CD4 Lymphocyte Percentage and HIV Disease Progression
Abstract & Commentary
By Dean L. Winslow, MD, FACP, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center and Clinical Professor of Medicine, Stanford University School of Medicine, Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
Dr. Winslow is a consultant for Bayer Diagnostics and Pfizer/Agouron, and is on the speaker’s bureau for Pfizer/Agouron.
Synopsis: In a cohort study of 788 patients, CD4 lymphocyte percentage predicted disease progression in patients who initiated antiretroviral therapy with > 350 CD4 lymphocytes/mm3.
Source: Hulgan T, et al. CD4 Lymphocyte Percentage Predicts Disease Progression in HIV-Infected Patients Initiating Highly Active Antiretroviral Therapy With CD4 Lymphocyte Counts > 350 Lymphocytes/mm3. J Infect Dis. 2005;192:950-957.
This study out of Vanderbilt examined a cohort of 788 eligible patients from their clinic who received their first highly active antiretroviral therapy (HAART) regimen for at least 30 days between January 1998 and January 2003 and had a baseline CD4 lymphocyte determination in the 180 days prior to initiating antiretrovirals or within 45 of starting treatment. Patients were stratified by absolute CD4 count of < 200, 200-350, 351-500, and > 500 lymphocytes/mm3. They were also stratified by CD4 lymphocyte percentage > 14%, 14%-20%, 21%-28%, and > 28%. HAART was defined as a regimen containing either a protease inhibitor and/or a non-nucleoside reverse transcriptase (RT) inhibitor. Both treatment naïve and nucleoside analogue reverse transcriptase inhibitor (NRTI) experienced patients were included.
Using the combined end point of progression to an AIDS-defining illness or death, overall analysis of the cohort confirmed the significantly greater rate of clinical end points in patients who had baseline CD4 counts of < 200 vs. those with CD4 counts > 200 and between those with CD4 percentages of < 17% vs. >17% with both analyses resulting in P < .0001 by log-rank test.
Commentary
Highly active antiretroviral therapy has been the single most important factor responsible for the dramatically decreased morbidity and mortality associated with HIV infection. Although newer antiretroviral (ARV) agents tend to be more potent and less toxic than the first generation of ARVs, antiretroviral therapy comes with a price tag, both literally and in terms of potentially developing drug resistance as well as early and late toxicities. In view of this, most recent guidelines use a combination of absolute CD4 lymphocyte count and HIV RNA level as criteria for initiating HAART.1 Current guidelines recommend HAART for all patients with CD4 < 200, those patients with clinical symptoms, and generally recommend individualizing the decision to treat individuals who have CD4 lymphocyte counts between 200 and 350 cells/mm3. ARV treatment of patients with CD4 > 350 is generally not recommended.
The most striking finding from this study was that CD4 lymphocyte percentage < 17% was associated with an increased risk of clinical disease progression in the cohort of 223 patients with baseline CD4 lymphocyte counts > 350 and that CD4 < 17% was the strongest predictor of disease progression in this cohort. In individuals with lower absolute lymphocyte counts, CD4% seemed to add little to the prognostic information gained from absolute lymphocyte count. Due to the univariate nature of the Cox analysis, the authors state that the association of nonwhite race with disease progression was largely explained by the lower baseline CD4 counts observed in nonwhites in this cohort.
Sometimes new data make us rediscover the old. At least two studies from the pre-HAART era found that CD4 lymphocyte percentage was more stable and had greater prognostic significance than absolute CD4 lymphocyte count.2,3 The finding in the Hulgan study that almost 50% of patients who had absolute CD4 counts >350 with CD4% < 17% developed an AIDS-defining illness or died over approximately 1700 days of follow up is an important observation. I will definitely pay closer attention to this phenomenon in my own practice, and may have a lower threshold now than previously in considering this group of patients for ARV therapy.
References
- Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents. Department of Health and Human Services 2003. Updated March 23, 2004.
- Taylor JM, et al. CD4 Percentage, CD4 Number, and CD4:CD8 Ratio in HIV Infection: Which to Choose and How to Use. J Acquir Immune Defic Syndr. 1989;2:114-124.
- Burcham J, et al. CD4% is the Best Predictor of Development of AIDS in a Cohort of HIV-Infected Homosexual Men. AIDS. 1991;5:365-372.
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