review · SAGE Open Medicine
Dolutegravir is recommended by the World Health Organization as the preferred first-line and second-line treatment for human immunodeficiency virus across all patient populations. Despite its broad adoption, excessive weight gain linked to dolutegravir-based regimens has emerged as a growing clinical concern with unclear long-term consequences. This weight gain is linked to an increased incidence of hyperglycaemia, hypertension, metabolic syndrome, and elevated cardiovascular risks. Patients also show greater adipocyte differentiation and elevated expression of markers associated with lipid storage. The biological mechanisms behind these changes remain unconfirmed. Hypothesised pathways include dolutegravir interfering with central nervous system appetite regulation via the melanocortin-4 receptor, disruption of insulin signalling, and enhanced penetration into adipose tissue resulting in adipogenesis, tissue fibrosis, and local insulin resistance.
Millions of people worldwide rely on dolutegravir to control HIV infection. When an essential life-saving medication triggers substantial weight gain and secondary metabolic disorders such as diabetes and cardiovascular disease, it threatens patients' overall health outcomes. Defining how these side effects occur is necessary to help healthcare providers anticipate, manage, or mitigate long-term treatment risks.
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Dolutegravir is an integrase inhibitor and is recommended by the World Health Organization as the preferred first-line and second-line human immunodeficiency virus treatment in all populations. Excessive weight gain associated with dolutegravir-based regimens is an emerging issue; however, the long-term metabolic consequences of this effect have not been fully understood. Growing evidence shows that this leads to a higher incidence of hyperglycemia, hypertension, and metabolic syndrome, along with elevated cardiovascular risk. Dolutegravir-based regimens, also associated with greater adipocyte differentiation and greater expression of markers associated with lipid storage, continue to be a problem among patients living with human immunodeficiency virus. The mechanisms by which certain antiretroviral therapy agents differentially contribute to weight gain remain unknown. Some clinical investigators speculate that dolutegravir could interfere with central nervous system appetite regulation (melanocortin-4 receptor) and insulin signaling, or may have better penetration of adipose tissue where they could exert a direct impact on adipose tissue adipogenesis, fibrosis, and insulin resistance. This review summarizes our current understanding of weight gain and fat changes associated with dolutegravir and its possible secondary metabolic comorbidities.
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DOI: 10.1177/20503121241260613
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