Immunosuppressive Effects of Cancer Treatment Increase Mortality in People With HIV

By Will Boggs MD

December 11, 2019

NEW YORK (Reuters Health) - Adults with HIV whose cancers are treated with chemotherapy or radiotherapy experience significant reductions in CD4 count, which are linked to increased mortality, compared with those who have surgery or other treatment, according to findings from an observational study.

Some, but not all, studies have reported pronounced periods of immunosuppression in people with HIV after various chemotherapy and radiotherapy regimens. It also remains unclear whether such immunosuppression worsens outcomes among people with HIV.

Dr. Keri L. Calkins of Johns Hopkins Bloomberg School of Public Health, in Baltimore, Maryland, and colleagues compared longitudinal changes in CD4 count and HIV RNA level by cancer treatment type in 196 adults living with HIV. They also quantified the association between these biomarkers and all-cause mortality after cancer treatment.

Among the 60.2% of patients who received chemotherapy and/or radiotherapy, the median five-year mortality risk was significantly higher (37%) than that among the remaining patients who had surgery or other treatment (24%), the researchers report in JAMA Oncology.

Chemotherapy and/or radiotherapy was associated with a drop of 203 cells/uL in CD4 count relative to surgery or other treatment. But among patients with baseline CD4 counts of 350 cells/uL or fewer, this decline was only 45 cells/uL.

In contrast, for those who were virally suppressed, chemotherapy and/or radiotherapy did not change their HIV RNA level compared with surgery or other treatment. Patients who were unsuppressed at baseline, however, had greater-than-expected declines in HIV RNA level associated with receipt of chemotherapy and/or radiotherapy.

Each 100 cells/uL drop in CD4 count at any point during follow-up was associated with a significant 27% increased risk of mortality, whereas increases in HIV RNA level were not significantly associated with mortality.

"We believe the association between lower CD4 count after cancer treatment and higher mortality supports the hypothesis that immune status in persons with HIV can influence mortality after cancer diagnosis," the authors conclude.

"Further consideration of the immunosuppressive effects of cancer treatment in persons with HIV appears to be needed," they add. "For example, we think a comparison of these outcomes among persons with HIV with locoregional solid tumors undergoing surgery alone or surgery and adjuvant chemotherapy and/or radiotherapy would be a reasonable clinical scenario in which to further explore these results."

Dr. Thomas S. Uldrick of Fred Hutchinson Cancer Research Center and the University of Washington, in Seattle, who co-authored an invited commentary, told Reuters Health by email, "The immunosuppressive effects of many forms of chemotherapy and radiation therapy should be recognized for all patients. For patients with HIV, it is critical to untangle the effects of HIV versus that of therapy. This can be ascertained through evaluation of historic CD4 T-cell counts and as well as inquiring about a patient's history of opportunistic infections."

"This study does not alter the recommendation for standard-of-care therapy that includes concurrent antiretroviral therapy for most patients with HIV and cancer, but rather highlights the need to advance immunotherapeutic options in this patient population," he said.

"Don't assume low CD4-cell counts in a patient with HIV and cancer are due to underlying HIV," Dr. Uldrick said. "Appropriate interpretation of CD4-cell counts in this setting should inform cancer treatment and supportive care recommendations."

Dr. Keith Sigel of Icahn School of Medicine at Mount Sinai, in New York City, who has studied various aspects of cancer in persons with HIV (PWH), told Reuters Health by email, "It has been frequently reported in large cohort studies and population-based data analyses that persons with HIV often have worse cancer outcomes than similar uninfected persons. This study adds important and highly interesting information by showing that PWH with lowered CD4 after cancer treatment (independent of HIV viral control) had worse mortality. Therefore, this study suggests one potential mechanism driving worse outcomes in this group; however, there is no comparison to uninfected persons, so it is not possible to fully assess."

"The retrospective and nonexperimental nature of the study limits our ability to make management conclusions from this study," said Dr. Sigel, who was not involved in the research. "However, it does suggest that lower CD4 count after cancer treatment is a risk factor for mortality and, therefore, helps us to identify the highest risk groups. Antiretroviral adherence and adherence to appropriate antimicrobial prophylaxis should be emphasized in that group (those with large CD4 declines after cancer treatment)."

Dr. Calkins did not respond to a request for comments.

SOURCE: https://bit.ly/36mjxkY and https://bit.ly/2PudVhv JAMA Oncology, online December 5, 2019.

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