Elevated CD8 Counts During HAART Are Associated With HIV Virologic Treatment Failure

Krantz, Elizabeth M MS*†; Hullsiek, Katherine Huppler PhD*†; Okulicz, Jason F MD*‡; Weintrob, Amy C MD*§; Agan, Brian K MD*; Crum-Cianflone, Nancy F MD, MPH*‖; Ganesan, Anuradha MBBS, MPH*¶; Ferguson, Tomas M MD*#; Hale, Braden R MD, MPH***; the Infectious Disease Clinical Research Program HIV Working Group

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e318221c62a
Clinical Science
Abstract

Objective: To evaluate whether elevated CD8 counts are associated with increased risk of virologic treatment failure in HIV-infected individuals.

Design: Retrospective cohort study.

Methods: US Military HIV Natural History Study participants who initiated highly active antiretroviral therapy (HAART) in 1996-2008 had 6- and 12-month post-HAART HIV RNA <400 copies per milliliter, ≥2 subsequent HIV viral loads and a baseline CD8 count were eligible (n = 817). Baseline was 12 months after the start of HAART, virologic failure (VF) was defined as confirmed HIV RNA ≥400 copies per milliliter, and CD8 counts ≥1200 cells per cubic millimeter were considered elevated. Cox models were used to examine the effect of baseline and time-updated CD8 counts on VF.

Results: There were 216 failures for a rate of 5.6 per 100 person-years [95% confidence interval (CI): 4.9 to 6.4]. Among those initiating HAART in 2000-2008, the participants with elevated baseline CD8 counts had significantly greater risk of VF compared with those with baseline CD8 counts ≤600 cells per cubic millimeter [hazard ratio (HR) = 2.68, 95% CI: 1.13 to 6.35]. The participants with elevated CD8 counts at >20% of previous 6-month follow-up visits had a greater risk of failure at the current visit than those who did not (HR = 1.53, 95% CI: 1.14 to 2.06). Those with CD8 counts that increased after the start of HAART had a greater risk of failure than those with CD8 counts that decreased or remained the same (HR = 1.59, 95% CI: 1.19 to 2.13).

Conclusions: Initial or serial elevated CD8 counts while on HAART or an increase in CD8 counts from HAART initiation may be early warnings for future treatment failure.

Author Information

From the *Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD; †Division of Biostatistics, University of Minnesota, Minneapolis, MN; ‡Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, TX; §Infectious Disease Service, Walter Reed Army Medical Center, Washington, DC; ‖Infectious Disease Clinic, Naval Medical Center San Diego, San Diego, CA; ¶Infectious Disease Clinic, National Naval Medical Center, Bethesda, MD; #Infectious Disease Service, Tripler Army Medical Center, Honolulu, HI; and **Naval Health Research Center, San Diego, CA.

Received for publication January 27, 2011; accepted April 27, 2011.

Supported by the Infectious Disease Clinical Research Program (IDCRP; IDCRP-000-19), a Department of Defense program executed through the Uniformed Services University of the Health Sciences. This project has been funded in whole, or in part, with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under Inter-Agency Agreement Y1-AI-5072.

Presented in part at the 48th Annual Meeting of the Infectious Diseases Society of America in Vancouver, British Columbia, Canada on October 23, 2010.

The authors have no conflicts of interest to disclose.

The content and views expressed in this publication are the sole responsibility of the authors and does not necessarily reflect the views or policies of the NIH or the Department of Health and Human Services, the DoD or the Departments of the Army, Navy, Air Force, Department of Defense, nor the U.S. Government. Mention of trade names, commercial products, or organizations does not imply endorsement by the US Government.

Correspondence to: Capt Braden R. Hale, MD, MPH, Naval Health Research Center, Code 165, 140 Sylvester Road, San Diego 92106, CA (e-mail: Braden.Hale@med.navy.mil).

© 2011 Lippincott Williams & Wilkins, Inc.