Prospective international study of incidence and predictors of immune reconstitution inflammatory syndrome and death in people with HIV and severe lymphopenia

Patients with HIV and low CD4 counts starting antiretroviral therapy (ART) are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death. To investigate the clinical impact of IRIS in adults with HIV and CD4 counts below 100 cells/µL starting ART, we designed an international, prospective, observational study in United States, Thailand, and Kenya. An independent review committee adjudicated IRIS events. We used Cox models to investigate associations between baseline biomarkers, IRIS, immune recovery at week 48, and death by week 48. We enrolled 506 participants, 39.3% of whom were women. Median age was 37 years (IQR 31-45) and CD4 T cell count was 29 cells/µL (IQR 11-56). Within 6 months of ART initiation, 97 (19.2%) participants developed IRIS and 31 (6.5%) died. Participants with lower hemoglobin at study start were at higher risk of IRIS (HR 1.2, p=0.004). IRIS was independently associated with increased risk of death even after adjustment for known risk factors (HR 3.2, P=0.031). In addition, being female (P=0.004), having lower BMI (P=0.003), higher WBC (P=0.005) and higher D-dimer levels (P=0.044) were also significantly associated with increased risk of death. Decision tree analysis identified hemoglobin less than 8.5 g/dL as highly predictive of IRIS and CRP>106 µg/ml and BMI < 15.6 kg/m2 as predictive of death . For patients with HIV and severe immunosuppression who are initiating ART, baseline low BMI and hemoglobin, and high CRP and D-dimer may be clinically useful predictors of IRIS and death risk. Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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