Immune Status and Associated Mortality After Cancer Treatment Among Individuals With HIV in the Antiretroviral Therapy Era
Authors: Keri L. Calkins, Geetanjali Chander, Corinne E. Joshu, Kala Visvanathan, Anthony T. Fojo, Catherine R. Lesko, Richard D. Moore, Bryan Lau
Journal: JAMA Oncology (2019)

<h3>Importance</h3> Immunologic decline associated with cancer treatment in people with HIV is not well characterized. Quantifying excess mortality associated with cancer treatment–related immunosuppression may help inform cancer treatment guidelines for persons with HIV. <h3>Objective</h3> To estimate the association between cancer treatment and CD4 count and HIV RNA level in persons with HIV and between posttreatment CD4 count and HIV RNA trajectories and all-cause mortality. <h3>Design, Setting, and Participants</h3> This observational cohort study included 196 adults with HIV who had an incident first cancer and available cancer treatment data while in the care of The Johns Hopkins HIV Clinic from January 1, 1997, through March 1, 2016. The study hypothesized that chemotherapy and/or radiotherapy in people with HIV would increase HIV RNA levels owing to treatment tolerability issues and would be associated with a larger initial decline in CD4 count and slower CD4 recovery compared with surgery or other treatment. An additional hypothesis was that these CD4 count declines would be associated with higher mortality independent of baseline CD4 count, antiretroviral therapy use, and risk due to the underlying cancer. Data were analyzed from December 1, 2017, through April 1, 2018. <h3>Exposures</h3> Initial cancer treatment category (chemotherapy and/or radiotherapy vs surgery or other treatment). <h3>Main Outcomes and Measures</h3> Post–cancer treatment longitudinal CD4 count, longitudinal HIV RNA level, and all-cause mortality. <h3>Results</h3> Among the 196 participants (135 [68.9%] male; median age, 50 [interquartile range, 43-55] years), chemotherapy and/or radiotherapy decreased initial CD4 count by 203 cells/μL (95% CI, 92-306 cells/μL) among those with a baseline CD4 count of greater than 500 cells/μL. The decline for those with a baseline CD4 count of no greater than 350 cells/μL was 45 cells/μL (interaction estimate, 158 cells/μL; 95% CI, 31-276 cells/μL). Chemotherapy and/or radiotherapy had no detrimental association with HIV RNA levels. After initial cancer treatment, every 100 cells/μL decrease in CD4 count resulted in a 27% increase in mortality (hazard ratio, 1.27; 95% CI, 1.08-1.53), adjusting for HIV RNA level. No significant increase in mortality was associated with a unit increase in log<sub>10</sub>HIV RNA after adjusting for CD4 count (hazard ratio, 1.24; 95% CI, 0.94-1.65). <h3>Conclusions and Relevance</h3> In this study, chemotherapy and/or radiotherapy was associated with significantly reduced initial CD4 count in adults with HIV compared with surgery or other treatment. Lower CD4 count after cancer treatment was associated with an increased hazard of mortality. Further research is necessary on the immunosuppressive effects of cancer treatment in adults with HIV and whether health care professionals must consider the balance of cancer treatment efficacy against the potential cost of further immunosuppression. Monitoring of immune status may also be helpful given the decrease in CD4 count after treatment and the already immunocompromised state of patients with HIV.