Inhibition of Th1-type immune responses in persons with HIV with current statin exposure

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.

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.

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.

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.