Low sensitivity of total lymphocyte count as a surrogate marker to identify antepartum and postpartum Indian women who require antiretroviral therapy

BACKGROUND: Some studies support the use of total lymphocyte count (TLC) as a surrogate marker for CD4 cell count to guide antiretroviral therapy (ART) initiation. However, most of these studies have focused on nonpregnant adults. In light of expanding ART access through prevention of mother-to-child transmission (PMTCT)-plus programs in resource-limited settings, we assessed the sensitivity, specificity, and positive predictive value (PPV) of TLC for predicting low CD4 counts in antepartum and postpartum women in Pune, India. METHODS: CD4, TLC, and hemoglobin were measured at third trimester, delivery, and 6, 9, and 12 months postpartum (PP) in a cohort of 779 HIV-infected women. Optimal TLC cutoff for predicting CD4 <200 cells/mm was determined via logistic regression where sensitivity, specificity, PPV, and an area under the receiver operating characteristic (ROC) curve were calculated. RESULTS: Among the 779 women enrolled, 16% had WHO clinical stage 2 or higher and 7.9% had CD4 <200 cells/mm. Using 2689 TLC-CD4 pairs, the sensitivity, specificity, and PPV of TLC <1200 cells/mm for predicting CD4 <200 cells/mm was 59%, 94%, and 47%, respectively. The sensitivity of TLC <1200 cells/mm cutoff ranged between 57% and 62% for time points evaluated. Addition of hemoglobin <12 g/dL or <11 g/dL increased the sensitivity of TLC to 74% to 92% for predicting CD4 <200 cells/mm but decreased the specificity to 33% to 69% compared to TLC alone. A combination of TLC, hemoglobin, and WHO clinical staging had the highest sensitivity but lowest specificity compared to other possible combinations or use of TLC alone. The sensitivity and specificity of TLC <1200 cells/mm to predict a CD4 <350 cells/mm was 31% and 99%, respectively. CONCLUSIONS: Our data suggest that antepartum and PP women with TLC <1200 cells/mm are likely to have CD4 <200 cells/mm. However, the sensitivity of this TLC cutoff was low. Between 45% and 64% of antepartum and PP women requiring initiation of ART may not be identified by using TLC alone as a surrogate marker for CD4 <200 cells/mm. The WHO-recommended TLC cutoff of <1200 cells/mm is not optimal for identifying antepartum and PP Indian women who require ART.