglaret: Unité Inserm 897, Université Bordeaux-2, 146 rue Léo-Saignat, 33076 Bordeaux, France.

    • Dr. Weinstein: Harvard School of Public Health, Department of Health Policy and Management, Program in Health Decision Science, 718 Huntington Avenue, Boston, MA 02115.

    • Author Contributions: Conception and design: R.P. Walensky, L.L. Wolf, R. Wood, K.A. Freedberg, A.D. Paltiel, M.C. Weinstein.

    • Analysis and interpretation of the data: R.P. Walensky, L.L. Wolf, R. Wood, M.O. Fofana, K.A. Freedberg, X. Anglaret, M.C. Weinstein, E. Losina.

    • Drafting of the article: R.P. Walensky.

    • Critical revision of the article for important intellectual content: R.P. Walensky, R. Wood, K.A. Freedberg, N.A. Martinson, A.D. Paltiel, X. Anglaret, M.C. Weinstein, E. Losina.

    • Final approval of the article: R.P. Walensky, L.L. Wolf, R. Wood, M.O. Fofana, K.A. Freedberg, N.A. Martinson, A.D. Paltiel, X. Anglaret, M.C. Weinstein, E. Losina.

    • Statistical expertise: M.C. Weinstein, E. Losina.

    • Obtaining of funding: R.P. Walensky, K.A. Freedberg.

    • Administrative, technical, or logistic support: L.L. Wolf, M.O. Fofana.

    • Collection and assembly of data: R. Wood, N.A. Martinson.

    • ↵* For a list of the CEPAC-International investigators, see Appendix 1.

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    1. Ann Intern Med August 4, 2009 vol. 151 no. 3 157-166
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