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Human immunodeficiency virus infection in children: nature of immunodeficiency, clinical spectrum and management

The causative agent of acquired immunodeficiency syndrome is a retrovirus, human T lymphotropic virus type III/lymphadenopathy-associated virus, now known as human immunodeficiency virus (HIV). Infection of children with HIV results in a wide spectrum of clinical manifestations, ranging from asymptomatic to symptomatic, with the “severest disease forms including neurologic deterioration, opportunistic infections and malignancy. This virus infects preferentially T cells bearing the CD4 receptors and also seems to exhibit preference for the central nervous system. The predominant route of infection in children is transplacental, and most affected children are infected at the time of birth. For women who give birth to infants with congenital infection with HIV, the main risk factor is intravenous drug abuse; a smaller percentage of these women acquire the infection via sexual contact and a few are infected via blood transfusions. Estimates for the incidence of transmission of the virus from an infected mother to her offspring vary from about 20 to 70%. Infection in most children and adults is documented by serologic testing, inasmuch as almost all infected people are HIV antibody-positive. Mothers of congenitally affected children are always HIV antibody-positive and also frequently have immune abnormalities. Women who give birth to infected children may, however, be asymptomatic in 50% of instances or more. Because antibodies to HIV are predominantly of the IgG class, they cross the placenta. All infants born to infected women therefore acquire passively transferred antibodies to HIV irrespective of whether or not the infants are infected with the virus itself. These passively transferred antibodies may sometimes persist for as long as 15 months. Thus in infants and children under 15 months of age in the absence of symptoms, the only definitive way to establish diagnosis is by viral isolation or viral antigen detection. Clinically the HIV-infected children can be divided into two groups, symptomatic and asymptomatic. Among the symptomatic group the main diagnostic specific features are: (1) opportunistic infection, e.g. with Pneumocystis carinii pneumonia; (2) interstitial pneumonitis with respiratory distress resulting from lymphocytic interstitial pneumonitis; (3) microcephaly and other neurologic abnormalities; (4) recurrent bacterial infections. Other common but nonspecific features include generalized lymphadenopathy, hepatomegaly, splenomegaly, diarrhea, failure to thrive, fever and parotitis. The ever widening clinical spectrum of pediatric HIV infection has led to a reevaluation of terms like acquired immunodeficiency syndrome and acquired immunodeficiency syndrome-related complex; this entity is now more appropriately discussed under the broad perspective of HIV infection. A new provisional classification system has been developed by the Centers for Disease Control which takes into consideration the majority of the clinical features associated with HIV infection. Immunologie findings include marked hyper-gammaglobulinemia with elevations in IgG, with or without elevations in IgA and IgM, depletion of T4 subset of T cells and reversal of T4/T8 ratio to <1. The spectrum of immunologie aberrations associated with pediatric HIV infection has also widened. Recently we have begun to recognize severe hypogammaglobulinemia as a feature of immunodeficiency in some HIV-infected infants, more commonly if they are of premature birth. Such children frequently have associated intracranial calcifications. The HIV antibody test might be negative in such children, and specific virologie isolation is required to establish the diagnosis. Immunologie responses to HIV and mechanisms involved in immunologie dysfunction associated with HIV-infected states are under intense investigation as are approaches to vaccination and therapy. Discovery of other human and simian retroviruses has heightened our awareness of the potential link between viruses and human diseases with as yet unexplained etiology.