Influence of Alternative Thresholds for Initiating HIV Treatment on Quality-Adjusted Life Expectancy: A Decision Model

  1. R. Scott Braithwaite, MD, MSc;
  2. Mark S. Roberts, MD, MPP;
  3. Chung Chou H. Chang, PhD;
  4. Matthew Bidwell Goetz, MD;
  5. Cynthia L. Gibert, MD, MSc;
  6. Maria C. Rodriguez-Barradas, MD;
  7. Steven Shechter, PhD;
  8. Andrew Schaefer, PhD;
  9. Kimberly Nucifora, MS;
  10. Robert Koppenhaver, MS; and
  11. Amy C. Justice, MD, PhD
  1. From Yale University and Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California; George Washington University and Veterans Affairs Medical Center, Washington, D.C.; Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; and University of British Columbia, Vancouver, British Columbia, Canada.

    Abstract

    Background: The optimal threshold for initiating HIV treatment is unclear.

    Objective: To compare different thresholds for initiating HIV treatment.

    Design: A validated computer simulation was used to weigh important harms from earlier initiation of antiretroviral therapy (toxicity, side effects, and resistance accumulation) against important benefits (decreased HIV-related mortality).

    Data Sources: Veterans Aging Cohort Study (5742 HIV-infected patients and 11 484 matched uninfected controls) and published reports.

    Target Population: Individuals with newly diagnosed chronic HIV infection and varying viral loads (10 000, 30 000, 100 000, and 300 000 copies/mL) and ages (30, 40, and 50 years).

    Time Horizon: Unlimited.

    Perspective: Societal.

    Intervention: Alternative thresholds for initiating antiretroviral therapy (CD4 counts of 200, 350, and 500 cells/mm3).

    Outcome Measures: Life-years and quality-adjusted life-years (QALYs).

    Results of Base-Case Analysis: Although the simulation was biased against earlier treatment initiation because it used an upper-bound assumption for therapy-related toxicity, earlier treatment increased life expectancy and QALYs at age 30 years regardless of viral load (life expectancies with CD4 initiation thresholds of 500, 350, and 200 cells/mm3 were 18.2 years, 17.6 years, and 17.2 years, respectively, for a viral load of 10 000 copies/mL and 17.3 years, 15.9 years, and 14.5 years, respectively, for a viral load of 300 000 copies/mL), and increased life expectancies at age 40 years if viral loads were greater than 30 000 copies/mL (life expectancies were 12.5 years, 12.0 years, and 11.4 years, respectively, for a viral load of 300 000 copies/mL).

    Results of Sensitivity Analysis: Findings favoring early treatment were generally robust.

    Limitations: Results favoring later treatment may not be valid. The findings may not be generalizable to women.

    Conclusion: This simulation suggests that earlier initiation of combination antiretroviral therapy is often favored compared with current recommendations.

    Article and Author Information

    • Grant Support: By the National Institute of Alcohol Abuse and Alcoholism (grants K23 AA14483-01, 2U10 AA13566).

    • Potential Financial Conflicts of Interest:Consultancies: M.S. Roberts (Archimedes). Grants received: M.S. Roberts (National Institutes of Health).

    • Requests for Single Reprints: R. Scott Braithwaite, MD, MSc, Yale University, 950 Campbell Avenue, West Haven, CT 06516; e-mail, Ronald.Braithwaite{at}va.gov.

    • Current Author Addresses: Drs. Braithwaite and Justice and Ms. Nucifora: Yale University, 950 Campbell Avenue, West Haven, CT 06516.

    • Drs. Roberts and Chang: University of Pittsburgh, 200 Meyran Avenue, Pittsburgh, PA 15213.

    • Dr. Goetz: Veterans Affairs Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, Los Angeles, CA 90073.

    • Dr. Gilbert: Veterans Affairs Medical Center, 50 Irving Street NW, Washington, DC 20422.

    • Dr. Rodriguez-Barradas: Veterans Affairs Medical Center, 2002 Holcombe Boulevard, Houston, TX 77030.

    • Dr. Shechter: University of British Columbia, 2053 Main Mall, Vancouver, British Columbia V6T172, Canada.

    • Dr. Schaefer: University of Pittsburgh, 3800 Ottawa Street, Pittsburgh, PA 15261.

    • Mr. Koppenhaver: University of Pittsburgh, 1048 Benedum Hall, Pittsburgh, PA 15261.

    • Author Contributions: Conception and design: R.S. Braithwaite, M.S. Roberts, C.L. Gibert, M.C. Rodriguez-Barradas, A. Schaefer, A.C. Justice.

    • Analysis and interpretation of the data: R.S. Braithwaite, M.S. Roberts, C.C. Chang, M.B. Goetz, C.L. Gibert, M.C. Rodriguez-Barradas, S. Shechter, R. Koppenhaver, A.C. Justice.

    • Drafting of the article: R.S. Braithwaite, C.C. Chang, C.L. Gibert, A.C. Justice.

    • Critical revision of the article for important intellectual content: R.S. Braithwaite, M.S. Roberts, M.B. Goetz, C.L. Gibert, M.C. Rodriguez-Barradas, A.C. Justice.

    • Final approval of the article: R.S. Braithwaite, M.S. Roberts, C.C. Chang, M.B. Goetz, C.L. Gibert, M.C. Rodriguez-Barradas, S. Shechter, A.C. Justice.

    • Provision of study materials or patients: A.C. Justice.

    • Statistical expertise: C.C. Chang, R. Koppenhaver, A.C. Justice.

    • Obtaining of funding: R.S. Braithwaite.

    • Administrative, technical, or logistic support: K. Nucifora, A.C. Justice.

    • Collection and assembly of data: K. Nucifora, R. Koppenhaver.

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    1. Ann Intern Med February 5, 2008 vol. 148 no. 3 178-185
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