CD4+ T-Cell Count Monitoring Does Not Accurately Identify HIV-Infected
CD4+ T-Cell Count Monitoring Does Not Accurately Identify HIV-Infected
Background: CD4 T-lymphocyte (CD4) counts are widely used to monitor response to antiretroviral therapy (ART) in resource-limited settings. However, the utility of such monitoring in terms of predicting virologic response to therapy has been little studied.
Methods: We studied participants aged 18 years and older who initiated ART in Tororo, Uganda. CD4 counts, CD4 percentages, and viral load (VL) were examined at 6-monthly intervals. Various definitions of immunologic failure were examined to identify individuals with VLs ≥ 50, ≥ 500, ≥ 1000, or ≥ 5000 copies per milliliter at 6, 12, and 18 months after treatment initiation.
Results: One thousand sixty-three ART-naive persons initiated ART. The proportion of individuals with virologic failure ranged between 1.5% and 16.4% for each time point. The proportion with no increase in CD4 count from baseline did not differ between those with suppressed or unsuppressed VLs at 6, 18, and 24 months after ART initiation. No increase in CD4 cell counts at 6 months had a sensitivity of 0.04 [95% confidence interval (CI) 0.00 to 0.10] and a positive predictive value of 0.03 (95% CI 0.00 to 0.09) for identifying individuals with VL ≥ 500 copies per milliliter at 6 months. The best measure identified was an absolute CD4 cell count <125 cells per microliter at 21 months for predicting VL ≥ 500 copies per milliliter at 18 months which had a sensitivity of 0.13 (95% CI 0.01 to 0.21) and a positive predictive value of 0.29 (95% CI 0.10 to 0.44).
Conclusions: CD4 cell count monitoring does not accurately identify individuals with virologic failure among patients taking ART.
Treatment guidelines from the World Health Organization (WHO) regarding the use of antiretroviral therapy (ART) in resource-limited settings recommend the use of CD4 T-lymphocyte (CD4) counts to monitor response to therapy in programs where HIV-1 viral load (VL) testing is not available. Consequently, CD4 cell counts have become the most common laboratory method for evaluating eligibility for ART and monitoring response to treatment in such settings. The WHO guidelines recommend a change in drug regimen for individuals on ART who have a return of CD4 cell counts to pretherapy levels or a ≥ 50% decrease in CD4 cell counts from peak levels, both in the absence of intercurrent infections. The large majority of HIV-infected individuals will achieve virologic suppression in response to ART within the first year of treatment; therefore, monitoring ART response is used primarily to identify the minority of persons who fail to achieve an initial response to ART and to detect subsequent treatment failure after an initial response to therapy has occurred.
In high-income countries, treatment failure on ART is primarily defined as the failure to suppress VL or experiencing a VL rebound after initial suppression; immunologic parameters alone are not used to determine the need for drug regimen switches. An analysis from British Columbia, Canada, found that observing no increase in CD4 counts at 6 months had a sensitivity of 0.34 and a positive predictive value (PPV) of 0.75 for predicting failure to achieve 2 successive VL measurements <500 copies per milliliter in the first year on ART. Furthermore, the performance of immunologic parameters was even worse when attempting to predict VLs ≥ 50 copies per milliliter. However, the clinical performance of immunologic responses to ART, without concomitant virologic monitoring, in predicting response to therapy has been evaluated in very few resource-limited settings, where adherence rates, virologic suppression rates, and immunologic responses to ART may differ from those in high-income countries.
We designed a study to evaluate the clinical utility of immunologic parameters at 6, 12, and 18 months after ART initiation in identifying patients who fail to achieve or maintain virologic suppression on their primary ART regimen, using data from a home-based ART program in rural Uganda.
Background: CD4 T-lymphocyte (CD4) counts are widely used to monitor response to antiretroviral therapy (ART) in resource-limited settings. However, the utility of such monitoring in terms of predicting virologic response to therapy has been little studied.
Methods: We studied participants aged 18 years and older who initiated ART in Tororo, Uganda. CD4 counts, CD4 percentages, and viral load (VL) were examined at 6-monthly intervals. Various definitions of immunologic failure were examined to identify individuals with VLs ≥ 50, ≥ 500, ≥ 1000, or ≥ 5000 copies per milliliter at 6, 12, and 18 months after treatment initiation.
Results: One thousand sixty-three ART-naive persons initiated ART. The proportion of individuals with virologic failure ranged between 1.5% and 16.4% for each time point. The proportion with no increase in CD4 count from baseline did not differ between those with suppressed or unsuppressed VLs at 6, 18, and 24 months after ART initiation. No increase in CD4 cell counts at 6 months had a sensitivity of 0.04 [95% confidence interval (CI) 0.00 to 0.10] and a positive predictive value of 0.03 (95% CI 0.00 to 0.09) for identifying individuals with VL ≥ 500 copies per milliliter at 6 months. The best measure identified was an absolute CD4 cell count <125 cells per microliter at 21 months for predicting VL ≥ 500 copies per milliliter at 18 months which had a sensitivity of 0.13 (95% CI 0.01 to 0.21) and a positive predictive value of 0.29 (95% CI 0.10 to 0.44).
Conclusions: CD4 cell count monitoring does not accurately identify individuals with virologic failure among patients taking ART.
Treatment guidelines from the World Health Organization (WHO) regarding the use of antiretroviral therapy (ART) in resource-limited settings recommend the use of CD4 T-lymphocyte (CD4) counts to monitor response to therapy in programs where HIV-1 viral load (VL) testing is not available. Consequently, CD4 cell counts have become the most common laboratory method for evaluating eligibility for ART and monitoring response to treatment in such settings. The WHO guidelines recommend a change in drug regimen for individuals on ART who have a return of CD4 cell counts to pretherapy levels or a ≥ 50% decrease in CD4 cell counts from peak levels, both in the absence of intercurrent infections. The large majority of HIV-infected individuals will achieve virologic suppression in response to ART within the first year of treatment; therefore, monitoring ART response is used primarily to identify the minority of persons who fail to achieve an initial response to ART and to detect subsequent treatment failure after an initial response to therapy has occurred.
In high-income countries, treatment failure on ART is primarily defined as the failure to suppress VL or experiencing a VL rebound after initial suppression; immunologic parameters alone are not used to determine the need for drug regimen switches. An analysis from British Columbia, Canada, found that observing no increase in CD4 counts at 6 months had a sensitivity of 0.34 and a positive predictive value (PPV) of 0.75 for predicting failure to achieve 2 successive VL measurements <500 copies per milliliter in the first year on ART. Furthermore, the performance of immunologic parameters was even worse when attempting to predict VLs ≥ 50 copies per milliliter. However, the clinical performance of immunologic responses to ART, without concomitant virologic monitoring, in predicting response to therapy has been evaluated in very few resource-limited settings, where adherence rates, virologic suppression rates, and immunologic responses to ART may differ from those in high-income countries.
We designed a study to evaluate the clinical utility of immunologic parameters at 6, 12, and 18 months after ART initiation in identifying patients who fail to achieve or maintain virologic suppression on their primary ART regimen, using data from a home-based ART program in rural Uganda.