Search

Older individuals (>50 years of age) now comprise over 11% of patients with AIDS in the United States. This percentage is expected to continue to grow, due both to the improved longevity of patients prescribed highly active antiretroviral therapy (HAART) and to new infections among older individuals. This review focuses on the neuropsychiatric and neurological conditions that are most likely to be affected by advancing age-HIV-1-associated cognitive-motor disorder, peripheral neuropathy, progressive multifocal leukoencephalopathy, primary CNS lymphoma, and risk for cerebrovascular accident. Age associations with incidence of these disorders and with treatment foci are specified. Implications for future changes in management are discussed.

We describe the anatomic and histologic presentation and prognosis of non-Hodgkin's lymphoma (NHL) among people with AIDS (PWA) and determine their contribution to the NHL burden. We linked AIDS and cancer registries in selected areas of the United States and compared NHL sites and histologies in PWA and non-PWA, after adjusting for age, sex and ethnicity. Among 51,033 PWA, we found 2,156 cases of NHL (4.3%). Half of NHL cases occurring post-AIDS were not reported to AIDS registries. NHL was part of an AIDS-defining condition for 3.2% of all PWA; the relative risk of NHL with 3.5 years of another AIDS diagnosis was 165-fold compared to non-PWA within the cancer surveillance system. Of NHLs, 39% were high grade (vs. 12% among non-PWA), 60% were nodal (vs. 74% among non-PWA) and 15% had brain primaries (vs. 1% among non-PWA). Excluding brain sites, extranodal sites were still 20% more common than expected. Relative risk was elevated for all histologic types, with the risk ranging from 652-fold for high-grade diffuse immunoblastic tumors and 261-fold for Burkitt's lymphomas to 113 for intermediate-grade lymphoma to 14-fold for low-grade lymphoma. Survival among PWA with NHL was poor, and tumor grade had little impact. In high-risk AIDS areas, AIDS-related NHLs constitute a major share of the NHL burden. We conclude that NHL risk is considerably under-estimated in AIDS registry data. The major differences between PWA and non-PWA were the high frequency of brain lymphoma and the increase in high-grade lymphomas in PWA. However, the grade of NHL did not influence the prognosis among PWA with lymphoma. The increasing risk of NHL in PWA has contributed substantially to the general increase in NHL rates in the United States since 1981.

The incidence of NHL is greatly increased in HIV-infected individuals. The vast majority are clinically aggressive B cell-derived neoplasms exhibiting BL, IBL, or LCL histology. Approximately 80% arise systemically (nodal and/or extranodal), and the remaining 20% arise as primary CNS lymphomas. A small proportion are body cavity-based lymphomas associated with KSHV infection. Possible factors contributing to lymphoma development include HIV-induced immunosuppression, chronic antigenic stimulation, and cytokine overproduction. These alterations are associated with the development of oligoclonal B-cell expansions. The appearance of NHL is characterized by the presence of a monoclonal B-cell population displaying a variety of genetic lesions, including EBV infection, c-myc gene rearrangement, bcl-6 gene rearrangement, ras gene mutations, and p53 mutations/deletions. The number and type of genetic lesions varies according to the anatomic site and histopathology. In the case of BL, virtually 100% exhibit c-myc gene rearrangements, two thirds display p53 gene mutations, one third contain EBV, and none exhibit bcl-6 gene rearrangements. In contrast, in the case of IBL, virtually 100% contain EBV, 25% display c-myc gene rearrangements, 20% display bcl-6 gene rearrangements, and very few exhibit p53 gene mutations. These findings suggest that more than one pathogenetic mechanism is operational in the development and progression of AIDS-related NHLs. Further work will be necessary to develop a complete understanding of the etiology and pathogenesis of NHL in the setting of HIV infection. AIDS-related NHL remains an important biologic model for investigating the development and progression of high-grade NHLs as well as NHLs that develop in immune-deficient hosts.

The magnitude for and risk factors of the two most important AIDS neoplasm, Kaposi's sarcoma and non-Hodgkin's lymphoma, are reviewed in detail. The association between AIDS and other cancers is mostly speculative because surveillance biases tend to favor detecting associations that may be spurious. The overall relative risk of other cancers appears, however, to be only twofold above that in the general population, with associations being most convincing for anal (but not cervical) cancer and leiomyosarcoma and possible also for Hodgkin's disease, testicular cancer, and conjunctival cancers.

The possibility that an agent in addition to the human immunodeficiency virus (HIV) may contribute to the etiology of non-Hodgkin's lymphoma in persons with acquired immunodeficiency syndrome (AIDS) was studied using participants from the Multicenter AIDS Cohort Study (MACS) of homosexual and bisexual men enrolled in 1984-1985 and also in 1987-1991. A nested case-control analysis was conducted. The primary source of information on potential exposures and characteristics of the participants was the baseline study entry interview that was conducted prior to the development of AIDS. A total of 84 cases of non-Hodgkin's lymphoma were identified and compared with 527 participants who developed AIDS but had no evidence of cancer. The groups were similar for most sociodemographic characteristics as well as sexual activity and past history of antecedent illnesses. Although the non-Hodgkin's lymphoma cases reported less frequent use of recreational drugs and cigarettes compared with other persons with AIDS, these differences were not significant. Non-Hodgkin's lymphoma cases reported more frequent intake of aspirin during the week before the interview. However, there were no differences between the comparison groups for long-term aspirin intake or intake of other analgesics. The absence of any specific and strong association between non-Hodgkin's lymphoma and the various behavior-related activities and exposures considered in this analysis suggests that these factors are not related to a second agent in the etiology of HIV-induced non-Hodgkin's lymphoma. The possibility that a very common agent in this study population or that differences in the nature of the immune dysfunction resulting from HIV infection could act as a cofactor for HIV-induced non-Hodgkin's lymphoma cannot be excluded.

The excess of NHL associated with HIV infection is well established. Clinically, HIV associated NHL is characterized by histological evidence of a high grade of malignancy, B cell origin, extensive extranodal involvement (most notably of the CNS) and poor prognosis. High grade B cell lymphoma or primary brain lymphoma in HIV infected individuals is considered diagnostic of AIDS by the Centers for Disease Control. The incidence of NHL among individuals with AIDS varies by subtype of lymphoma, age, sex, race and risk group. Younger individuals, males, whites and haemophiliacs are at higher risk than other groups. The incidence of HIV associated NHL is increasing. Because of the paucity of data on risk factors for this malignancy, the current possibilities for risk modification are limited to the prevention of HIV infection.