Since the initial descriptions in 1981 of cases of a rare disease, Pneumocystis carinii pneumonia, among homosexual men in Los Angeles, AIDS has expanded to become a global pandemic. In the past two decades, millions of people worldwide have died of AIDS, and one in every 200 Americans is infected with HIV-1 (UNAIDS, 2000). Our concept of the biology of HIV infection has changed radically to a model of continuous active HIV replication throughout HIV infection (Ho et al., 1995). The introduction of highly active antiretroviral therapy (HAART) regimens in the mid-1990s has resulted in a 50% decline in AIDS death rate, decreased maternal–infant transmission rates, reductions in incidence rates of opportunistic infections (Fig. 103.1), and a 40–50% decrease in the incidence of HIV-associated dementia (Brodt et al., 1997). Nonetheless, AIDS-associated neurological diseases continue to be major causes of morbidity and mortality, and because the blood–brain barrier may prevent the CNS penetration of antiretroviral agents, the brain may serve as a sanctuary for HIV, with persistent HIV replication within macrophages and microglia, the principal target cells in the CNS.
Epidemiology of HIV infection and AIDS
The World Health Organization (WHO) estimates that worldwide there have been 13.9 million deaths from AIDS and the number of infected people reached 54 million in 2000 (UNAIDS Joint United Nations Programme on HIV/AIDS, 1998) with 16000 new infections occurring each day. In the USA, through June 1999, surveillance has identified 711344 cases of AIDS and 420201 AIDS deaths (Centers for Disease Control and Prevention, 1999) and 431924 Americans are estimated to be living with HIV/AIDS. The proportion of AIDS cases among women has increased from 8 to 23% with proportional decreases among homosexual men. Though the disease was first recognized in the USA among homosexual men and injection drug users, heterosexual contact now constitutes the most frequent risk factor worldwide. In developed countries, in utero transmission from mother to infant has been significantly reduced through the use of antiretrovirals during pregnancy (Connor et al., 1994). Blood products are now an infrequent source of HIV infection in the USA, with the risk of HIV infection estimated at 1 in 493000 units of blood (Schreiber et al., 1996).