Our study, spanning a 10-year period since 1996, represents one of the largest to include HIV-infected and HIV-uninfected NHL cases identified from the same health system. We observed a 2-year mortality of 60% for HIV-infected NHL patients, a rate that is comparable to those seen in other observational studies (55%–78%) in the cART era [11
]. We found that overall, HIV-infected NHL patients continued to have a significantly elevated all-cause and lymphoma-specific mortality compared with NHL patients in the general population. However, HIV-infected patients with better controlled HIV disease, i.e., those whose NHL was the first AIDS-defining illness and was developed with a CD4 cell count level of 200/mm3
or greater did not have an increased risk for lymphoma-specific mortality compared to HIV-uninfected patients. This finding supports aggressive HIV disease management strategy for patients infected with HIV and potentially earlier start of cART [15
A previous study found similar survival for HIV-infected and HIV-uninfected NHL patients when response to chemotherapy was adjusted [17
]. The authors concluded that the lower complete remission rate achieved by the HIV-infected patients was the cause for the inferior survival for HIV-infected patients. It is possible that the low CD4 cell counts, which can be seen with advanced HIV disease, may be a predictor for undesirable treatment response or toxicity. However, studies evaluating the relationship of CD4 cell count and lymphoma treatment response were mixed [18
]. Future studies should further investigate the effect of HIV disease management on NHL treatment experience.
We found that non-DLBCL lymphoma histologic subtype, prior AIDS-defining illness, non-white race and CD4 cell count <200/mm3
were prognostic factors for all-cause mortality in HIV-infected patients. The prognostic role of lymphoma characteristics in HIV-infected NHL has been consistently reported in the cART era [18
]. However, contrary to the literature, more advanced stage disease was not a predictor for all-cause mortality among HIV-infected patients. The prognostic role of HIV disease factors (such as CD4 cell count, HIV RNA level, and cART use) in NHL has been less clear [18
]. Several population-based studies of HIV-related NHL, including the present one, reported low CD4 cell count and prior AIDS-defining illness to be important prognostic factors in the cART era [11
]. On the other hand, use of cART prior to NHL diagnosis was not predictive of overall survival in this study as well as others [12
There are several potential limitations in our study that should be considered when interpreting our results. Due to the observational study design, we did not have information on CD4 cell counts or HIV RNA levels at NHL diagnosis for many HIV-infected cases (), which could potentially have resulted in bias if survival was different for cases with and without such measurements. Another potential limitation came from the use of death certificate to determine lymphoma-specific death. As it was possible that some of the NHL-related deaths were vaguely coded with an underlying cause of HIV/AIDS, results for lymphoma-specific mortality should be interpreted with caution. Finally, generalizability of our results to persons without health insurance may be limited, or to other healthcare systems that do not have an integrated healthcare model.
In conclusion, our study showed a poor overall survival, approaching only 40% for HIV-infected patients after NHL diagnosis in the cART era, with no clear improvement over the 10-year study period. However, HIV-infected patients with higher CD4 cell counts and no prior AIDS-defining illness had a similar risk for lymphoma-specific death compared to NHL in the general population. These results emphasize the importance in preserving the immune function during the course of HIV disease management, and further evaluating optimal treatment options for HIV-infected NHL patients with severely suppressed immunity, which account for 50% of the HIV-related NHL in the cART era.