Effect of atorvastatin on subclinical atherosclerosis in virally-suppressed HIV-infected patients with CMV seropositivity: a randomized double-blind placebo-controlled trial

Evy Yunihastuti,Mutiara Shinta Noviar,Muhammad Syahrir Azizi,Dyah Purnamasari,Sally Aman Nasution,Chyntia Olivia Maurine Jasirwan,Riwanti Estiasari,Endah Ayu T Wulandari,Lusiani Rusdi

doi:10.12688/f1000research.28262.1

Evy Yunihastuti, Mutiara Shinta Noviar + Show 7 more

Open Access

https://doi.org/10.12688/f1000research.28262.1

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Abstract

Background: Persistent immune activation and inflammation in HIV-infection are linked to excess cardiovascular risk and other non-communicable diseases. Periodic asymptomatic CMV-reactivity in HIV infected patients over a lifetime may contribute to non-AIDS defining morbidity. Despite undetectable levels of HIV and CMV, these patients continue to have increased levels of biomarkers and immune activations. Statin administration is thought to reduce subclinical atherosclerosis by decreasing LDL-C levels. It may also add beneficial effects against CMV infection. Methods: We are conducting a double-blind placebo-controlled trial in which patients are randomized to receive either atorvastatin or placebo with a ratio of 1:1. This trial aims to study the effect of atorvastatin in statin-naive virally-suppressed HIV-infected patients with stable ART and CMV seropositivity on carotid intima media thickness (CIMT), tool that evaluates subclinical atherosclerosis. The study recruits 80 patients at HIV integrated care unit of Cipto Mangunkusumo hospital. All eligible subjects have CIMT evaluation as primary outcome, along with flow mediated vasodilatation (FMD), liver fibrosis and steatosis evaluation, fasting lipid, neurocognitive test, community periodontal index (CPI), and residual immune activation as secondary outcomes in 48 weeks. Ethics and dissemination: This study has received an ethical approval from Health Research Ethics Commitee–Universitas Indonesia and Cipto Mangunkusumo Hospital. Before joining the study, all participants fill in an informed consent form. At the end of study analysis, the trial results will be published and disseminated in peer-reviewed journals. Discussion: The main purpose of our study is to evaluate the effect of atorvastatin administration on CIMT changes in statin naïve virally suppressed HIV-infected patients with stable ART and CMV seropositivity Registration: ClinicalTrials.gov ID NCT04101136; registered on 24 September 2019.

Highlights

Active antiretroviral therapy (HAART) has contributed to significant reduction in AIDS related morbidity and mortality in HIV-infected patients[1]
A small study conducted by Lebech AM et al revealed no significant difference between FMD value among HIV-infected patients with a low cerebrovascular disease (CVD) risk compared to controls[15]
Other aims are to evaluate the interaction between baseline CMV copy number and the effect of atorvastatin on carotid intima media thickness (CIMT) changes, the effect of 48 weeks of 20 mg daily atorvastatin versus placebo on fasting lipid changes, the effect on liver fibrosis and steatosis changes, neurocognitive changes, several immune activation biomarker changes, CPI changes in virally suppressed HIV patients with CMV seropositivity, and to evaluate the interaction between baseline CMV copy number and effect of atorvastatin on FMD, neurocognitive function, liver fibrosis and steatosis, lipid profile, and immune activation biomarkers changes in 48 weeks

Summary

Introduction

Active antiretroviral therapy (HAART) has contributed to significant reduction in AIDS related morbidity and mortality in HIV-infected patients[1]. Cardiovascular disease and other NCDs are associated with persistent inflammation and chronic activation that are still ongoing even in the state of viral suppression[2]. Periodic asymptomatic CMV-reactivity in HIV-infected patients over a lifetime may play a part in non-AIDS defining morbidity, including cardiovascular disease, neurocognitive impairment, renal disease, and cancer[6]. Statin administration is thought to reduce subclinical atherosclerosis by decreasing LDL-C levels It may add beneficial effects against CMV infection. Methods: We are conducting a double-blind placebo-controlled trial in which patients are randomized to receive either atorvastatin or placebo with a ratio of 1:1 This trial aims to study the effect of atorvastatin in statin-naive virally-suppressed HIV-infected patients with stable ART and CMV seropositivity on carotid intima media thickness (CIMT), tool that evaluates subclinical atherosclerosis. All eligible subjects have CIMT evaluation as article can be found at the end of the article

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