Worldwide, 1 million of the 7 million people with acquired immunodeficiency syndrome (AIDS) are children and adolescents and 2 million children and adolescents have died from AIDS, with 90% of those infected living in developing nations. Half of the approximately 6 million infections diagnosed worldwide annually occur among people 15 to 24 years of age; approximately 25% of the 40,000 new infections per year in the United States occur in people 13 to 21 years of age. In the United States, mortality from human immunodeficiency virus (HIV) infection and AIDS has decreased in people under 24 years of age, but the hopes presented by new treatments and preventive efforts have been darkened by the continuous increase in risk reported among American youth.¹,²,³

Pediatric AIDS is seen disproportionately among children of color. Of the 3,788 children under the age of 13 living with AIDS in 2003, 570 were non-Hispanic White, 2,461 were African American, 853 were Hispanic/Latino, 17 were Asian-American, and 10 were American Indian. The children that run the highest risk of infection from HIV-infected mothers are infants born to mothers who are prostitutes or intravenous drug users (IDUs); mothers whose sexual partners are bisexual, have hemophilia, or abuse drugs; infants with a history of blood transfusions; and infants who have hemophilia. Children can also become infected with HIV through exposure to nonsterilized needles, or by breast feeding from an infected mother. Most cases among children and youth in the United States occur in the coastal states and large urban areas. Socioeconomic and cultural factors among Latino and African-American populations, such as poverty, high drug use, and sexual lifestyles are also factors in the prevalence of AIDS among their descendants.¹,²,³

Based on current trends, a young person aged 13 to 21 years is infected with the HIV virus in the United States every hour of every day. HIV spreads sexually among the adolescent population more than in any other group. Adolescents who are homosexual or use drugs, youthful offenders who drop out of school or run away from home, and immigrant youth are especially vulnerable to HIV infection. These youth are frequently difficult to reach through prevention and education efforts and have limited access to medical insurance. The African- American and Latino populations are disproportionately represented amongst adolescents contracting HIV infection, accounting for over 85% of AIDS cases in 2002. Adolescent
females also represent a higher proportion of new HIV and AIDS cases, with 50% of new cases between ages 13 and 19, compared in 2002, and 66% of adolescent females infected in heterosexual encounters. School dropouts constitute approximately 3 million adolescents in the United States (12.7%) and are primarily youth of color. This group of youth has a high frequency of behaviors (particularly unprotected sexual activity and intravenous drug use) that place them at risk for contracting HIV or some other sexually transmitted disease and have the least accessibility to prevention programs.¹,²,³

AIDS is the seventh leading cause of death among children from 1 to 4 years of age and the sixth main cause of death between ages 15 and 24 years in the United States. The first children infected with HIV were described in 1983. From that beginning, the global epidemic of HIV has had a deep impact on the health of children and their survival. At least all the infections of HIV among young children are due to vertical transmission, which can occur in utero, intrapartum (through exposure to maternal blood products or transfusions), or postpartum through breast feeding. Detection during the interpartum period with more sophisticated screening and diagnostic tests provides a crucial opportunity for prevention. Transmission after childbirth through the mother contributes about a third to half of the world’s vertical transmission, which can be prevented with timely maternal treatment with retrovirals. In the absence of maternal antiretroviral treatment, the risk of HIV infection among infants is approximately 25% (ranging from 10% in European studies to 45% in African studies), but can go down to 4% to 8% with maternal and infant antiretroviral treatment. Carefully designed studies of the epidemic are clarifying immunologic, virologic, genetic, and behavioral factors that affect the risk of transmission of HIV from the mother to the infant, as well as response to antiretrovirals, and the natural history of the HIV infection in prenatally infected children.¹ Major advances in pediatric AIDS, however, have been the dramatic decrease in the number of new cases under the age of 13 (from 952 in 1992 to 50 in 2003), as well as the decrease in mortality from HIV disease and AIDS in both the under-13 and 14- to 24-year age-groups in the United States. This has been the result of perinatal maternal testing and of more effective antiretroviral therapies.³

