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      Immune Status and Associated Mortality After Cancer Treatment Among Individuals With HIV in the Antiretroviral Therapy Era

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          Abstract

          <p class="first" id="d361177e351">This cohort study assesses the association between cancer treatment and CD4 count and RNA levels in adults with human immunodeficiency virus. </p><div class="section"> <a class="named-anchor" id="ab-coi190090-1"> <!-- named anchor --> </a> <h5 class="title" id="d361177e357">Question</h5> <p id="d361177e359">What is the association between cancer treatment and CD4 count and HIV RNA level, and how are these markers associated with all-cause mortality among people with HIV? </p> </div><div class="section"> <a class="named-anchor" id="ab-coi190090-2"> <!-- named anchor --> </a> <h5 class="title" id="d361177e362">Findings</h5> <p id="d361177e364">In a clinical cohort study of 196 adults with HIV and cancer, chemotherapy and/or radiotherapy resulted in a decline in CD4 count of 203 cells/μL shortly after treatment compared with other cancer treatments but did not increase HIV RNA level. Every decline in CD4 count of 100 cells/μL was associated with a 27% increase in mortality. </p> </div><div class="section"> <a class="named-anchor" id="ab-coi190090-3"> <!-- named anchor --> </a> <h5 class="title" id="d361177e367">Meaning</h5> <p id="d361177e369">These results suggest that the immunosuppressive effects of cancer treatments should be considered in the development of cancer treatment recommendations specific to people with HIV. </p> </div><div class="section"> <a class="named-anchor" id="ab-coi190090-4"> <!-- named anchor --> </a> <h5 class="title" id="d361177e373">Importance</h5> <p id="d361177e375">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. </p> </div><div class="section"> <a class="named-anchor" id="ab-coi190090-5"> <!-- named anchor --> </a> <h5 class="title" id="d361177e378">Objective</h5> <p id="d361177e380">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. </p> </div><div class="section"> <a class="named-anchor" id="ab-coi190090-6"> <!-- named anchor --> </a> <h5 class="title" id="d361177e383">Design, Setting, and Participants</h5> <p id="d361177e385">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. </p> </div><div class="section"> <a class="named-anchor" id="ab-coi190090-7"> <!-- named anchor --> </a> <h5 class="title" id="d361177e388">Exposures</h5> <p id="d361177e390">Initial cancer treatment category (chemotherapy and/or radiotherapy vs surgery or other treatment). </p> </div><div class="section"> <a class="named-anchor" id="ab-coi190090-8"> <!-- named anchor --> </a> <h5 class="title" id="d361177e393">Main Outcomes and Measures</h5> <p id="d361177e395">Post–cancer treatment longitudinal CD4 count, longitudinal HIV RNA level, and all-cause mortality. </p> </div><div class="section"> <a class="named-anchor" id="ab-coi190090-9"> <!-- named anchor --> </a> <h5 class="title" id="d361177e398">Results</h5> <p id="d361177e400">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). </p> </div><div class="section"> <a class="named-anchor" id="ab-coi190090-10"> <!-- named anchor --> </a> <h5 class="title" id="d361177e406">Conclusions and Relevance</h5> <p id="d361177e408">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. </p> </div>

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          Most cited references39

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          Elevated Cancer-Specific Mortality Among HIV-Infected Patients in the United States.

          Despite advances in the treatment of HIV, HIV-infected people remain at increased risk for many cancers, and the number of non-AIDS-defining cancers is increasing with the aging of the HIV-infected population. No prior study has comprehensively evaluated the effect of HIV on cancer-specific mortality.
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            Joint Models for Longitudinal and Time-to-Event Data

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              Cancer treatment disparities in HIV-infected individuals in the United States.

              HIV-infected individuals with cancer have worse survival rates compared with their HIV-uninfected counterparts. One explanation may be differing cancer treatment; however, few studies have examined this.
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                Author and article information

                Journal
                JAMA Oncology
                JAMA Oncol
                American Medical Association (AMA)
                2374-2437
                December 05 2019
                Affiliations
                [1 ]Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
                [2 ]School of Medicine, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland
                [3 ]School of Medicine, Department of Medical Oncology, The Johns Hopkins University, Baltimore, Maryland
                Article
                10.1001/jamaoncol.2019.4648
                6902188
                31804663
                b3d960d1-3394-4ac8-9648-d8738f9121fc
                © 2019
                History

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