Human immunodeficiency virus (HIV) infection results in a wide array of Clinical Manifestations and varied natural history. HIV type 1 (HIV-1) is much more common in the United States than is HIV type 2 (HIV-2). This chapter, therefore, addresses HIV-1 infection, unless otherwise specified. Acquired immunodeficiency syndrome (AIDS) is the name given to the most advanced stage of HIV-1 infection. The Centers for Disease Control and Prevention (CDC) has devised a case definition that comprises AIDS-defining conditions that are used for surveillance (Table 3.24). The CDC classifies all infected children younger than 13 years of age by varying degrees of clinical expression of disease (Table 3.25) and immunologic status (Table 3.26).¹,² This pediatric classification system emphasizes the importance of the CD4+ T-lymphocyte count and percentage as critical immunologic parameters and as markers of prognosis. Data regarding plasma HIV-1 RNA concentration (viral load) are not included in this classification.

Table 3-24

Table 3-25

Table 3-26

Early manifestations of pediatric HIV infection include unexplained fevers, generalized lymphadenopathy, hepatomegaly, splenomegaly, failure to thrive, persistent or recurrent oral and diaper candidiasis, recurrent diarrhea, parotitis, hepatitis, central nervous system (CNS) disease (eg, hyperreflexia, hypertonia, floppiness, developmental delay), lymphoid interstitial pneumonia, recurrent invasive bacterial infections, and other opportunistic infections (eg, viral and fungal).¹ With timely diagnostic testing and appropriate Treatment, Clinical Manifestations of HIV-1 and occurrence of AIDS-defining illnesses are rare among children in industrialized nations.

The frequency of infections attributable to different opportunistic pathogens in the era before highly active antiretroviral therapy (HAART) varied by age, pathogen, previous infection history, and immunologic status. In the pre-HAART era, the most common opportunistic infections observed among children in the United States were infections caused by invasive encapsulated bacteria, Pneumocystis jirovecii (previously known as Pneumocystis carinii ), varicella-zoster virus, cytomegalovirus, herpes simplex virus, Mycobacterium avium complex (MAC), and Candida species. Less commonly observed opportunistic pathogens included Epstein-Barr virus, Mycobacterium tuberculosis, Cryptosporidium species, Isospora species, other enteric pathogens, Aspergillus species, and Toxoplasma gondii . In the HAART era, there has been a substantial decrease in frequency of all opportunistic infections.

Malignant neoplasms in children with HIV-1 infection are relatively uncommon, but leiomyosarcomas and non-Hodgkin B-cell lymphomas of the Burkitt type (including some that arise in the CNS), occur more commonly in children with HIV-1 infection than in immunocompetent children. Kaposi sarcoma is rare in children in the United States.

Development of an opportunistic infection, particularly P jirovecii pneumonia (PCP), progressive neurologic disease, and severe wasting, are associated with a poor prognosis. In the absence of Treatment, prognosis for survival also is poor in infants who were infected perinatally and who have high viral loads (ie, greater than 100 000 copies/mL), markedly decreased CD4+ T-lymphocyte counts (see Table 3.27, for age-specific CD+ T-lymphocyte count ranges) and percentages (less than 15%), and symptoms developing during the first 6 months of life. When HAART regimens are begun early, prognosis and survival rates improve dramatically. Although median survival to 9 years of age was reported before more potent combinations of antiretroviral (ARV) drugs became available, recent studies in the United States and Europe show greater than 95% survival to 16 years of age or older and preservation of reasonable immune system function, especially in children and adolescents who adhere to their medical regimens.

Table 3-27