Evaluating Total Lymphocyte Counts and Other Hematological Parameters as a Substitute for CD4 Counts in the Management of HIV Patients in Northeastern Nigeria

Abstract

This study was designed to validate or refute the reliability of total lymphocyte count (TLC) and other hematological parameters as a substitute for CD4 cell counts. Participants consisted of two groups, including 416 antiretroviral naive (G1) and 328 antiretroviral experienced (G2) patients. CD4+ T cell counts were performed using a Cyflow machine. Hematological parameters were analyzed using a hematology analyzer. The median ± SEM CD4 count (range) of participants in G1 was 199 ± 10.9 (5-1840 cells/µL) and the median ± SEM TLC (range) was 1. 61 ± 0.05 (0.07-6.63 × 10 3 /µL). The corresponding values among G2 were 421 ± 15.8 (13-1801) and 2.13 ± 0.04 (0.06-5.58), respectively. Using a threshold value of 1.2 × 10 3 /µL for TLC alone, the sensitivity of G1 was 88.4% (specificity (SP) 67.4%, the positive predictive value (PPV) 53.5% and negative predictive value (NPV) of 93.2% for CD4 , 200 cells/µL, the sensitivity for G2 was 83.3%, SP 85.3%, PPV 23.8%, and NPV of 93.2%. Using multiple parameters, including TLC , 1.2 × 10 3 /µL, hemoglobin , 10 g/dL, and platelets , 150 × 10 3 /L, the sensitivity increased to 96.0% (SP, 82.7%; PPV, 80%; NPV, 96.7%) among G1, while no change was observed in the G2 cohort. TLC , 1.2 × 10 3 /µL alone is an insensitive predictor of CD4 count of , 200 cells/µL. Incorporating hemoglobin , 10 g/dL, and platelets , 150 × 10 3 /L enhances the ability of TLC , 1.2 × 10 3 /µL to predict CD4 count , 200 cells/µL among the antiretroviral-naïve cohort. We recommend the use of multiple, inexpensively measured hematological parameters in the form of an algorithm for predicting CD4 count level.

Development of an algorithm of haematologic parameters as surrogate markers for CD4 cell count in resource-limited settings

“…The risk of false negative results in this study (87%), made TLC of less than 1200 cell/mm 3 a relatively insensitive predictor of the CD4 cell count <350 cells/mm 3 . This is in agreement with several other studies (Buseri et al, 2012;Denue et al, 2013;Venkataramana, 2013). On adjusting the TLC using different cut-off points, there was a balance between the detection of patients qualifying for HAART and the burden of over-classifying people as requiring treatment at <2000 cells/mm 3 (sensitivity 71.5%, specificity 73.4%, PPV 69.1%), implying the ability to detect 7 in 10 patients in need of HAART.…”

“…The Mean±SD values of hematological parameters obtained in this study (Table 2) bore slight similarity with those from other African studies (Denue et al, 2013, Charles et al, 2014. However, CD4 + T cells value of 294.9±224 μL -1 obtained from this study was significantly higher than of the afore-mentioned studies.…”

“…Similarly, another study reported 91% sensitivity, 73% specificity, and 88% PPV for predicting a CD4 cell count of 200 cells/mm 3 using a multivariate model with similar parameters (TLC, haemoglobin level, platelet count, and sex) than when TLC was used alone (Chen et al, 2003). The most recent study in Nigeria demonstrated optimal sensitivity at 96.0% (SP, 82.7%; PPV,80%; NPV,96.7%) with the use of multiple parameters, TLC1.2×103/µL, haemoglobin<10 g/dL, and platelets <150×103/L to predict CD4 count <200 cells/unit (Denue et al, 2013). In contrast, a study in Nigeria combined correlation of total lymphocyte count, haemoglobin and haematocrit with CD4 and concluded that haematological parameters are not suitable for representing CD count (Charles et al, 2014).…”

“…One factor that could blunt the correlation between TLC and CD4 T cell count besides opportunistic infections, is that TLC captures both B and T cell subsets. Thus, a person with a low CD4 T cell count may show relatively high TLC if high amounts of B cells are expressed due to immune hyperactivation from exposure to the wide variety of circulating antigens, consequent on varieties of infections in HIV patients with severe immunosuppression (Denue et al, 2013).…”

“…TLC has been previously studied as a suitable surrogate for CD4 counts in the management of HIV. Several studies assessing the relationship between CD4 count and TLC have been done in sub-Saharan Africa (Githinji et al, 2011;Wondimeneh et al, 2012;Denue et al, 2013;Charles et al, 2014). These studies showed a significant correlation between TLC and CD4 count.…”