Challenges in the treatment of HIV-1 infected children with highly active antiretroviral therapy

Nobody could have predicted the tremendous implications of the headline in The New York Times of July 5, 1981: "Rare cancer in homosexuals". This article contained the first description of the disease "Acquired Immune Deficiency Syndrome" (AIDS) and marked the beginning of a pandemic by the Human Immunodeficiency Virus (HIV). (1) Three years after the first adults with AIDS were identified, similar disease features were reported in children. (2, 3) In general, HIV infection progresses more rapidly in children than in adults. This progression is associated with a higher viral burden, a more rapid depletion of CD4+ T-cell lymphocytes and impaired growth characteristics. (4- 8) HN infected children may be divided in three groups on the basis of disease progression: "rapid progressors" (±20%), "intermediate progressors" (±60%) and "slow progressors" (±20%). (9-12) The first group shows a rapid decrease in CD4+ T-cells and develops AIDS (CDC classification C (13)) within the first two years of life. In "intermediate progressors" a more gradual decrease in CD4+ T-cell counts is observed. These children don't have symptoms of serious immunosuppression until the age of 7-8 years. The "slow progressors" are asymptomatic at the age of 8 years and have a normal or slightly decreased CD4+ T-cell count. Symptoms associated with HIV infection in infants and children are dependent on the extent of immunosuppression. The Centers for Disease Control and Prevention have developed a pediatric classification system based on the seriousness of symptoms. (13) In children with intermediate and slow progression rates an asymptomatic medical history may be present possibly in combination with a slightly increased incidence of bacterial infections and lymphadenopathy. Pneumocystis carinii pneumonia (PCP) was the most frequently occurring opportunistic infection in HIV infected children during the initial period when HIV exposed and HN infected children in Europe and the USA did not routinely receive PeP-prophylaxis.

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