Dyslipidemia and statin use in people with HIV-1 infection: beyond the lipid-lowering effect.

Aims: Advances in antiretroviral therapy have transformed HIV-1 infection into a chronic condition, enabling people living with HIV-1 (PWH) to achieve life expectancies comparable to those of the uninfected population. Consequently, a range of co-morbidities, particularly an increased incidence of cardiovascular events, has becoming more evident. Among these, dyslipidemia stands out as a significant risk factor with a multifactorial pathogenesis. The aim of this narrative review is to highlight the multifactorial origins of dyslipidemia in PWH, to provide an overview of drug interactions between statins and antiretroviral therapy, and examine the unique anti-inflammatory and immunomodulatory properties of statins in this context.

Data synthesis: Some studies indicate a reduction of mortality and cardiovascular risk in PWH treated with statins. However, the benefit of statin therapy is variable and seems to be dependent on HIV-1 length exposure and type of antiretroviral drugs and seems to be lower in individuals without comorbidities or additional risk factors. Statins are often underdosed for the perceived risk of drug interactions. Beyond their lipid-lowering effects, statins exert additional benefits, including anti-inflammatory and immunomodulatory actions on vascular tissues, monocyte-macrophages, and lymphocytes. These effects have sparked interest in their potential applications beyond dyslipidemia treatment.

Conclusions: Statins may provide a clinical benefit in PWH by lowering LDL cholesterol and modulating immunity and inflammation. However, there is a clinical need for HIV-1-specific LDL cholesterol targets given the excess cardiovascular risk in this population, as well as for the identification of high-risk subgroups that may benefit most from statin treatment.