R. Scott Braithwaite, MD, MSc; Mark S. Roberts, MD, MPP; Chung Chou H. Chang, PhD; Matthew Bidwell Goetz, MD; Cynthia L. Gibert, MD, MSc; Maria C. Rodriguez-Barradas, MD; Steven Shechter, PhD; Andrew Schaefer, PhD; Kimberly Nucifora, MS; Robert Koppenhaver, MS; Amy C. Justice, MD, PhD
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@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.
The optimal threshold for initiating HIV treatment is unclear.
To compare different thresholds for initiating HIV treatment.
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).
Veterans Aging Cohort Study (5742 HIV-infected patients and 11 484 matched uninfected controls) and published reports.
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).
Alternative thresholds for initiating antiretroviral therapy (CD4 counts of 200, 350, and 500 cells/mm3).
Life-years and quality-adjusted life-years (QALYs).
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).
Findings favoring early treatment were generally robust.
Results favoring later treatment may not be valid. The findings may not be generalizable to women.
This simulation suggests that earlier initiation of combination antiretroviral therapy is often favored compared with current recommendations.
Braithwaite RS, Roberts MS, Chang CCH, Goetz MB, Gibert CL, Rodriguez-Barradas MC, et al. Influence of Alternative Thresholds for Initiating HIV Treatment on Quality-Adjusted Life Expectancy: A Decision Model. Ann Intern Med. 2008;148:178–185. doi: 10.7326/0003-4819-148-3-200802050-00004
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Published: Ann Intern Med. 2008;148(3):178-185.
HIV, Infectious Disease.
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