We recently read with interest Kirk et al's paper “Non-Hodgkin lymphoma in HIV-infected patients in the era of highly active antiretroviral therapy.” 1 The authors analyzed the incidence and clinical characteristics of HIV-infected patients with primary central nervous system non-Hodgkin lymphoma (PCNS-NHL) and 3 categories of systemic non-Hodgkin lymphoma (S-NHL) according to their history of highly active antiretroviral therapy (HAART). The authors concluded that there was a significant decline in the incidence of PCNS-NHL and all 3 subtypes of S-NHL. Two issues could be raised about the data upon which this conclusion is based. First, it is important to point out that 47% (46 of 97) of the S-NHL cases in HIV-infected patients receiving HAART were categorized as “other/unknown.” This makes it difficult to determine the incidence of the different histologic types of S-NHL in this group of patients. Second, the median CD4 count and plasma HIV RNA viral load in patients with S-NHL receiving HAART were 108 cells/μL (range, 33 cells/μL to 223 cells/μL) and 4.0 log10 copies/mL, respectively. These data lead to the suggestion that S-NHL may be the result of stimulation and proliferation of B lymphocytes due to sustained HIV replication in these patients.
In contrast, a recent study of S-NHL among HIV-infected patients receiving HAART during the period of 1996-2000 at our community program located in Houston, Texas indicated that S-NHL is associated with higher CD4 cell counts.2 But no significant difference in the histologic types of this malignancy was observed among patients naive to antiretroviral drugs, as compared with those receiving HAART. More importantly, the analysis of HIV-infected patients with S-NHL who were receiving HAART indicated that 35% (12 of 34) had both HIV RNA viral load below the level of detection (< 400 copies/mL) and higher CD4 cell counts (median, 301 cells/μL; range, 46 cells/μL to 667 cells/μL). Such findings support the hypothesis that factors promoting the development of lymphoma may not be related to immunodysfunction or may be associated with processes not affected by HAART. Further studies are required to clarify the incidence and the pathogenesis of S-NHL in HIV-infected patients receiving HAART. Although the goal of antiretroviral therapy is the complete suppression of HIV replication,3,4 failure to achieve this goal is common in clinical practice, occurring at a rate of 40% to 70%.5-7 Furthermore, it is believed that the efficacy of present antiretroviral therapy may allow more persons with HIV infection to survive with long-term mild-to-moderate immunosuppression and some degree of continuing B-cell stimulation, thereby placing such patients at risk for the development of S-NHL.
