Background
Persistent inflammation is common in people living with HIV (PLWH) despite suppressive antiretroviral therapy (ART). Lauric acid (LA), a medium-chain dietary fatty acid, may enhance immune recovery and reduce inflammation.
Methods
In a randomized, placebo-controlled clinical trial, 45 PLWH on stable ART received daily oral 3g LA (n=15), 1.5g LA (n=15) or placebo (n=15) for 24 weeks, followed by 24 weeks of follow-up. Primary endpoints included tolerance, HIV reservoir measures (total/intact HIV-DNA, intracellular HIV-RNA), lymphocyte counts, systemic inflammation indexes (NLR, PLR, SII), and plasma cytokines at weeks 4, 12, 24, 36, and 48. Friedman and mixed-effects regression models (Wald test) were used for analysis.
Results
Of 45 enrolled participants, 42 completed the study; 34 were male, median age 49 y, median CD4⁺ T-cell count 815 cells/µL. Seven mild treatment-related adverse events occurred (gastrointestinal: 3 in 1.5g, 3 in 3g, 1 in placebo), none requiring discontinuation. No severe adverse events or lab abnormalities were observed. At week 24, treatment with 3g LA was associated with significant expansions in CD4⁺ T cells (median +110 cells/µL, p = 0.019; Figure 1A ), and CD8⁺ T cells (median +110 cells/µL, p = 0.029), a reduction in neutrophils (median −970 cells/µL, p = 0.020), and significant decreases in SII (median −170, p = 0.001), PLR (median −23, p = 0.040), and NLR (median −0.81, p = 0.0003). All these effects persisted after LA discontinuation (weeks 36 and 48). At week 24, cytokine profiling revealed a shift from pro-inflammatory signaling (CXCL9 ↓ p = 0.09; OSM ↓ p = 0.05) to regenerative signaling (EGF ↑ p = 0.03). After LA discontinuation, cytokines shifted toward antiviral/Th1-driven responses (CXCL9 p=0.005, CXCL10 p=0.0012, TRAIL p=0.005, CCL19 p=0.003, and LTA p=0.05) while maintaining tissue-regenerative profiles (TGFA p=0.03, HGF p=0.018, and EGF p=0.01). Furthermore, reductions were observed in total HIV DNA (week 24: FC = 2.41, p = 0.049; week 48: FC = 2.55, p = 0.037), intact HIV DNA (week 48: FC = 3.04, p = 0.043; Figure 1B), and intracellular HIV RNA (week 48: FC = 3.84, p = 0.029).
Conclusions
LA supplementation was safe, well tolerated, enhanced CD4⁺ and CD8⁺ T-cell recovery, reduced systemic inflammation, and decreased HIV reservoir measures, supporting further evaluation as an adjunctive strategy against persistent inflammation and HIV persistence.
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