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

• Published in: Pediatrics (Evanston) 2008-08, Vol.122 (2), p.331-339
• Main Authors: Pahwa, Savita, Read, Jennifer S, Yin, Wanrong, Matthews, Yvonne, Shearer, William, Diaz, Clemente, Rich, Kenneth, Mendez, Hermann, Thompson, Bruce, Women and Infants Transmission Study
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Babies; Biological and medical sciences; Biomarkers - blood; Case-Control Studies; CD8-Positive T-Lymphocytes - immunology; Cohort Studies; Diagnosis; Disease transmission; Female; Follow-Up Studies; General aspects; HIV; HIV infection in children; HIV Infections - diagnosis; HIV Infections - epidemiology; HIV Infections - transmission; HIV Seropositivity; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Incidence; Infant, Newborn; Infections; Infectious Disease Transmission, Vertical - statistics & numerical data; Infectious diseases; Male; Medical diagnosis; Medical sciences; Multivariate Analysis; Pediatric HIV infections; Pediatrics; Perinatal infection; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Infectious - diagnosis; Pregnancy Complications, Infectious - epidemiology; Probability; Prospective Studies; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Sex Distribution; Studies; T cell receptors; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0031-4005; 1098-4275
• DOI: 10.1542/peds.2007-2308

In this study, we tested the hypothesis that the CD4(+)/CD8(+) T cell ratio could predict HIV infection status in HIV-exposed infants. 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. 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. 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.