Virological outcomes and metabolic effects after switching from ritonavir-boosted protease inhibitors to a dolutegravir-based regimen in virologically suppressed patients living with HIV.

Abstract

A ritonavir-boosted protease inhibitor (PI)-based antiretroviral therapy (ART) regimen can cause abnormal lipid levels and increased incidence of cardiovascular disease. Switching to a dolutegravir (DTG)-based regimen has been shown to improve blood lipid levels, but data in the Thai population are limited. A prospective cohort study was conducted at Srinagarind Hospital between April 28, 2021, and April 30, 2022. Patients were eligible if they (1) were over 18years of age, 2) had received a ritonavir-boosted PI-based regimen for at least three months, and 3) had documented plasma HIV RNA levels below 50copies/mL within six months before the enrollment. All eligible patients included in the study switched from a ritonavir-boosted PI-based ART regimen to a DTG-based regimen. The primary outcome was changes in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 24. Forty-six eligible patients were enrolled, 71.7% of whom were male, with a mean age of 49.4years. Mean body weight was 62.7kg and body mass index (BMI) was 22.86kg/m2. The majority of patients had been on a regimen of boosted atazanavir (ATV/r; 60.9%), followed by boosted lopinavir (LPV/r; 37.0%). Six patients were withdrawn from the study. At week 24 after switching to DTG, LDL-C was significantly lower than at baseline, with a difference of -15.1mg/dL (95% confidence interval [CI; -23.3 to -6.8]; p-value < 0.001), as were total cholesterol and triglycerides, with differences of -22.1mg/dL (95% CI [-33.3 to -10.8]; p-value <0.001) and -67.7mg/dL, (95% CI [-88.3 to -47.0]; p-value 0.001), respectively. There were no significant changes in body weight (0.51kg; 95% CI [-0.37 to 1.38]; p-value 0.251) or BMI (0.17kg/m2; 95% CI [-0.14 to 0.48]; p-value 0.284) from baseline to week 24. In addition, 39 of 40 patients (97.5%) maintained virological suppression (HIV RNA <50copies/mL), with only one patient (2.5%) developing virological failure. Three grade 3 adverse events were observed. Switching from a boosted PI-based ART regimen to a DTG-based regimen in people living with HIV/AIDS who had attained prior virological suppression resulted in a significant reduction in total cholesterol, LDL-C, and triglyceride levels, but did not increase the patient's body weight at 24weeks of follow-up. Furthermore, the DTG-based regimen was also highly effective in maintaining virological suppression. Thai Clinical Trials Registry, TCTR20210625004.