Effectiveness and safety of statins on outcomes in patients with HIV infection: a systematic review and meta-analysis

Abstract

Statins are hypolipidaemic in human immunodeficiency virus (HIV) positive individuals. However, their effect on all-cause mortality and rate of discontinuation is unclear. We conducted a systematic review to evaluate the impact of statins on all-cause mortality, discontinuation rates, and risk of adverse effects among HIV patients on highly active antiretroviral therapy (HAART). We searched four electronic databases from inception until October 2021 for trials and cohort studies evaluating the effects of statin treatment versus placebo in HIV patients. Forty-seven studies involving 91,594 patients were included. Statins were associated with significantly lower risk of discontinuation (RR, 0.701; 95% CI 0.508–0.967; p = 0.031). The risk of all-cause mortality (RR, 0.994; 95% CI 0.561–1.588; p = 0.827), any adverse effects (RR, 0.780; 95% CI 0.564–1.077; p = 0.131) and, diabetes mellitus (RR, 0.272; 95% CI 0.031–2.393; p = 0.241) with statin treatment were lower but not statistically significant compared to placebo/control. Statin treatment was associated with a trend of higher but statistically insignificant risk of myalgia (RR, 1.341; 95% CI 0.770–2.333; p = 0.299), elevated creatine kinase (RR, 1.101; 95% CI 0.457–2.651; p = 0.830) and liver enzyme activities (RR, 1.709; 95% CI 0.605–4.831; p = 0.312). Clinicians should consider the nocebo effect in the effective management of PLWH on statins, who present with common adverse effects such as myalgia and, elevated levels of creatine kinase and liver enzymes.

Achievement of Primary Prevention Cardiometabolic Targets in Women with HIV: An Urgent Call to Action to Pursue Cardiovascular Health

“…Healthcare providers must consider the potential impact of the nocebo effect and fear when prescribing statins to PLWH, as these factors may contribute to the occurrence of adverse effects and statin discontinuation. In a comprehensive systematic review and meta-analysis including 91,594 PLWH and assessing major outcomes associated with statin treatment, the risk of all-cause mortality, any adverse effects, and the development of diabetes mellitus was significantly lower in the group receiving statins [ 45 ]. Additionally, prevalent symptoms in PLWH, including asthenia, elevated liver enzyme levels, increased CPK, and myalgia, were noted, but they were not statistically associated with statin use [ 45 , 46 , 47 ].…”

Effects of statins beyond lipid-lowering agents in ART-treated HIV infection

“…In 2019, the scientific committee of American Heart Association recommended preventive therapy among PWH with elevated CVD risk profile including presence of HIV-associated and/or more general factors such as a positive family history and chronic kidney disease ( 89 ). While REPRIEVE data strongly support statin use; others concluded a lower but non-significant decrease in the risk of all-cause mortality, any adverse effect and DM with statin treatment versus placebo/control ( 54 , 90 ). Of note, study by Phan et al.…”

A Systematic Review and Meta-Analysis on the Impact of Statin Treatment in HIV Patients on Antiretroviral Therapy

“…Therefore, all these concerns make us question whether statins are safe for PLHIV taking ART. We have noted a few literature reviews that evaluated data on the beneficial effects of statins against secondary complications in PLHIV [30][31][32]; however, the impact on surrogate markers of HIV infections and cholesterol is inconsistent. Therefore, the current meta-analysis sought to evaluate whether statin treatment in HIV patients improves or worsens the surrogate markers of HIV infection, focusing on CD4 count, viral load and markers of immune activation.…”