Disseminated bacterial infection with nontuberculous, or atypical, mycobacteria (mainly Mycobacterium aviumintracellulare) also occurs late, in the setting of severe immunosuppression. Coincident with the AIDS epidemic, the incidence of tuberculosis has risen dramatically. Worldwide, almost one third of all deaths in AIDS patients are attributable to tuberculosis, but this compli cation remains uncommon in the United States. Both reactivation of latent pulmonary disease and new primary infection contribute to this toll. As with tuberculosis in other settings, the infection may be confined to lungs or may involve multiple organs. Most worrisome are reports indicating that a growing number of isolates are resistant to multiple anti-mycobacterial drugs.
Cryptococcosis occurs in about 10% of AIDS patients. As in other settings with immunosuppression, meningitis is the major clinical manifestation of cryptococcosis. Toxoplasma gondii, another frequent invader of the CNS in AIDS, causes encephalitis and is responsible for 50% of all mass lesions in the CNS.
JC virus, a human papovavirus, is another important cause of CNS infections in HIV-infected patients. It causes progressive multifocal leukoencephalopathy (Chapter 23). Herpes simplex virus infection is manifested by mucocutaneous ulcerations involving the mouth, esophagus, external genitalia, and perianal region. Persistent diarrhea, which is common in untreated patients with advanced AIDS, is often caused by infections with protozoans or enteric bacteria.
Patients with AIDS have a high incidence of certain tumors, notably Kaposi sarcoma, B cell lymphoma, cervical cancer in women, and anal cancer in men. These tumors are often considered AIDS-defining malignancies. It is estimated that 25% to 40% of untreated HIV-infected individuals will eventually develop a malignancy. Many of these tumors are caused by oncogenic DNA viruses, including Kaposi sarcoma herpesvirus (Kaposi sarcoma), EBV (B cell lymphoma), and human papillomavirus (cervical and anal carcinoma). These viruses establish latent infections that are kept in check in healthy individuals by a competent immune system. The increased risk for malignancy in AIDS patients exists mainly because of failure to contain the infection following reactivation of the viruses and decreased cellular immunity against virally infected cells undergoing malignant transformation. The incidence of many of these tumors, especially Kaposi sarcoma, is decreasing as treatment has improved and patients have less immune compromise. Nevertheless, HIV-infected individuals remain more susceptible to tumors that occur in the general population, such as lung and skin cancers and certain forms of lymphoma.
Kaposi Sarcoma. Kaposi sarcoma (KS), a vascular tumor that is otherwise rare in the United States, is considered an AIDS-defining malignancy. The morphology of KS and its occurrence in patients not infected with HIV are discussed in Chapter 10. At the onset of the AIDS epidemic, up to 30% of infected homosexual or bisexual men had KS, but with use of HAART there has been a dramatic decline in its incidence in recent years. In contrast, in areas of sub-Saharan Africa where HIV infection is both frequent and largely untreated, Kaposi sarcoma is one of the most common tumors.
The lesions of KS are characterized by a proliferation of spindle-shaped cells that express markers of both endothelial cells (vascular or lymphatic) and smooth muscle cells.
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In addition, KS lesions contain chronic inflammatory cell infiltrates. Many of the features of KS suggest that it is not a malignant tumor (despite its ominous name).