Lymphoma mortality rates remain elevated among HIV-positive people in the United States

HIV-positive people in the United States diagnosed with certain types of lymphoma continue to have poorer outcomes compared to HIV-negative lymphoma patients, according to research published in the Journal of the National Cancer Institute.

The study involved 23,000 people who received HIV care in the antiretroviral therapy era – 1996 to 2010. Overall, the age at which individuals were diagnosed with lymphoma increased, reflecting the general ageing of the HIV-infected population. There were also shifts in the type of lymphoma diagnosed, with an increasing proportion of non-Hodgkin lymphoma involving a diagnosis of Burkitt lymphoma. Despite improvements in HIV treatment and care, a low CD4 cell count continued to be a characteristic of people diagnosed with lymphoma.

“Patients continue to have severe antecedent immune suppression evidenced by static nadir CD4 counts over time,” the authors comment.

Between a quarter and a third of all deaths in HIV-positive individuals are due to cancer, with many of these deaths due to lymphomas.

Thanks to antiretroviral therapy, the prognosis of most people with HIV is now excellent. European research has shown that HIV-positive people diagnosed with Hodgkin and non-Hodgkin lymphoma now have survival rates similar to those observed in HIV-negative individuals. In contrast, research from the United States suggests that outcomes continue to be poorer for HIV-positive people with non-Hodgkin lymphoma.

Given this discrepancy, a team of investigators looked at lymphoma diagnosis trends among 23,000 people who received HIV care in the United States between 1996 and 2010. Mortality rates and predictors of outcome were also examined.

A total of 476 participants (2%) were diagnosed with a lymphoma, with 79 cases (17%) involving a diagnosis of Hodgkin lymphoma (HL). There were 201 cases (42%) of diffuse large B-cell lymphoma (DLBCL); 56 cases (12%) of Burkitt lymphoma (BL); 54 (11%) lymphomas of the central nervous system and 86 (18%) diagnoses involving another form of non-Hodgkin lymphoma.

A total of 223 (47%) of lymphomas involved people who were already taking antiretroviral therapy. The overall median CD4 cell count at the time of lymphoma diagnosis was 119 cells/mm³ and the participants had a median nadir CD4 cell count of just 52 cells/mm³.

Individuals diagnosed with Hodgkin lymphoma were more likely than individuals with non-Hodgkin lymphoma to be black (p = 0.01), to be taking antiretroviral therapy (p < 0.001), to have a higher CD4 cell count (p = 0.01) and to have an undetectable viral load (p < 0.001).

There were also differences in the characteristics of people diagnosed with the different forms of non-Hodgkin lymphoma.

Individuals with lymphoma of the central nervous system were more likely to be male (p < 0.001), black (p = 0.003), and have a lower nadir CD4 cell count (p < 0.001) and a lower CD4 cell count at the time of cancer diagnosis (p = 0.006) than other non-Hodgkin lymphoma patients. In addition, people with Burkitt lymphoma had higher nadir CD4 cell counts (p = 0.006) and stronger immune systems at the time of lymphoma diagnosis (p < 0.001) compared to individuals without this cancer.

The proportion of non-Hodgkin lymphoma involving a diagnosis of Burkitt lymphoma increased steadily and significantly over the period of the study (p = 0.02). The proportion of lymphoma diagnoses involving a diagnosis of Hodgkin lymphoma fell from 44% between 1996 and 2002 to 36% between 2006 and 2010.

Age at the time of cancer diagnosis increased from a mean of 40 years in the period before 2000 to a mean of 45 years in the period 2006 to 2010 (p < 0.001). There was also a significant increase in the proportion of diagnoses involving gay men (40 to 53%, p = 0.03).

Median CD4 cell count at the time of lymphoma diagnosis increased from 85 cells/mm³ at the start of the study period to 166 cells/mm³ in the period 1996 to 2010 (p = 0.004). The proportion of participants with an undetectable viral load also increased (p = 0.006). However, nadir CD4 cell count remained stubbornly unchanged throughout the 14 years of analysis.

There were 225 deaths during 1525 years of follow-up, providing an overall mortality rate of 15 deaths per 100 person-years.

There was a 62% five-year survival rate for people with Hodgkin lymphoma. Half the participants with Burkitt lymphoma were alive five years after diagnosis as were 44% of those with diffuse large B-cell lymphoma, 43% of people with other forms of non-Hodgkin lymphoma and 22% of individuals diagnosed with primary lymphoma of the central nervous system.

“By comparison,” write the investigators, “5-year survival rates for all United States adults aged less than 65 with HL, BL, DLBCL diagnosed between 2001 and 2007 were 88.4%, 50.5% and 68.7%. Our data therefore suggest that [HIV] patients…with HL and DLBCL fare worse than HIV-uninfected patients.”

There were significant improvements in HIV therapy over the course of the study. However, these were not reflected in mortality trends, which remained largely unchanged.

Independent risk factors for mortality included older age (AHR per additional decade = 1.28; 95% CI, 1.06-1.54); diagnosis of lymphoma while taking HIV therapy (AHR = 2.21; 95% CI, 1.53-3.20), lower CD4 cell count (AHR = 0.81 per 100 cell/mm³ increase; 95% CI, 0.72-0.90) and higher viral load (AHR = 1.13 per log₁₀ copies/ml; 95% CI, 1.00-1.27).

“HIV-associated lymphoma is highly heterogeneous in the current era, and important demographic, immunologic, virologic, and histologic shifts are occurring,” conclude the investigators. “Outcomes remain inferior to registry data for the general population. These results highlight an ongoing need to elucidate lymphoma biology and optimize treatment for this challenging population to reduce deaths from one of the leading causes of mortality in the modern ART era.”