Transmission of HIV-1 from infected mothers to the fetus or newborn occurs with a frequency of 13-45%. TWO patterns of infection consistent with in utero or intraoartum transmission have been demonstrated. Demonstration of virus in cord blood and subsequent samples suggest in utero infection. Negative viral isolation and PCR studies on cord blood and early neonatal specimens with subsequent detection of viremia by 1 2 weeks of age is consistent with late in utero or intrapartum infection. Ten children were identified as infected, all within the first 8 weeks of life. Evidence of infection was found in cord blood or subsequent samples from 4 infected children, consistent with in utero infection. Virologic studies on cord blood and early neonatal specimens from the 6 other infected children were negative but became positive by 8 weeks of age, consistent with either late in utero or intrapartum transmission.
Evidence of viral replication consistent with primary viremia was observed between 3 and 1 2 weeks of age. This viremia resolved in the absence of antiretroviral therapy and in the absence of circulating HIV-1-specific CTL or broadly neutralizing antibodies. Following acute infection, there is a progressive immune attrition with loss of CD4 T helper cells.
Circulating virus specific cytotoxic T cells are not demonstrable in the majority of infants during the course of disease progression. Deficient imune responses following primary infection may explain the more rapid onset of symptomatic disease following vertical HIV infection.
QZ 002ROLE OF HIV-1 INFECTION OF THYMOCYTES IN THE PATHOGENESIS OF PEDIATFX AIDS. Christel H. Uittenbogaart, Deborah
HIV infection leads to a decline in CD4' T cell numbers and is characterized by an impaired cellular immune function resulting in the development of AIDS. However, a functional defect in the cellular immune system is detectable early in HIV infection. at a time when numbers of CD4' T cells are within the normal range The thymus is essential for normal T cell development and is particularly active during fetal and neonatal life. The great potential of the thymus to generate mature T cells before and after birth may explain the initial lack of low CD4' T cells in HIV-infected children Thymic abnormalities have been reported in fetuses aborted from HIV seropositive women. Therefore, we studied the effect of HIV infection on human thymocyte maturation in-vitro and in-vivo in the SClD mouse model. Since thymocytes can be infected \villi I IIV, we investi::nted which cytokines were involved in augiiicntitig I1IV production Thymocytes were infected with clinical isolates. JR-CSF or JR-FL, and cultured in serum-free medium in the presence of the cytokines 1L-2, IL-4 and IL-7 (alone or in combination). Previously, we have shown that IL-2 is a growth factor for mature thymocytes, while IL-4 and 1L-7 are differentiation factors for immature thymocytes We found that after 10-14 days of culture, both IL-4 and 1L-7 promote the appearance of large thymocytes with a mature phenotype. Mature cells express high density ("bright") CD3, "bright" CD4 and/or CD8 and "bright" CD45RA. Our results show that IL-2