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

5 February 2008 | Volume 148 Issue 3 | Pages 178-185

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.

Editors' Notes Context Trials have not answered questions about optimal timing of HIV therapy, and many benefits and harms of therapy occur over time horizons that are longer than the trials. Early treatment may postpone AIDS, but it may also increase resistance and unnecessarily subject patients to the costs and toxicity of drugs. Contribution This computer simulation estimated that starting treatment earlier (CD4 count threshold of 500 cells/mm3) would provide greater unadjusted and quality-adjusted life expectancy than starting it later (at a CD4 count of 350 or 200 cells/mm3) for all patients age 30 years and for patients age 40 years who have a viral load greater than 30 000 copies/mL. Caution Increases in life expectancy were small, and the analysis did not consider costs. —The Editors

 

Author and Article Information

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.

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.