AIDS (London, England) · 2025
Inhibition of Th1-type immune responses in persons with HIV with current statin exposure.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Knudsen Andreas Dehlbæk, Gelpi Marco, Suarez-Zdunek Moises A, Loft Josefine A, Ueland Per Magne, Ostrowski Sisse Rye, Midttun Øivind, Martinez Esteban, Nielsen Susanne Dam
Аннотация
BACKGROUND: Recent findings from the REPRIEVE study suggest statins provide greater cardiovascular protection in persons with HIV (PWH) than expected from low-density lipoprotein (LDL) cholesterol reduction alone. Statins may modulate Th1-type immune responses, including interferon-gamma (IFN-γ), neopterin, and kynurenine metabolism. We investigated if statin use in PWH was associated with suppression of Th1-type immune responses.
METHODS: This cross-sectional study included PWH from the Copenhagen Comorbidity in HIV infection (COCOMO) study. Demographic and clinical variables were collected through questionnaires and physical examinations. Plasma IFN-γ, neopterin, kynurenine-to-tryptophan ratio [marker of indoleamine 2,3-dioxygenase (IDO)-1 activity], interleukin (IL)-6, IL-1β, soluble CD14, and clinical data were measured in plasma. Multivariable logistic regression models were adjusted for age, sex, waist-to-hip ratio, metabolic syndrome, physical activity, high-sensitivity C-reactive protein, and LDL cholesterol.
RESULTS: We included 1041 of whom 130 (12.5%) received statins. Statin-treated PWH were older (60 vs. 49 years), and more frequently men (92 vs. 84%). In unadjusted analyses, odds of elevated markers of Th1 immune responses did not differ significantly between groups. After multivariable adjustment, statin exposure was associated with lower odds of high kynurenine-to-tryptophan ratio [odds ratio (OR): 0.60; 95% confidence interval (CI) 0.37-0.98], IFN-γ (OR 0.58; 95% CI 0.36-0.92), and neopterin (OR 0.58; 95% CI 0.36-0.92). No significant associations were observed for IL-6, IL-1β, or soluble CD14.
CONCLUSION: In PWH, statin therapy was independently associated with suppression of Th1-type immune responses. These findings support a lipid-independent, immunomodulatory mechanism by which statins may confer cardiovascular protection in HIV infection and warrant confirmation in prospective studies.
METHODS: This cross-sectional study included PWH from the Copenhagen Comorbidity in HIV infection (COCOMO) study. Demographic and clinical variables were collected through questionnaires and physical examinations. Plasma IFN-γ, neopterin, kynurenine-to-tryptophan ratio [marker of indoleamine 2,3-dioxygenase (IDO)-1 activity], interleukin (IL)-6, IL-1β, soluble CD14, and clinical data were measured in plasma. Multivariable logistic regression models were adjusted for age, sex, waist-to-hip ratio, metabolic syndrome, physical activity, high-sensitivity C-reactive protein, and LDL cholesterol.
RESULTS: We included 1041 of whom 130 (12.5%) received statins. Statin-treated PWH were older (60 vs. 49 years), and more frequently men (92 vs. 84%). In unadjusted analyses, odds of elevated markers of Th1 immune responses did not differ significantly between groups. After multivariable adjustment, statin exposure was associated with lower odds of high kynurenine-to-tryptophan ratio [odds ratio (OR): 0.60; 95% confidence interval (CI) 0.37-0.98], IFN-γ (OR 0.58; 95% CI 0.36-0.92), and neopterin (OR 0.58; 95% CI 0.36-0.92). No significant associations were observed for IL-6, IL-1β, or soluble CD14.
CONCLUSION: In PWH, statin therapy was independently associated with suppression of Th1-type immune responses. These findings support a lipid-independent, immunomodulatory mechanism by which statins may confer cardiovascular protection in HIV infection and warrant confirmation in prospective studies.