Prospective International Study of Incidence and Predictors of Immune Reconstitution Inflammatory Syndrome and Death in People Living With Human Immunodeficiency Virus and Severe Lymphopenia

Abstract

Background Patients with HIV and low CD4 counts starting antiretroviral therapy (ART) are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death. Methods 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. Results 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 . Conclusions 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.

HIV Populations Shift After Tuberculosis Associated Immune Reconstitution Inflammatory Syndrome: Implications For HIV Remission

“…No signi cant elevations were detected in pre-cART levels of CRP, IL-2, IL-10, IL-8, soluble CD163 or hepcidin (Table S2). These data demonstrate that individuals with TB-IRIS had substantial systemic in ammation, as previously reported (26).…”

Impact of Persistent Anemia on Systemic Inflammation and Tuberculosis Outcomes in Persons Living With HIV

“…Whether anemia sets the stage for persistent inflammation or is just a hallmark of chronic, unfettered, dysregulation of inflammatory responses warrants further investigation. This association between low Hb levels and risk of inflammatory disturbance has been described in PLHW who experience IRIS (33,34) and also in patients with HIV/TB coinfection (35).…”

The triggering of post-COVID-19 autoimmunity phenomena could be associated with both transient immunosuppression and an inappropriate form of immune reconstitution in susceptible individuals

“…Similar phenomena are observed in clinical practice, where a form of transient immunosuppression or immunodeficiency occurs before a sudden reactivation of the immune components, which is associated with the triggering of autoimmunity or autoinflammation phenomena. This is the case with postpartum [46] , withdrawal of chemotherapy for cancer [47] , withdrawal of glucocorticoids [48] , withdrawal of anti-TNF medication in patients with tuberculosis [49] , or initiation of treatment for HIV infection [50] , among others.…”