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The introduction of highly active antiretroviral therapy (HAART), with either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor in combination with two or more nucleoside reverse transcriptase inhibitors, was a landmark event in the history of HIV treatment. Since 1996, HAART has been widely adopted in the USA and Western Europe, with profound impact on HIV-related morbidity and mortality1,2,3,4,5,6. In April 2001, fifteen antiretroviral drugs had been licensed for use in Europe and the USA and an additional eight were in development. In Europe, the USA and Canada, the mortality of AIDS (Figure 1) and the incidence of different AIDS-defining illnesses (Figure 2) have declined over the past decade. In the UK, new AIDS diagnoses dropped from 1187 in 1994 to 507 in 1999, the decline being steepest between 1996 and 1998 (from 941 to 522) and greatest in those infected through sex with men1. The biggest percentage reductions in incidence of AIDS diagnoses occurred with Pneumocystis carinii pneumonia (PCP) (35-80%), Kaposi's sarcoma (34-75%), cryptosporidiosis (60-88%), oesophageal candidiasis (29-81%) and cytomegalovirus (CMV) (70%)2,3,4,5,6, and discontinuation of primary and even secondary prophylaxis has proved possible for several of these infections7. The use of HAART has also been associated with remission of Kaposi's sarcoma, refractory cryptosporidiosis, and progressive multifocal leukoencephalopathy, in addition to improvement in many of the common HIV-related symptoms such as night sweats, fatigue, weight loss, and seborrhoeic dermatitis. Some unusual manifestations of infections have been reported as a result of the heightened immune response or immune reconstitution associated with antiretroviral therapy. These include lymphadenitis due to Mycobacterium avium complex, vitritis associated with CMV, flare-up of hepatitis due to hepatitis B, and an aggressive course of multicentric Castleman's disease associated with human herpesvirus-8. Figure 1 Impact of protease inhibitor use on mortality. Reproduced by permission from Palella et al. (Ref. 3) Figure 2 Annual events of different AIDS-defining diseases calculated as events per 100 patient-years. Reproduced by permission from Brodt et al. (Ref. 2). PML=progressive multifocal leucoencephalopathy The spectrum of paediatric HIV disease has also changed dramatically—not only because of the availability of HAART but also because of prompt early diagnosis and treatment and the development of more reliable surrogate markers of disease progression. In addition, because of a widespread increase in screening of pregnant women for HIV, more patients are identified as HIV-infected and receive antiretroviral therapy during pregnancy. This in turn has resulted in a sharp decline in the prevalence of childhood infection in developed countries. Since 1994 in various parts of Western Europe, mother-to-child HIV transmission rates have decreased from 25% to less than 8%.
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Easterbrook et al. (2001) studied this question.
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