ABSTRACT
Introduction 1421 Epidemiology 1421 Etiology and pathogenesis 1422 Pathology 1425 Category I lymphomas 1425 Category II lymphomas 1426 Category III lymphomas 1426 Clinical presentation 1426 Diagnostic evaluation 1427 Clinical and molecular prognostic factors 1427 Treatment 1428 The pre-HAART era 1428 The HAART era 1428
HAART suspension during chemotherapy 1430 The role of rituximab in AIDS-related lymphoma 1431 Burkitt lymphoma in the HAART era 1432 Treatment at recurrence 1432 Other HIV-associated lymphoproliferative diseases 1433 Hodgkin lymphoma 1433 Primary central nervous system lymphoma 1433 Primary effusion and plasmablastic lymphoma 1433 Castleman disease 1434 Conclusions 1434 Key points 1434 References 1434
Human immunodeficiency virus (HIV) infection continues to be a pandemic of unrelenting and unprecedented pervasiveness. Lymphoid neoplasms are an important complication of HIV infection where they occur with increased frequency and are a significant cause of morbidity and mortality. While most lymphoma subtypes principally occur in immunocompetent patients, for example, diffuse large B cell lymphoma (DLBCL), others are primarily associated with HIV infection, such as primary effusion lymphoma (PEL) and plasmablastic lymphoma (PBL) of the oral cavity. Overall, HIV-associated lymphoid neoplasms are both histologically and clinically aggressive. With the everincreasing prevalence of HIV infection, these disorders are becoming more widely diagnosed. It is fortunate that HAART (highly active antiretroviral therapy) has reduced the incidence and improved the outcome of acquired immune deficiency syndrome (AIDS)-related lymphomas (ARL), in large measure due to better control of HIV replication and enhanced immune function. Sadly though, affected populations in continents with the highest prevalence of HIV, such as sub-Saharan Africa, have little access to HAART and this should be kept in mind when considering
In the setting of HIV infection, several distinct subtypes of non-Hodgkin lymphoma (NHL) are encountered with varying frequencies. While the overall increased risk of NHL is greater than 100-fold, the incidence of primary central nervous system lymphoma (PCNSL) is increased 3600-fold and Burkitt lymphoma 1000-fold when compared to HIV-negative populations.1-4 Though not AIDSdefining illnesses, the relative risk of other lymphoid neoplasms such as Hodgkin lymphoma (HL), extranodal marginal zone lymphoma, and certain T cell lymphomas also appears increased in the setting of HIV infection.5-8
Several studies have investigated the impact of HAART on the incidence of ARL. The results of these studies have been somewhat confusing. A few studies found no change in the incidence of ARL in the post-HAART era but it is likely that these studies suffered from inadequate design.9,10
They compared the incidence of ARL in different time periods but did not examine or compare factors such as population demographics, CD4 cell number, access to and compliance with HAART therapy, or patterns of HIV-drug resistance within populations; factors that potentially impact the incidence of ARL. Other studies, however, have
international study of 47 936 HIV-positive patients from 23 prospective studies.11 When all data were combined, the adjusted incidence rate per 1000 person-years of NHL declined from 6.2 to 3.6 over the periods of 1992-1996 and 1997-1999, respectively. Other studies have also confirmed this decline.13-15 Interestingly, when analyzed by lymphoma subtype, a decline was observed in PCNSL and immunoblastic DLBCL, which are more common in patients with low CD4 cell counts. No decline was observed in Burkitt lymphoma, which is more common in patients with higher CD4 cell counts (Fig. 81.1A). This observation is not inconsistent with results from a large European study. In this study, the overall incidence of ARL dropped from 86 to 42.9 between the pre-and post-HAART eras, while PCNSL incidence fell from 27.8 to 9.7 per 10 000 person-years (Fig. 81.1B).12 However, when the authors compared the incidence of ARL and PCNSL within CD4 cell count strata, they found no differences. This suggests that the decline is due to a reduced proportion of patients with lower CD4 counts in whom the incidence of lymphoma is highest (Fig. 81.1B). The incidence of Hodgkin lymphoma does not appear to have changed since the use of HAART.11,13 It is important to recognize, however, that the overall beneficial effects of HAART on immune function seen over the past several years may decline as HIV resistance emerges, resulting in a rise in the overall incidence of HIV-associated lymphomas.
