Effect of SLCO1B1 c.521T>C polymorphism on the lipid response to statins in people living with HIV on a boosted protease inhibitor containing regimen.

Marzolini, Catia; Cavassini, Matthias; Braun, Dominique L; Hachfeld, Anna; Bernasconi, Enos; Calmy, Alexandra; Schmid, Patrick; Battegay, Manuel; Elzi, Luigia (2023). Effect of SLCO1B1 c.521T>C polymorphism on the lipid response to statins in people living with HIV on a boosted protease inhibitor containing regimen. British journal of clinical pharmacology, 89(9), pp. 2739-2746. Wiley-Blackwell 10.1111/bcp.15754

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AIM

We previously observed that some individuals on HIV boosted protease inhibitor containing regimen do not achieve their lipid targets despite elevated statin concentrations. This study evaluated whether the common single polymorphism c.521T>C in SLCO1B1, associated with reduced statin uptake in the liver, could explain this observation.

METHODS

People living with HIV (PLWH) in the Swiss HIV Cohort Study were eligible if they were on a boosted protease inhibitor concomitantly with a statin for at least 6 months and if their SLCO1B1 genotype was available. Furthermore, their lipids had to be documented before and after the introduction of the statin. The statin efficacy was defined as % change in total-, LDL-, HDL-cholesterol and triglycerides levels after statin initiation compared to pre-treatment levels. Lipid response was adjusted for differences in potency and dose between statins.

RESULTS

88 PWH were included, of whom 58, 28 and 2 carried the SLCO1B1 TT, TC and CC genotypes, respectively. The change in lipid levels after statin initiation tended to be lower in carriers of the polymorphism although the difference was not statistically significant (TT vs TC/CC: total-: -11.7% vs -4.8%; LDL-: -20.6% vs -7.4%; HDL-cholesterol: 1.6% vs 0; triglycerides: -11.5% vs -7.9%). In the multiple linear regression, change in total cholesterol was inversely correlated with the total cholesterol level pre-statin treatment (coefficient -6.60, 95%CI: -9.63 to -3.56, p<0.001).

CONCLUSIONS

The lipid lowering effect of statins tended to be attenuated by SLCO1B1 polymorphism and progressively declined as total cholesterol under the boosted protease inhibitor treatment decreased.

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