Irini Sereti1, Virginia Sheikh1, Douglas Shaffer2,3, Nittaya Phanuphak4, Erin Gabriel5, Jing Wang6, Martha C Nason7, Gregg Roby1, Hellen Ngeno2, Fredrick Kirui8, Alice Pau1, Joann M Mican1, Adam Rupert9, Rachel Bishop10, Brian Agan11,12, Nitiya Chomchey4, Nipat Teeratakulpisarn4, Somsit Tansuphaswadikul13, Deborah Langat8,12, Josphat Kosgei8,12, Martyn French14, Jintanat Ananworanich4,12,15,16, Fredrick Sawe8,12. 1. Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. 2. Walter Reed Army Institute of Research/US Army Medical Research Directorate-Africa, Nairobi, Kenya. 3. Walter Reed Army Institute of Research, US Military Human Immunodeficiency Virus Research Program, Silver Spring, Maryland, USA. 4. South East Asia Research Collaboration with Hawaii, Thai Red Cross AIDS Research Centre, Bangkok, Thailand. 5. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. 6. Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc, National Cancer Institute Campus at Frederick, Maryland, USA. 7. Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. 8. Kenya Medical Research Institute/US Army Medical Research Directorate-Africa-Kenya/ Henry Jackson Foundation Medical Research International, Kericho Clinical Research Center, Kenya. 9. Applied and Developmental Research Directorate, AIDS Monitoring Laboratory, Leidos Biomedical Research, Inc, Frederick, Maryland, USA. 10. National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. 11. Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. 12. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA. 13. Bamrasnaradura Infectious Diseases Institute, Department of Medicine, Nonthaburi, Thailand. 14. University of Western Australia, Medical School and School of Biomedical Sciences, Nedlands, Australia. 15. US Military Human Immunodeficiency Virus Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA. 16. Department of Global Health, Amsterdam Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Abstract
BACKGROUND: Patients living with human immunodeficiency virus (PLWH) with low CD4 counts are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death at antiretroviral therapy (ART) initiation. METHODS: We investigated the clinical impact of IRIS in PLWH and CD4 counts <100 cells/μL starting ART in an international, prospective study in the United States, Thailand, and Kenya. An independent review committee adjudicated IRIS events. We assessed associations between baseline biomarkers, IRIS, immune recovery at week 48, and death by week 48 with Cox models. RESULTS: We enrolled 506 participants (39.3% were women). Median age was 37 years, and CD4 count was 29 cells/μL. Within 6 months of ART, 97 (19.2%) participants developed IRIS and 31 (6.5%) died. Participants with lower hemoglobin at baseline were at higher IRIS risk (hazard ratio [HR], 1.2; P = .004). IRIS was independently associated with increased risk of death after adjustment for known risk factors (HR, 3.2; P = .031). Being female (P = .004) and having a lower body mass index (BMI; P = .003), higher white blood cell count (P = .005), and higher D-dimer levels (P = .044) were also significantly associated with increased risk of death. Decision-tree analysis identified hemoglobin <8.5 g/dL as predictive of IRIS and C-reactive protein (CRP) >106 μg/mL and BMI <15.6 kg/m2 as predictive of death. CONCLUSIONS: For PLWH with severe immunosuppression initiating ART, baseline low BMI and hemoglobin and high CRP and D-dimer levels may be clinically useful predictors of IRIS and death risk. Published by Oxford University Press for the Infectious Diseases Society of America 2019.
BACKGROUND:Patients living with human immunodeficiency virus (PLWH) with low CD4 counts are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death at antiretroviral therapy (ART) initiation. METHODS: We investigated the clinical impact of IRIS in PLWH and CD4 counts <100 cells/μL starting ART in an international, prospective study in the United States, Thailand, and Kenya. An independent review committee adjudicated IRIS events. We assessed associations between baseline biomarkers, IRIS, immune recovery at week 48, and death by week 48 with Cox models. RESULTS: We enrolled 506 participants (39.3% were women). Median age was 37 years, and CD4 count was 29 cells/μL. Within 6 months of ART, 97 (19.2%) participants developed IRIS and 31 (6.5%) died. Participants with lower hemoglobin at baseline were at higher IRIS risk (hazard ratio [HR], 1.2; P = .004). IRIS was independently associated with increased risk of death after adjustment for known risk factors (HR, 3.2; P = .031). Being female (P = .004) and having a lower body mass index (BMI; P = .003), higher white blood cell count (P = .005), and higher D-dimer levels (P = .044) were also significantly associated with increased risk of death. Decision-tree analysis identified hemoglobin <8.5 g/dL as predictive of IRIS and C-reactive protein (CRP) >106 μg/mL and BMI <15.6 kg/m2 as predictive of death. CONCLUSIONS: For PLWH with severe immunosuppression initiating ART, baseline low BMI and hemoglobin and high CRP and D-dimer levels may be clinically useful predictors of IRIS and death risk. Published by Oxford University Press for the Infectious Diseases Society of America 2019.
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