Lipid changes on Protease Inhibitors in South Africa: a retrospective cross-sectional analysis comparing metabolic profiles and lipid management in patients living with HIV on different protease inhibitors at Charlotte Maxeke Johannesburg Academic Hospital

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Background People living with HIV (PLWH) are at risk of cardiovascular (CV) disease, with few studies having assessed CV risk in Southern Africa. Protease inhibitors (PIs) are known to cause dyslipidaemia, in particular, lopinavir more so than darunavir. The WRHI 052 study by Venter et al, a randomised parallel-group open label non-inferiority phase 3 trial, at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), demonstrated that low dose darunavir/ritonavir (400 mg/ 100 mg) sustained viral load suppression equivalently to lopinavir/ritonavir (800 mg/ 200 mg). This could be a costeffective option with improved metabolic effects. Objective: To assess CV risk screening in PLWH receiving two different PI based antiretroviral therapy (ART) regimens and exploring the difference in the metabolic profiles between the two PI groups. Methods: A retrospective sub-analysis of the WRHI 052 study. Between June 30 2016, and June 15 2017, 300 PLWH on a lopinavir/ritonavir regimen were randomized into two groups, 152 continued the lopinavir/ritonavir combination and 148 were switched to darunavir/ritonavir. The metabolic parameters of the two PI arms were compared at 24 and 48 weeks. A 2-year post study completion retrospective analysis was performed at the CMJAH HIV clinic where routine care was continued. An analysis of CV risk using the Framingham CV risk score, lipid management and achievement of low-density lipoprotein cholesterol (LDLC) goals was performed. Results: In the darunavir/ritonavir group, a significant decrease in total cholesterol (TC) of 7.7% at 48 weeks (95% CI, p<0.001 was observed, and the TC/HDLC ratio declined at 24 and 48 weeks by 1.7% and 3.9% respectively (95% CI, p=0.09; p=0.99). The TC increased by 0.4% at 48 weeks in the lopinavir/ritonavir group (95% CI, p=0.01) and the TC/HDLC ratio increased by 3.3% and 0.9% at 24 and 48 weeks (95%CI, p=0.04 and p=0.12). There was no statistical significance between the median differences and median percentage difference in TC/HDLC ratios between PI groups. LDLC decreased significantly in both PI groups at 24 and 48 weeks, however there was no statistical significance between PI groups. Weight and consequently body mass index (BMI) increased over time with a consistent trend in both groups and genders. Due to weight gain, the percentage of participants with a normal BMI declined from 41.5% at baseline to 33% and 35% at 24 and 48 weeks. Eighty-three percent of all participants had dyslipidaemia with 22% receiving lipid lowering therapy. Eighty-five percent of all participants had a low Framingham CV risk score with 52% achieving target LDLC. Conclusion TC and TC/HDLC ratio improved when switched to darunavir/ritonavir. Significant weight gain was observed in participants on a PI over time. Longitudinal studies on weight gain in individuals on PIs are warranted. Increased awareness and assessment of CV risk is needed.
A research report submitted in partial fulfilment of the requirement for the degree of Master of Medicine (MMed) in Internal Medicine to the Faculty of Health Sciences, University of the Witwatersrand, School of Clinical Medicine, Johannesburg, 2023
Protease inhibitors, Lipid changes, Antiretroviral therapy (ART)