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PATHOGENESIS & EPIDEMIOLOGY

Pathogenesis & Transmission

Human immunodeficiency virus (HIV) is a retrovirus that enters and then integrates its nucleic acid into the DNA of cells of the immune system, including helper T lymphocytes (CD4 T lymphocytes), monocytes, and macrophages. The function and number of CD4 T lymphocytes and other affected cells are diminished by HIV infection, resulting in profound defects in cell-mediated and humoral immunity. HIV is found in blood, semen, preseminal fluids, rectal fluids, vaginal fluids, and breast milk, with transmission occurring via sexual contact, sharing contaminated needles, and perinatal transmission (in utero, peripartum, breast-feeding). Rarely, infants have acquired HIV from food premasticated by a person with HIV. Casual, classroom, or household contact with an HIV-infected person poses no risk of transmission in the absence of contact with blood or bloody secretions. Exposure resulting from accidental needle sticks or, rarely, mucosal exposure to blood may occur, mainly in health care settings.

At the time of exposure, HIV migrates to regional lymph nodes, replicates, and spreads to lymphoid tissues throughout the body. Based on nonhuman primate models, replicating virus is disseminated by 48 hours postinfection. Approximately 2 weeks after exposure, a high level of virus is detected in the bloodstream. In adults without therapy, the level of viremia declines concurrent with the appearance of an HIV-specific host immune response, and plasma viremia usually reaches a steady-state level about 6 months after primary infection. An asymptomatic period usually follows, lasting from 1 year to more than 12 years. However, ongoing viremia and immune activation causes injury to the immune system and other organs.

Infants with perinatal HIV infection have viremia that rises steeply after birth, reaching a peak at 1–2 months of age. In contrast with adults, infants have a gradual decline in plasma viremia that extends to age 4–5 years. Without treatment, up to 50% of infants will have rapid disease progression to AIDS or death by age 2 years.

HIV infection, in the absence of treatment, causes progressive immune incompetence with the hallmark loss of CD4 T-lymphocyte numbers, leading to conditions that meet the definition of acquired immunodeficiency syndrome (AIDS) and, eventually, death. AIDS is diagnosed when an HIV-infected individual develops any of the stage 3 opportunistic illnesses or other conditions listed in Table 41–1. In adults and children older than 6 years, the criteria for a diagnosis of AIDS also include an absolute CD4 T-lymphocyte count of 200 cells/μL or less.

Table 41–1.HIV-related symptoms in children.

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