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Dolutegravir-associated hyperglycemia: a narrative review.
Allan Buzibye1, Barbara Castelnuovo2, Robert C Bollinger3
1Infectious Diseases Institute, Makerere University College of Health Sciences, P.O.BOX 22418, Kampala, Uganda. abuzibye@idi.co.ug.
AIDS Research and Therapy
|September 27, 2025
Summary
Dolutegravir, a preferred HIV drug, is linked to increased hyperglycemia in sub-Saharan Africa. Potential causes include mitochondrial issues, magnesium chelation, and inflammation, impacting insulin resistance.
Area of Science:
- Infectious Diseases
- Endocrinology
- Pharmacology
Background:
- Dolutegravir is a preferred antiretroviral (ARV) drug for HIV treatment due to its high resistance barrier and efficacy.
- However, increased rates of hyperglycemia have been reported in individuals living with HIV (PLWHIV) in sub-Saharan Africa receiving dolutegravir-based regimens.
- This necessitates an investigation into the potential mechanisms linking dolutegravir to hyperglycemia.
Purpose of the Study:
- To review and synthesize the current understanding of dolutegravir-associated hyperglycemia.
- To explore potential biological mechanisms contributing to this adverse effect.
- To highlight factors influencing hyperglycemia variability in PLWHIV on dolutegravir.
Main Methods:
- This study is a narrative review of existing literature.
- It synthesizes findings on dolutegravir, hyperglycemia, and related biological pathways.
- The review considers factors such as prior antiretroviral therapy, genetics, and lifestyle.
Main Results:
- Potential mechanisms for dolutegravir-associated hyperglycemia include mitochondrial dysfunction (potentially exacerbated by prior NRTI use), magnesium chelation by dolutegravir, and chronic inflammation.
- Elevated pro-inflammatory markers (IL-6, CRP, TNF-α) may contribute to insulin resistance.
- Hyperglycemia prevalence and severity vary among patients due to genetic, lifestyle, and treatment history factors.
Conclusions:
- Dolutegravir's association with hyperglycemia is a growing concern, particularly in specific populations.
- While multiple mechanisms are proposed, insulin resistance appears significant, though the precise contribution to reduced insulin release versus impaired insulin action requires further clarification.
- Further research is needed to elucidate the exact pathophysiology and guide clinical management of dolutegravir-associated hyperglycemia.
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