Switching from boosted PIs to dolutegravir decreases soluble CD14 and adiponectin in high cardiovascular risk people living with HIV

BACKGROUND: Switching from boosted PIs to dolutegravir in people living with HIV (PLWH) with high cardiovascular risk improved plasma lipids at 48 weeks in the NEAT022 trial. Whether this strategy may have an impact on cardiovascular biomarkers is unknown. METHODS: We assessed 48 week changes in biomarkers associated with inflammation, endothelial dysfunction, monocyte immune activation, oxidation, insulin resistance, hypercoagulability, heart failure, myocardial injury, and glomerular and tubular kidney injury. RESULTS: Of 415 PLWH randomized in the NEAT022 study, 313 (75.4%) remained on allocated therapy and had paired samples available. Soluble CD14 (-11%, P < 0.001) and adiponectin (-11%, P < 0.001) significantly declined and high-sensitive C-reactive protein (-13%, P = 0.069) and oxidized LDL (-13%, P = 0.084) tended to decrease with dolutegravir. Switching to dolutegravir remained significantly associated with soluble CD14 and adiponectin reductions after adjustment for baseline variables. There were inverse correlations between soluble CD14 and CD4 count changes (P = 0.05), and between adiponectin and BMI changes (P < 0.001). CONCLUSIONS: Switching from boosted PIs to dolutegravir in PLWH with high cardiovascular risk led to soluble CD14 and adiponectin reductions at 48 weeks. While decreasing soluble CD14 may entail favourable health effects in PLWH, adiponectin reduction may reflect less insulin sensitivity associated with weight gain.