Published online August 1, 2008
PEDIATRICS Vol. 122 No. 2 August 2008, pp. 331-339 (doi:10.1542/10.1542/peds.2007-2308)

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ARTICLE

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

Savita Pahwa, MD^a, Jennifer S. Read, MD^b, Wanrong Yin, MS^c, Yvonne Matthews, MA^c, William Shearer, MD^d, Clemente Diaz, MD^e, Kenneth Rich, MD^f, Hermann Mendez, MD^g, Bruce Thompson, PhD^c for the Women and Infants Transmission Study

^a Departments of Microbiology and Immunology, and Pediatrics, University of Miami, Miller School of Medicine, Miami, Florida
^b Pediatric, Adolescent, and Maternal AIDS Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
^c Clinical Trials & Surveys Corp, Baltimore, Maryland
^d Department of Pediatrics, Baylor College of Medicine, Houston, Texas
^e Department of Pediatrics, University of Puerto Rico, San Juan, Puerto Rico
^f Department of Pediatrics, University of Illinois at Chicago, Chicago, Illinois
^g Department of Pediatrics, State University of New York, Brooklyn, New York

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.

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Key Words: HIV diagnosis • perinatal HIV transmission • HIV-exposed infants • CD4⁺/CD8⁺ T cell ratio

Abbreviations: MTCT—mother-to-child transmission • LMS—least-mean squares • PCR—polymerase chain reaction • ROC—receiver operating characteristic • WITS—Women and Infants Transmission Study

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Accepted Dec 12, 2007.

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