CD4 Percentage is an Independent Predictor of Survival in Patients
CD4 Percentage is an Independent Predictor of Survival in Patients
Objective: To determine the prognostic value of baseline CD4 percentage in terms of patient survival in comparison to absolute CD4 cell counts for HIV-positive patients initiating highly active antiretroviral therapy (HAART).
Methods: A population-based cohort study of 1623 antiretroviral therapy-naïve HIV-positive individuals who initiated HAART between 1 August 1996 and 30 June 2002 was conducted. Cumulative mortality rates were estimated using Kaplan-Meier methods. Cox proportional hazards regression was used to model the effect of baseline CD4 strata and CD4 percentage strata and other prognostic variables on survival. A subgroup analysis was conducted on 417 AIDS-free subjects with baseline CD4 counts between 200 and 350 cells/μL.
Results: In multivariate models, low CD4 percentages were associated with increased risk of death [CD4%<5, relative hazard (RH) = 4.46; CD4% 5-14, RH = 2.43; P<0.01 for both] when compared with those subjects with an initial CD4 fraction of 15% or greater, but had less predictive value than absolute CD4 counts. In subgroup analyses where absolute CD4 strata were not associated with mortality, a baseline CD4 fraction below 15% [RH = 2.71; 95% confidence interval (CI) 1.20-6.10], poor adherence to therapy and baseline viral load >100 000 HIV-1 RNA copies/mL were associated with an increased risk of death.
Conclusion: CD4 percentages below 15% are independent predictors of mortality in AIDS-free patients starting HAART, including those with CD4 counts between 200 and 350 cells/μL. CD4 percentage should be considered for inclusion in guidelines used to determine when to start therapy.
Recently revised guidelines from the International AIDS Society-USA (IAS-USA) recommend that highly active antiretroviral therapy (HAART) should be started in all treatment-naïve individuals with symptomatic HIV disease, as well as those individuals who are asymptomatic, but who have CD4 counts below 200 cells/μL. For asymptomatic individuals with CD4 counts above 200 cells/μL, the decision of when to start treatment should be individualized and should take into account the rate of decline in CD4 cell count, HIV plasma RNA levels, and the individual risks of toxicity and drug interactions, as well as the patient's interest in antiretroviral (ARV) therapy and their potential to adhere to therapy. Other recommendations have suggested that this threshold should be 350 cells/μL, given the evidence that delaying treatment until CD4 counts drop below 200 cells/μL is associated with an increased risk of mortality.
The number of CD4 cells expressed as a percentage of the total number of lymphocytes has been used anecdotally by clinicians as another measure to suggest when ARV therapy should be started in asymptomatic individuals with CD4 counts above 200 cells/μL. However, the validity of this measure in terms of its association with survival in patients on HAART has not been evaluated in large prospective studies. Three studies conducted in the pre-HAART era did find that CD4 percentage was a better predictor of disease progression than absolute counts and another found that a CD4 fraction of less than 14% was associated with life-threatening opportunistic infections such as Pneumocystis carinii pneumonia (PCP). In another study, patients with discordant absolute CD4 cell counts and percentages displayed a trend towards increased incidence of PCP and mortality, but these differences were not statistically significant.
However, there have been few studies that have compared the relative values of absolute CD4 count and CD4 percentage with respect to their utility in predicting clinically significant outcomes in patients beginning HAART. One recently published study found that CD4 percentage did not provide further value over absolute count in predicting risk of a subsequent AIDS-defining illness in 2185 patients who were followed for a maximum of 6 months after obtaining a discordant absolute CD4 and CD4 percentage laboratory result. However, not all patients (59% in total) in this study received HAART.
As CD4 percentage is commonly included in laboratory reports provided to clinicians of absolute CD4 cell counts at baseline, we designed a study to compare its clinical utility in predicting disease progression with that of absolute CD4 cell count in a cohort of individuals starting HAART in British Columbia, Canada. Furthermore, we analysed the utility of CD4 percentage as a prognostic factor in a subgroup of individuals who would be considered for HAART therapy using current guidelines, but for whom the decision to treat is not yet clearly defined and where absolute CD4 cell counts have been shown not to have predictive value.
