Efficacy and Safety of Low-Dose Colchicine on Surrogate Markers of Cardiovascular Events in People Living With HIV Receiving Antiretroviral Therapy

Trial Designs This is a single-center, randomized, double-blind, controlled study comparing the effect of low-dose colchicine to inflammatory markers at 12-week follow-up with placebo. The study protocol had been reviewed and approved by the Ethical Committee of Human Rights Related to Research Involving Human Subjects, Faculty of Medicine Ramathibodi Hospital, Mahidol University (ethical committee approval number MURA2020/762), and our trial was conducted following the principles of good clinical practice and the Declaration of Helsinki.

Patient Enrollment PLWH aged more than 30 years old and were receiving tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV), tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV), tenofovir/lamivudine/rilpivirine (TDF/3TC/RPV), tenofovir/lamivudine/dolutegravir (TDF/3TC/DTG) or abacavir/lamivudine/efavirenz (ABC/3TC/EFV) for at least six months were enrolled. The patients were eligible for study entry if the hs-CRP level was more than or equal 2 mg/L, the CD4 level was more than or equal 300 cells/mm3, suppressed HIV viral load, estimated glomerular filtration rate (eGFR) above 30 ml/min/1.73 m2, and they were able to follow-up as protocol.

The exclusion criteria were chronic kidney disease stage 4 and 5 (eGFR less than 30 ml/min/1.73 m2), liver cirrhosis (Child-Pugh class B or C), previous evidence of coronary artery disease, or cerebrovascular event, and indications or contraindications to colchicine. Patients were excluded during the study if they had a recent infection within one month or at least grade 3 adverse events or had indication to use other medication interacted with colchicine.

Study Objectives The primary objective was to compare the mean difference of hs-CRP, interleukin-6 levels, and interleukin-1 receptor antagonist from baseline to the 12-week and 24-week follow-up between patients receiving low-dose colchicine and placebo. The secondary objective was to assess safety outcomes of the low-dose colchicine, e.g., myositis, agranulocytosis, gastrointestinal side effects, infection.

Trial Conduction This study was conducted at Ramathibodi Hospital (Bangkok, Thailand) from May 2020 to April 2021. Participants were recruited from the outpatient department (infectious disease clinic) at Ramathibodi Hospital, Bangkok, Thailand. All participants were evaluated for eligibility before randomization and follow-up. All patients gave written informed consent before initiation of the protocol.