Survival Benefit of Initiating Antiretroviral Therapy in HIV-Infected Persons in Different CD4+ Cell Strata

  1. Frank J. Palella, Jr., MD;
  2. Maria Deloria-Knoll, PhD;
  3. Joan S. Chmiel, PhD;
  4. Anne C. Moorman, BSN, MPH;
  5. Kathleen C. Wood, BSN;
  6. Alan E. Greenberg, MD, MPH;
  7. Scott D. Holmberg, MD, MPH; and
  8. the HIV Outpatient Study (HOPS) Investigators*
  1. From Northwestern University, Chicago, Illinois; National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; and APACHE Medical Systems, Cerner Corporation, Vienna, Virginia.

    Abstract

    Background: Optimal timing of antiretroviral therapy (ART) initiation for HIV-infected persons remains unclear.

    Objective: To assess survival benefit of initiating ART at different CD4+ cell counts.

    Design: Prospective observational study.

    Setting: U.S. clinics in the HIV Outpatient Study (HOPS).

    Patients: HIV-infected patients with CD4+ cell counts, plasma HIV RNA viral load, and ART use recorded from January 1994 through March 2002.

    Measurements: Before initiation of ART, patients were grouped by their CD4+ cell counts into three subgroups: 0.201 to 0.350 × 109 cells/L (n = 399), 0.351 to 0.500 × 109 cells/L (n = 327), and 0.501 to 0.750 × 109 cells/L (n = 122). We compared mortality rates for each CD4+ subgroup among patients who initiated ART and patients who delayed ART until reaching a lower CD4+ subgroup.

    Results: Mortality rates for 340 patients who initiated ART and 59 who delayed ART in the CD4+ subgroup of 0.201 to 0.350 × 109 cells/L were 15.4 and 56.4 deaths per 1000 person-years, respectively (rate ratio, 0.27 [95% CI, 0.14 to 0.55]; P < 0.001). For the CD4+ subgroup of 0.351 to 0.500 × 109 cells/L, mortality rates for 240 patients who initiated ART and 887 who delayed ART were 10.0 and 16.6 deaths per 1000 person-years, respectively (rate ratio, 0.61 [CI, 0.22 to 1.67]; P = 0.17). For the CD4+ subgroup of 0.501 to 0.750 × 109 cells/L, mortality rates in 55 patients who initiated ART and 67 who delayed ART were 7.5 and 3.1 deaths per 1000 person-years, respectively (rate ratio, 1.20 [CI, 0.17 to 8.53]; P > 0.2). Patients in the 0.201 to 0.350 × 109 cells/L and 0.351 to 0.500 × 109 cells/L CD4+ subgroups who initiated ART were more likely than those who delayed ART to achieve an undetectable HIV viral load (P = 0.03 and 0.04, respectively).

    Conclusions: Among HIV-infected persons with CD4+ cell counts of 0.201 to 0.350 × 109 cells/L, initiating ART is associated with reduced mortality compared with delaying such therapy. Survival benefits of earlier ART initiation (at CD4+ cell counts of 0.351 to 0.500 × 109 cells/L) are possible.

    *For the HOPS Investigators, see Appendix.

    Article and Author Information

    • Acknowledgment: The authors thank John P. Phair, MD, Professor Emeritus of Medicine, The Feinberg School of Medicine, Northwestern University, for his ongoing support, insight, and sage advice.

    • Grant Support: By the Centers for Disease Control and Prevention (contract 200-2001-00133), Atlanta, Georgia.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Frank J. Palella Jr., MD, Division of Infectious Diseases, The Feinberg School of Medicine, Northwestern University, 676 North Saint Clair, Suite 200, Chicago, IL 60611; e-mail, f-palella{at}northwestern.edu.

    • Current Author Addresses: Dr. Palella: Division of Infectious Diseases, The Feinberg School of Medicine, Northwestern University, 676 North Saint Clair, Suite 200, Chicago, IL 60611.

    • Drs. Deloria-Knoll and Chmiel: Department of Preventive Medicine, The Feinberg School of Medicine, Northwestern University, 680 North Lake Shore Drive, Suite 1102, Chicago, IL 60611.

    • Ms. Moorman, Dr. Greenberg, and Dr. Holmberg: Centers for Disease Control and Prevention, Mailstop E-45, 1600 Clifton Road, Atlanta, GA 30333.

    • Ms. Wood: Cerner Corporation, 2800 Rockcreek Parkway, Kansas City, MO 64117.

    • Author Contributions: Conception and design: F.J. Palella, M. Deloria-Knoll, J.S. Chmiel, A.C. Moorman, S.D. Holmberg.

    • Analysis and interpretation of the data: F.J. Palella, M. Deloria-Knoll, J.S. Chmiel, A.C. Moorman, A.E. Greenberg, S.D. Holmberg.

    • Drafting of the article: F.J. Palella.

    • Critical revision of the article for important intellectual content: F.J. Palella, M. Deloria-Knoll, J.S. Chmiel, A.C. Moorman, A.E. Greenberg, S.D. Holmberg.

    • Final approval of the article: F.J. Palella, M. Deloria-Knoll, J.S. Chmiel, A.C. Moorman, K.C. Wood, A.E. Greenberg, S.D. Holmberg.

    • Provision of study materials or patients: F.J. Palella.

    • Statistical expertise: M. Deloria-Knoll, J.S. Chmiel.

    • Obtaining of funding: K.C. Wood.

    • Administrative, technical, or logistic support: F.J. Palella, A.C. Moorman, K.C. Wood, S.D. Holmberg.

    • Collection and assembly of data: F.J. Palella, A.C. Moorman, K.C. Wood, S.D. Holmberg.

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    1. Ann Intern Med April 15, 2003 vol. 138 no. 8 620-626
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