Immunologic targets of HIV infection: T cells. NICHD IVIG Clinical Trial Group, and the NHLBI P2C2 Pediatric Pulmonary and Cardiac Complications of HIV Infection Study Group.

One of the principal targets of HIV infection is the human peripheral blood CD4+ T cell, resulting in progressive CD4+ lymphocyte loss. Hypothesized mechanisms for this loss include apoptosis, cytolytic reactions, V-beta gene deletion of the T-cell receptor (TCR) by superantigens, CD4+ lymphocyte syncytium formation, and autoimmune reactions. In adults with HIV infection, the critical decline in CD4+ lymphocyte number that heralds the onset of AIDS-defining conditions is well characterized, whereas in infants and children the critical level of CD4+ cells predisposing to the development of AIDS-defining conditions or mortality is not fully characterized, due to an incomplete knowledge of CD4+ lymphocyte number and changes with age in normal and HIV-infected children. In a prospective study of 317 infants born to HIV-infected women, early results show that the monthly change in absolute CD4+ lymphocyte number over a 3- to 9-month period in HIV-infected infants was -109 cells/mm3 per month, at least double the rate of decline measured in HIV-noninfected infants in the study or that calculated from normal infants' values reported in the literature. In other clinical studies in HIV-infected infants and children, it was possible to study the effect of low CD4+ cell counts on clinical status and mortality. In HIV-infected pediatric patients younger than 1 year, it was possible to correlate low CD4+ cell number with advanced disease status (CDC pediatric class P-2). It was also possible to correlate extremely low CD4+ cell counts (< 200 cells/mm3) in HIV-infected children with a significant risk of mortality within the next 3 months of life. Sequential CD4+ cell analysis of HIV-high-risk infants will delineate the rate of HIV-related decline in CD4+ cells, thus facilitating the diagnosis of HIV infection and aiding in identification of HIV-infected children at high risk of disease progression or death.

Duke Scholars

Author Thomas Norton Denny Medicine, Duke Human Vaccine Institute