Natural history of primary Epstein-Barr virus infection in children of mothers infected with human immunodeficiency virus type 1

Abstract

The natural history of Epstein-Barr virus (EBV) infection in 556 infants born to 517 human immunodeficiency virus (HIV) type 1-infected mothers was studied in a prospective, multicenter, cohort study. HIV-1-infected children had a cumulative EBV infection rate similar to HIV-1-uninfected children at age 3 years (77.8% vs. 84. 9%) but had more frequent oropharyngeal EBV shedding (50.4% vs. 28. 2%; P<.001). The probability of shedding decreased with longer time from EBV seroconversion and was similar to that of HIV-1-uninfected children 3 years after seroconversion. HIV-1-infected children identified as rapid progressors shed EBV more frequently than nonrapid progressors (69.4% vs.41.0%; P=.01). HIV-1-infected children with EBV infection had higher mean CD8 cell counts. EBV infection did not have an independent effect on mean CD4 cell counts, percent CD4, IgG levels, HIV-1 RNA levels, lymphadenopathy, hepatomegaly, or splenomegaly. Early EBV infection is common in children born to HIV-1-infected mothers. Children with rapidly progressive HIV-1 disease have more frequent EBV shedding.

Figures

Figure 1

Cumulative rates (and 95% confidence intervals) of (A) Epstein-Barr virus (EBV) infection (defined as youngest age of either first oropharyngeal shedding or age at EBV seroconversion) and (B) EBV seroconversion alone of human immunodeficiency virus type 1 (HIV-1)–infected and –uninfected children for first 3 years of life born to HIV-1–infected mothers.

Figure 2

Cumulative rates (and 95% confidence intervals) of (A) Epstein-Barr virus (EBV) infection (defined as youngest age of either first oropharyngeal shedding or age at EBV seroconversion) and (B) EBV seroconversion alone of human immunodeficiency virus type 1–infected children identified as rapid progressors or as nonrapid progressors for first 3 years of life.

Figure 3

Model-based estimates (and 95% confidence intervals) of oropharyngeal Epstein-Barr virus (EBV) shedding by age of human immunodeficiency virus type 1 (HIV-1)–infected rapid progressors (RP; n = 17; 59 samples), HIV-1–infected nonrapid progressors (non-RP; n = 33; 121 samples), and HIV-1–uninfected (n = 195; 579 samples) EBV-seropositive children. Significant differences overall in oropharyngeal shedding were found between HIV-1–infected children (50.4% overall) vs. HIV-1–uninfected children (28.2% overall; P < .001), RP (69.4% overall) vs. non-RP (40.9% overall; P = .01), RP vs. HIV-1–uninfected children (P < .001), and non-RP vs. HIV-1–uninfected children (P = .05).

Figure 4

Model-based estimates (and 95% confidence intervals [CIs]) of probability of oropharyngeal Epstein-Barr virus (EBV) shedding for 3 years after EBV seroconversion of human immunodeficiency virus type 1 (HIV-1)–infected (n = 36) and HIV-1–uninfected children (n = 108) born to HIV-1–infected mothers. No. of children at each time point is indicated.

Figure 5

Model-based means (and 95% confidence intervals) for (A) CD4 and (B) CD8 cells/mm3 (n = 76 human immunodeficiency virus type 1 (HIV-1)–infected and n = 311 HIV-1–uninfected children), (C) IgG levels (mg/dL; n = 69 HIV-1–infected and n = 266 HIV-1–uninfected children), and (D) serum log10 HIV-1 RNA levels (HIV-1 RNA genome copies/mL; n = 67 HIV-1–infected children) by age according to HIV-1 infection status and Epstein-Barr virus infection status at each age. Means for CD4 and CD8 cell counts are cube-root transformations; IgG level is a geometric mean.