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. 2008 Aug;122(2):331-9.
doi: 10.1542/peds.2007-2308.

CD4+/CD8+ T cell ratio for diagnosis of HIV-1 infection in infants: Women and Infants Transmission Study

Savita Pahwa  1 , Jennifer S Read, Wanrong Yin, Yvonne Matthews, William Shearer, Clemente Diaz, Kenneth Rich, Hermann Mendez, Bruce Thompson; Women and Infants Transmission Study
Collaborators, Affiliations

CD4+/CD8+ T cell ratio for diagnosis of HIV-1 infection in infants: Women and Infants Transmission Study

Savita Pahwa et al. Pediatrics. 2008 Aug.

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.

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Figures

Figure 1
Figure 1
Derivation of the Study Population and Median CD4/CD8 Ratios at Each Study Visit
Figure 2
Figure 2
ROC Plot of CD4% vs. CD4/CD8 (Univariate Analyses)
Figure 3
Figure 3
ROC Plot of CD4% vs. CD4/CD8 (Adjusted for Other Covariates)
Figure 4
Figure 4
Reference Centile Curves for CD4/CD8 by HIV-1 Infection Status: 5th, 10th, 25th, Median, 75th, 90th and 95th Percentiles
Figure 5
Figure 5
a. Mean of CD4/CD8 ratio and b. Mean of hematocrit by age in HIV-1-infected and HIV-1-uninfected infants whose mothers did or did not receive antepartum or intrapartum antiretroviral drugs (ARVs)
Figure 6
Figure 6
PPV and NPV based on discriminant function for simulated data with various prevalences of HIV-1 infection among Infants. * Indicates number and proportion of children who could be classified using CD4/CD8 ratio and hematocrit measurements
See this image and copyright information in PMC

References

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