Preprint
Clinical and immunologic predictors of Mycobacterium avium complex immune reconstitution inflammatory syndrome in a contemporary cohort of patients with HIV
Registro en:
BREGLIO, Kimberly F. et al. Clinical and immunologic predictors of Mycobacterium avium complex immune reconstitution inflammatory syndrome in a contemporary cohort of patients with HIV. Journal of Infectious Diseases, p. 1-26, 2020.
0022-1899
10.1093/infdis/jiaa669
Autor
Breglio, Kimberly F.
Vinhaes, Caian L.
Arriaga Gutiérrez, María Belen
Nason, Martha
Roby, Gregg
Adelsberger, Joseph
Andrade, Bruno de Bezerril
Sheikh, Virginia
Sereti, Irini
Resumen
Intramural Research program of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH). This research was also made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc, The Doris Duke Charitable Foundation, The Alexandria Real Estate Equities, Inc. and Mr. and Mrs. Joel S. Marcus, and the Howard Hughes Medical Institute, as well as other private donors. The work of BBA is supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; senior fellow) and by the Intramural Research Program of the Fundação Oswaldo Cruz, Brazil. CLV received a research fellowship from CNPq. MBA received a research fellowship from the Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). Background: Patients with HIV (PWH) can present with new or worsening symptoms associated with Mycobacterium avium complex (MAC) infection shortly after antiretroviral therapy (ART) initiation as MAC immune reconstitution inflammatory syndrome (MAC-IRIS). In this study, we assessed the utility of several laboratory tests as predictors of MAC-IRIS.
Methods: PWH with clinical and histologic and/or microbiologic evidence of MAC-IRIS were identified and followed up to 96 weeks post-ART initiation within a prospective study of 206 ART-naïve patients with CD4 <100 cells/μL.
Results: Fifteen (7.3%) patients presented with MAC-IRIS within a median interval of 26 days after ART initiation. Patients who developed MAC-IRIS had lower BMI, lower hemoglobin levels, a higher alkaline phosphatase and increased CD38 frequency and MFI on CD8+ T-cells, at the time of ART initiation compared to non-MAC IRIS patients. A decision tree inference model revealed that stratifying patients based on levels of alkaline phosphatase and D-dimer could predict the likelihood of MAC-IRIS. A binary logistic regression demonstrated that higher levels of alkaline phosphatase at baseline were associated with increased risk of MAC-IRIS development.
Conclusions: High alkaline phosphatase levels and increased CD8+ T-cell activation with low CD4 counts at ART initiation should warrant suspicion for subsequent development of MAC-IRIS.