The Association of HIV Susceptibility Testing With Survival Among HIV-Infected Patients Receiving Antiretroviral Therapy: A Cohort Study

  1. Frank J. Palella, Jr., MD;
  2. Carl Armon, MSPH;
  3. Kate Buchacz, PhD, MPH;
  4. Stephen R. Cole, PhD;
  5. Joan S. Chmiel, PhD;
  6. Richard M. Novak, MD;
  7. Kathleen Wood, BSN;
  8. Anne C. Moorman, BSN;
  9. John T. Brooks, MD; and
  10. for the HOPS (HIV Outpatient Study) Investigators*
  1. From Northwestern University Feinberg School of Medicine and University of Illinois College of Medicine at Chicago, Chicago, Illinois; Cerner Corporation, Vienna, Virginia; Centers for Disease Control and Prevention, Atlanta, Georgia; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

    Abstract

    Background: HIV-1 genotypic and phenotypic susceptibility testing (GPT) optimizes antiretroviral selection, but its effect on survival is unknown.

    Objective: To evaluate the association between GPT and survival.

    Design: Cohort study.

    Setting: 10 U.S. HIV clinics.

    Patients: 2699 HIV-infected patients eligible for GPT (plasma HIV RNA level >1000 copies/mL) seen from 1999 through 2005.

    Measurements: Demographic characteristics, clinical factors, GPT use, all-cause mortality, and crude and adjusted hazard ratios (HRs) for the association of GPT with survival.

    Results: Patients were followed for a median of 3.3 years; 915 (34%) had GPT. Patients who had GPT had lower mortality rates than those who did not (2.0 vs. 2.7 deaths per 100 person-years). In standard Cox models, GPT was associated with improved survival (adjusted HR, 0.69 [95% CI, 0.51 to 0.94]; P = 0.017) after controlling for demographic characteristics, CD4+ cell count, HIV RNA level, and intensity of clinical follow-up. In subgroup analyses, GPT was associated with improved survival for the 2107 highly active antiretroviral therapy (HAART)–experienced patients (2.2 vs. 3.2 deaths per 100 person-years for patients who had GPT vs. those who did not have GPT; adjusted HR, 0.60 [CI, 0.43 to 0.82]; P = 0.002) and for the 921 triple antiretroviral class–experienced patients (2.1 vs. 3.1 deaths per 100 person-years; adjusted HR, 0.61 [CI 0.40 to 0.93]; P = 0.022). Marginal structural models supported associations between GPT and improved survival in the overall cohort (adjusted HR, 0.54; P = 0.001) and in the HAART-experienced group (adjusted HR, 0.56; P = 0.003).

    Limitations: Use of GPT was not randomized. Residual confounding may exist.

    Conclusion: Use of GPT was independently associated with improved survival among HAART-experienced patients.

    Primary Funding Source: Centers for Disease Control and Prevention.

    Article and Author Information

    • Disclaimer: The findings and conclusions in this paper are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

    • Grant Support: By the Centers for Disease Control and Prevention (contract no. 200-2006-18797).

    • Potential Financial Conflicts of Interest: None disclosed.

    • Reproducible Research Statement: Study protocol and statistical code: Available from the authors. Data set: The HOPS is a public-use data set and is available to readers. However, confidentiality protections that govern the HOPS data require authors to strip record identifiers; it will therefore take some time to make these data available. In addition, the CDC's heightened security procedures require persons who want to analyze HOPS data to 1) prepare a written proposal for CDC review and approval, 2) sign confidentiality and data use agreements, 3) conduct analyses in Atlanta, and 4) go through CDC security clearance for access to facilities. The authors would be happy to facilitate these procedures for persons interested in conducting analyses with HOPS project data and welcome these requests.

    • Requests for Single Reprints: Frank J. Palella Jr., MD, Division of Infectious Diseases, Northwestern University, Feinberg School of Medicine, 645 North Michigan Avenue, Suite 900, Chicago, IL 60611; e-mail, f-palella{at}northwestern.edu.

    • Current Author Addresses: Dr. Palella: Division of Infectious Diseases, Northwestern University, Feinberg School of Medicine, 645 North Michigan Avenue, Suite 900, Chicago, IL 60611.

    • Mr. Armon: PO Box 1677, Boulder, CO 80306-1677.

    • Drs. Buchacz and Brooks: Epidemiology Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, MS E-45, Atlanta, GA 30333.

    • Dr. Cole: Campus Box 7435, Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7435.

    • Dr. Chmiel: Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, Suite 1102, 680 North Lake Shore Drive, Chicago, IL 60611-4402.

    • Dr. Novak: 1801 West Taylor Street, Suite 3D, Chicago, IL 60612.

    • Ms. Wood: Cerner Corporation, 1953 Gallows Road, Suite 500, Vienna, VA 22182.

    • Ms. Moorman: National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Division of Viral Hepatitis, Epi/Surveillance Branch, Mailstop G-37, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333.

    • Author Contributions: Conception and design: F.J. Palella, K. Buchacz, S.R. Cole, J.S. Chmiel, R.M. Novak, A.C. Moorman, J.T. Brooks.

    • Analysis and interpretation of the data: F.J. Palella, C. Armon, K. Buchacz, S.R. Cole, J.S. Chmiel, R.M. Novak, J.T. Brooks.

    • Drafting of the article: F.J. Palella, C. Armon, S.R. Cole, J.S. Chmiel, J.T. Brooks.

    • Critical revision of the article for important intellectual content: F.J. Palella, C. Armon, K. Buchacz, S.R. Cole, J.S. Chmiel, R.M. Novak, J.T. Brooks.

    • Final approval of the article: F.J. Palella, C. Armon, K. Buchacz, S.R. Cole, J.S. Chmiel, R.M. Novak, K. Wood, A.C. Moorman, J.T. Brooks.

    • Statistical expertise: C. Armon, K. Buchacz, S.R. Cole, J.S. Chmiel.

    • Obtaining of funding: K. Wood, J.T. Brooks.

    • Administrative, technical, or logistic support: K. Wood, A.C. Moorman.

    • Collection and assembly of data: K. Wood, A.C. Moorman.

    • ↵* For a list of the HOPS investigators, see Appendix 1.

    Comments on This Article

    • HIV SusceptibilityTesting With Survival Among HIV-Infected Patients Receiving Antiretroviral Therapy
      • Massimo Arlotti and
      • Andrea Boschi
      Ann Intern Med published online August 17, 2009
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    1. Ann Intern Med July 21, 2009 vol. 151 no. 2 73-84
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