Abstract

ObjectivesCounts of absolute CD4+ T lymphocytes (CD4+ T cells) are known to be highly variable in untreated HIV-infected individuals, but there are no data in virologically-suppressed individuals. We investigated CD4+ T cell variability in stable, virologically-suppressed, HIV-1 infected adults on combination antiretroviral therapy (cART).MethodsFrom a large hospital database we selected patients with stable virological suppression on cART for >3 years with >10 CD4+ T cell measurements performed over a further >2 years; and a control group of 95 patients not on cART.ResultsWe identified 161 HIV-infected patients on cART without active HCV or HBV infection, with stable virological suppression for a median of 6.4 years. Over the study period 88 patients had reached a plateau in their absolute CD4+ T cell counts, while 65 patients had increasing and 8 patients had decreasing absolute CD4+ T cell counts. In patients with plateaued CD4+ T cell counts, variability in absolute CD4+ T cell counts was greater than in percent CD4+ T cells (median coefficient of variation (CV) 16.6% [IQR 13.8-20.1%] and CV 9.6% [IQR 7.4-13.0%], respectively). Patients with increasing CD4+ T cell counts had greater variability in absolute CD4+ T cell counts than those with plateaued CD4 T cell counts (CV 19.5% [IQR 16.1-23.8%], p<0.001) while there was no difference in percent CD4+ T cell variability between the two groups. As previously reported, untreated patients had CVs significantly higher than patients on cART (CVs of 21.1% [IQR 17.2-32.0%], p<0.001 and 15.2% (IQR 10.7-20.0%), p<0.001, respectively). Age or sex did not affect the degree of CD4+ variation.ConclusionsAdults with stable, virologically-suppressed HIV infection continue to have significant variations in individual absolute CD4+ T cell and percent CD4+ T cell counts; this variation can be of clinical relevance especially around CD4+ thresholds. However, the variation seen in individuals on cART is substantially less than in untreated subjects.

Highlights

  • The decision to commence combination antiretroviral therapy for patients with asymptomatic human immunodeficiency virus-1 (HIV) infection may be based primarily on the absolute CD3+CD4+ T lymphocyte count (CD4+ T cell count), the percent CD4 + T cells and HIV viral load may be considered [1]

  • We identified 161 HIV-infected patients on combination antiretroviral therapy (cART) without active HCV or HBV infection, with stable virological suppression for a median of 6.4 years

  • Patients with increasing CD4+ T cell counts had greater variability in absolute CD4+ T cell counts than those with plateaued CD4 T cell counts (CV 19.5% [interquartile range (IQR) 16.1-23.8%], p

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Summary

Introduction

The decision to commence combination antiretroviral therapy (cART) for patients with asymptomatic human immunodeficiency virus-1 (HIV) infection may be based primarily on the absolute CD3+CD4+ T lymphocyte count (CD4+ T cell count), the percent CD4 + T cells and HIV viral load may be considered [1]. Several studies have reported wide, intra-individual variability in CD4+ T cell counts in treatment-naïve, HIV-infected individuals due to both laboratory and physiological factors [4,5,6]. This variability, up to 18–25%, limits the utility of a single CD4+ T cell measurement for clinical decision-making [4, 7, 8]. This issue is problematic in resource poor settings where often only a single CD4+ T cell count is available prior to initiating therapy. The laboratory process of CD4+ T cell testing has inherent imprecision, related to pipetting errors, during quantification of both total lymphocyte count and to a lesser degree the percent CD4+ T cell number [6, 8]

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