Open forum infectious diseases · 2025
Monocyte Activation in People With HIV and Tuberculosis Coinfection and Effect of Tuberculosis Preventive Therapy: An Analysis of the ACTG A5279/BRIEF TB Trial.
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Huaman Moises A, Feria Manuel G, Kendall Michelle A, McKhann Ashley, Supparatpinyo Khuanchai, Chougnet Claire A, Du Xinyu, Sawe Frederick K, Erlandson Kristine M, Utay Netanya S, Lederman Michael M, Swindells Susan, Gupta Amita, Chaisson Richard E, Fichtenbaum Carl J
Аннотация
BACKGROUND: Monocyte activation contributes to the pathogenesis of inflammation-driven comorbidities in people with HIV (PWH). We investigated the impact of tuberculin skin test (TST)/interferon-γ release assay (IGRA) status and tuberculosis preventive therapy (TPT) on monocyte activation in PWH.
METHODS: We analyzed peripheral blood mononuclear cells from participants from the A5279/BRIEF-TB trial, which compared 1 month of rifapentine/isoniazid (1HP) versus 9 months of isoniazid (9H) as TPT in PWH. All included participants were on suppressive antiretroviral therapy and had available TST or IGRA results at study entry. Samples collected at week 0 (pre-TPT) and week 48 (post-TPT) were analyzed. Monocyte subset and activation markers were measured using multiparameter flow cytometry. Proinflammatory cytokines (IL-6 and TNF-α) were assessed after 6-hour lipopolysaccharide (LPS) stimulation. Linear regression models were used for primary comparisons of monocyte markers by TST/IGRA status, adjusted for age, sex, country, and CD4 count.
RESULTS: In adjusted models, compared with TST/IGRA-negative participants (n = 27), TST/IGRA-positive participants (n = 30) had ∼2-fold relative increases in the median fluorescence intensity of CD64 (unstimulated) and CCR2 (post-LPS) on total monocytes and across monocyte subsets, pre- and post-TPT. Among TST/IGRA-positive participants, 1HP was associated with decreased fold changes over time for the percentage of CCR2+ monocytes and blunted IL-6/TNF-α responses compared with 9H.
CONCLUSIONS: PWH with a positive TST or IGRA exhibited signals of monocyte activation pre- and post-TPT. TPT with 1HP led to blunted proinflammatory monocyte changes compared with 9H.
METHODS: We analyzed peripheral blood mononuclear cells from participants from the A5279/BRIEF-TB trial, which compared 1 month of rifapentine/isoniazid (1HP) versus 9 months of isoniazid (9H) as TPT in PWH. All included participants were on suppressive antiretroviral therapy and had available TST or IGRA results at study entry. Samples collected at week 0 (pre-TPT) and week 48 (post-TPT) were analyzed. Monocyte subset and activation markers were measured using multiparameter flow cytometry. Proinflammatory cytokines (IL-6 and TNF-α) were assessed after 6-hour lipopolysaccharide (LPS) stimulation. Linear regression models were used for primary comparisons of monocyte markers by TST/IGRA status, adjusted for age, sex, country, and CD4 count.
RESULTS: In adjusted models, compared with TST/IGRA-negative participants (n = 27), TST/IGRA-positive participants (n = 30) had ∼2-fold relative increases in the median fluorescence intensity of CD64 (unstimulated) and CCR2 (post-LPS) on total monocytes and across monocyte subsets, pre- and post-TPT. Among TST/IGRA-positive participants, 1HP was associated with decreased fold changes over time for the percentage of CCR2+ monocytes and blunted IL-6/TNF-α responses compared with 9H.
CONCLUSIONS: PWH with a positive TST or IGRA exhibited signals of monocyte activation pre- and post-TPT. TPT with 1HP led to blunted proinflammatory monocyte changes compared with 9H.