Abstract and Introduction
Abstract
Objective: To determine the prognostic value of baseline CD4 percentage in terms of patient survival in comparison to absolute CD4 cell counts for HIV-positive patients initiating highly active antiretroviral therapy (HAART).
Methods: A population-based cohort study of 1623 antiretroviral therapy-naïve HIV-positive individuals who initiated HAART between 1 August 1996 and 30 June 2002 was conducted. Cumulative mortality rates were estimated using Kaplan-Meier methods. Cox proportional hazards regression was used to model the effect of baseline CD4 strata and CD4 percentage strata and other prognostic variables on survival. A subgroup analysis was conducted on 417 AIDS-free subjects with baseline CD4 counts between 200 and 350 cells/μL.
Results: In multivariate models, low CD4 percentages were associated with increased risk of death [CD4%<5, relative hazard (RH) = 4.46; CD4% 5-14, RH = 2.43; P<0.01 for both] when compared with those subjects with an initial CD4 fraction of 15% or greater, but had less predictive value than absolute CD4 counts. In subgroup analyses where absolute CD4 strata were not associated with mortality, a baseline CD4 fraction below 15% [RH = 2.71; 95% confidence interval (CI) 1.20-6.10], poor adherence to therapy and baseline viral load >100 000 HIV-1 RNA copies/mL were associated with an increased risk of death.
Conclusion: CD4 percentages below 15% are independent predictors of mortality in AIDS-free patients starting HAART, including those with CD4 counts between 200 and 350 cells/μL. CD4 percentage should be considered for inclusion in guidelines used to determine when to start therapy.
Introduction
Recently revised guidelines from the International AIDS Society-USA (IAS-USA) recommend that highly active antiretroviral therapy (HAART) should be started in all treatment-naïve individuals with symptomatic HIV disease, as well as those individuals who are asymptomatic, but who have CD4 counts below 200 cells/μL. For asymptomatic individuals with CD4 counts above 200 cells/μL, the decision of when to start treatment should be individualized and should take into account the rate of decline in CD4 cell count, HIV plasma RNA levels, and the individual risks of toxicity and drug interactions, as well as the patient's interest in antiretroviral (ARV) therapy and their potential to adhere to therapy. Other recommendations have suggested that this threshold should be 350 cells/μL, given the evidence that delaying treatment until CD4 counts drop below 200 cells/μL is associated with an increased risk of mortality.
The number of CD4 cells expressed as a percentage of the total number of lymphocytes has been used anecdotally by clinicians as another measure to suggest when ARV therapy should be started in asymptomatic individuals with CD4 counts above 200 cells/μL. However, the validity of this measure in terms of its association with survival in patients on HAART has not been evaluated in large prospective studies. Three studies conducted in the pre-HAART era did find that CD4 percentage was a better predictor of disease progression than absolute counts and another found that a CD4 fraction of less than 14% was associated with life-threatening opportunistic infections such as Pneumocystis carinii pneumonia (PCP). In another study, patients with discordant absolute CD4 cell counts and percentages displayed a trend towards increased incidence of PCP and mortality, but these differences were not statistically significant.
However, there have been few studies that have compared the relative values of absolute CD4 count and CD4 percentage with respect to their utility in predicting clinically significant outcomes in patients beginning HAART. One recently published study found that CD4 percentage did not provide further value over absolute count in predicting risk of a subsequent AIDS-defining illness in 2185 patients who were followed for a maximum of 6 months after obtaining a discordant absolute CD4 and CD4 percentage laboratory result. However, not all patients (59% in total) in this study received HAART.
As CD4 percentage is commonly included in laboratory reports provided to clinicians of absolute CD4 cell counts at baseline, we designed a study to compare its clinical utility in predicting disease progression with that of absolute CD4 cell count in a cohort of individuals starting HAART in British Columbia, Canada. Furthermore, we analysed the utility of CD4 percentage as a prognostic factor in a subgroup of individuals who would be considered for HAART therapy using current guidelines, but for whom the decision to treat is not yet clearly defined and where absolute CD4 cell counts have been shown not to have predictive value.
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