A major remaining challenge is the translation of these advances to poorer, underserved populations and Third World regions of the world. One geographic area that has not received much attention related to the HIV/AIDS epidemic is Latin America. Given its proximity to the United States and its contribution to immigration, particularly of young immigrants, it merits much closer attention. The Pan American Health Organization reports that today there is probably a higher rate of HIV infection in Latin America than in the United States. As of 1997, approximately 470,000 people have died of AIDS in the hemisphere, with 90,000 orphans resulting in Latin America alone, but these figures are considered underestimates. Among the 812,000 cases reported in the hemisphere, all but 14,000 are pediatric cases. Among the 22.6 million people worldwide that are considered living with HIV disease or AIDS, 1.6 millions live in the Latin American and Caribbean region. Unless prevention programs are refocused on these affected groups, the HIV virus could become the main cause of death among youth in Latin America and the Caribbean.⁴

Providing care to these populations, to patients and their families in these countries, is an enormous task given the limited resources of developing nations. Additionally, the lower socioeconomic status of women and children substantially limits the effectiveness of programs for care and prevention in developing nations.⁴

Among children, HIV penetrates early into the central nervous system (CNS) during the course of the illness. Abnormalities of the CNS are significant and frequent complications of AIDS in infants and children. Although their causes can be related to HIV infection, malnutrition and
poor prenatal and postnatal care can also contribute significantly to such problems. Other factors that affect the neuropsychological function of seropositive children include prenatal insults and other diseases, such as other infections, strokes, and neoplasms.¹

Neurocognitive deterioration appears to be associated with the increased replication of the HIV virus, resulting in HIV-associated progressive encephalopathy (HIV-PE). HIV-PE is associated with a triad of symptoms: impaired brain growth, progressive motor dysfunction, and loss or plateauing of developmental milestones. HIV-PE has an estimated prevalence of 13% to 23% among infected children. The course of HIV-PE in infants or young children is determined by its timing in the child’s brain development, the strain of HIV, and genetic vulnerabilities. Three patterns of abnormal neurocognitive development have been described with HIV-PE: rapid HIV-PE with loss of attained milestones, subacute progression of encephalopathy with relatively stable periods, and static encephalopathy with failure to achieve new milestones. Longitudinal assessments allow the differentiation between HIV-PE and mental retardation resulting from other factors, such as maternal drug addiction and poor prenatal care. There is no obvious correlation between immunologic status and the development of HIV-PE.⁵,⁶

Autopsy studies on patients with HIV-PE reveal decreased brain weight, inflammatory changes, calcifications of basal ganglia vessels, white matter deterioration, and astrocytosis.⁶ Proposed mechanisms for the pathogenesis of HIV disease in the CNS include direct neuronal injury, macrophage destruction resulting in neurotoxicity, dysfunction caused by viral products, neuroreceptor blockade, coinfection with other agents, autoimmune reactions, antibody- mediated cellular toxicity, integration of the provirus in CNS cell lines, alteration of the blood–brain barrier, and brain vascular changes.⁵,⁶ High frequencies of vascular lesions, ranging from aneurysms to infarctions, have been found using neuroimaging studies.⁷ The overall computed tomography (CT) brain scan severity rating and the level of the neurotoxin quinolinic acid in the cerebrospinal fluid have been found to be highly predictive of the level of cognitive functioning and impairment in children.⁸

Among children, the deterioration of language skills commonly occurs with HIV infections, particularly expressive more than receptive language. The periodic evaluation of language development should be part of the regular monitoring of infants and children with HIV infection as a method of evaluating the progression of the illness and the effectiveness of prescribed treatment. Visual-spatial and visual-motor skills are cognitive functions sensitive to the stage of the illness, method of transmission, and the environment in which the child lives.⁵ In one recent study, HIV-infected patients and control children had similar performance on a panel of neuropsychological tests except for spatial learning and memory using the Children’s Memory Scale total score. Choline levels in the hippocampus correlated positively with the delayed spatial memory tests in the patients, but not in the controls.⁹ Learning disabilities associated with cognitive impairment can be seen in elementary school–age children infected with HIV, which can be associated with gradual diminution in their mental function because of the disruption of cortical or subcortical structures.¹⁰

The use of the retroviral medications can moderate some of the functional difficulties faced by these children and improve cognitive deficits, at least for a period of time. There is greater efficacy of retroviral treatment associated with greater brain impairment before treatment and better CNS penetration of the antiretroviral agent. However, the effect of retroviral treatment has not been sustained in many children beyond 6 months of treatment, with cognitive decline in the face of virologic and immunologic improvement, though recent advances have been made in this area. Specific neuropathologic and neuropsychological deficits are probably permanent, and there are limitations posed by the mechanisms of action of retroviral treatment (resulting in mutations and viral resistance), as well as interactions amongst multiple drugs.¹,¹¹