Department of Medicine

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Browsing Department of Medicine by Subject "Adipose tissues – Health"

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    The effect of dolutegravir on adipose tissue health
    (Stellenbosch : Stellenbosch University, 2022-10) Coetzee, Johanna Adriana; Smith, Carine; Ross, Kelly Shirley; Faculty of Medicine and Health Sciences. Dept. of Medicine. Division of Clinical Pharmacology.
    ENGLISH ABSTRACT: Introduction: Dolutegravir, an integrase strand transfer inhibitor (INSTI), forms part of the first-line antiretroviral (ARV) therapy. Despite low cost, fewer drug-drug interactions and minimal reported side effects, dolutegravir use has clinically been associated with weight gain. The significance of this in terms of adipose- and overall patient health remains to be fully elucidated. Methods: The effects of dolutegravir on the adipose tissue health were assessed in a 12-week treatment intervention study in Wistar rats, allowing an assessment of risk profile for dolutegravir in the absence of potential confounding effects of retroviral infection or other ARV agents commonly found in combination therapy. Dolutegravir was administered as a human equivalent dose set in jelly blocks, once daily for 12 weeks, starting at 8 weeks of age. Visceral adipose tissue morphology and fibrosis profile, adipokine and inflammatory cytokine levels were assessed. Results: Dolutegravir did not change the rate of body mass increase in the rats (when compared to a placebo group). Females presented to have smaller adipocyte size and increased adiponectin secretion – more pronounced in the treated group compared to the controls. While pro-inflammatory cytokines (TNF-α and MCP-1) were also elevated in both the female groups compared to the males. Conclusion: Current data illustrates that in terms of potential effects of dolutegravir on AT health, females seem more vulnerable to undesired longer term outcome. The overall small effect sizes seen is in line with a chronic, low-grade dysregulation which may predispose dolutegravir-treated patients to development of co-morbidities with a chronic inflammatory character.