CD4+/CD8+ T Cell Ratio for Diagnosis of HIV-1 Infection in Infants: Women and Infants Transmission Study

Abstract

OBJECTIVE. In this study, we tested the hypothesis that the CD4+/CD8+ T cell ratio could predict HIV infection status in HIV-exposed infants. METHODS. CD4+/CD8+ T cell ratios were determined from data for live-born singleton infants who had been prospectively enrolled in the Women and Infants Transmission Study. Data for 2208 infants with known HIV infection status (179 HIV-infected and 2029 uninfected infants) were analyzed. RESULTS. Receiver operating characteristic curves indicated that the CD4+/CD8+ T cell ratio performed better than the proportion of CD4+ T cells for diagnosis of HIV infection as early as 2 months of age, and this relationship was unaffected by adjustment for maternal race/ethnicity, infant birth weight, gestational age, and gender. At 4 months of age, 90% specificity for HIV diagnosis was associated with 60% sensitivity. For ease of use, graphical estimates based on cubic splines for the time-dependent parameters in a Box-Cox transformation (L), the median (M), and the coefficient of variation (S) were used to create LMS centile curves to show the sensitivity and specificity of CD4+/CD8+ T cell ratios in HIV-infected and uninfected infants until 12 months of age. At 6 months of age, a simplified equation that incorporated sequential CD4+/CD8+ T cell ratios and hematocrit values resulted in improved receiver operating characteristic curves, with 94% positive predictive value and 98% negative predictive value. The positive and negative predictive values remained above 90% in simulated infant populations over a wide range of HIV infection prevalence values. CONCLUSIONS. In the absence of virological diagnosis, a presumptive diagnosis of HIV infection status can be made on the basis of CD4+/CD8+ T cell ratios in HIV-1-exposed infants after 2 months of age; sensitivity and specificity can be improved at 6 months by using a discriminant analysis equation.