by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer

September 15, 2020

Featured Literature:
Sereti I et al. Prospective International Study of Incidence and Predictors of Immune Reconstitution Inflammatory Syndrome and Death in People Living with HIV and Severe Lymphopenia. Clin Infect Dis August 1, 2020;71(3):652-60. DOI:10.1093/cid/ciz.877

Persons diagnosed with advanced HIV disease are at high risk for immune reconstitution inflammatory syndrome (IRIS) after initiation of ART. IRIS is generally described as an “inflammatory deterioration of clinical manifestations of infection (e.g. TB, MAC, CMV) or tumor” (KS) and is associated with significant morbidity and mortality. This study looked prospectively at the clinical impact of IRIS on 506 patients from the U.S., Kenya, and Thailand. The median age was 37 years and 40% were women. Their median baseline CD4 count was 29 cells/µL. Within six months of starting ART, 97 of the patients developed IRIS events and 31 ultimately died. Significant risks identified as being associated with IRIS were a low hemoglobin and lower CD4 count (< 30 cells/µL). Risk factors for death included being female, a low BMI, and an elevated D-dimer level. Additional analysis found having a high CRP level (>106 ug/mL) and very low BMI (<15.6 kg/m2) were also predictive of death. There was no association between IRIS and CD4 change at any time point including baseline. The authors believe these data may be helpful in predicting which patients are at risk for IRIS and to guide preventive interventions including antibiotics, antivirals, and corticosteroids in these patients concurrently with ART.

Author’s Commentary:

With routine HIV screening and earlier diagnoses, most patients these days have baseline CD4 counts > 200 with IRIS phenomena less commonly observed. However, the risk for IRIS remains for patients presenting late to care with advanced AIDS and concurrent but subclinical opportunistic infections. Treatment guidelines recommend early initiation of ART in patients with CD4 counts < 50 cells/µL except for individuals with cryptococcal meningitis or CNS-TB. For patients with low CD4 counts, obtaining a pre-treatment CRP and D-Dimer could help determine the need for oral prednisone or enhanced antimicrobial prophylaxis to help effectively mitigate IRIS events while patients are undergoing immune recovery with ART.

The author has no conflicts of interest to disclose.

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