Abstract
Objective: To determine whether pitavastatin reduces enterocyte injury, assessed by intestinal fatty acid-binding protein (I-FABP), among antiretroviral therapy-treated people with HIV (PWH) enrolled in the REPRIEVE mechanistic substudy.
Design: Randomized, double-blind, placebo-controlled trial.
Methods: We analyzed fasting plasma I-FABP at entry and month 24 among participants randomized to pitavastatin 4 mg daily or placebo. Baseline characteristics were summarized across I-FABP quartiles. Associations between entry I-FABP and inflammatory and immune activation biomarkers were assessed using Spearman correlations. Longitudinal changes were evaluated using intention-to-treat and per protocol analyses and generalized estimating equation models.
Results: Among 710 participants with entry I-FABP measurements (median age 50 years; 18.5% female; 98% with undetectable viral load), median I-FABP levels were 2690 [Q1, Q3: 1888, 3770] (pg/mL). Entry I-FABP correlated modestly with markers of systemic inflammation and monocyte activation, including GDF-15 and soluble CD14. Over 24 months, I-FABP levels declined similarly in the pitavastatin and placebo arms, with no significant differences in absolute or fold change.
Conclusions: In this well-treated HIV cohort, higher baseline I-FABP levels were associated with increased inflammatory markers at study entry. However, pitavastatin did not reduce I FABP over follow-up. These findings suggest that the cardiovascular benefit of pitavastatin in REPRIEVE is unlikely to be mediated through reductions in enterocyte injury, although gut-barrier effects of other statins cannot be excluded.