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<p>Dolutegravir is a preferred antiretroviral drug given its high resistance barrier and efficacy; however, reports from sub-Saharan Africa indicate increased hyperglycemia rates among individuals living with HIV on dolutegravir. Potential mechanisms include mitochondrial dysfunction from previous exposure to NRTIs like stavudine and zidovudine, which causes mitochondrial toxicity and predisposes patients to hyperglycemia upon switching to dolutegravir; magnesium chelation, which is borrowed from dolutegravir’s mode of action (dolutegravir inhibits the action of integrase by chelation of magnesium required as a cofactor by the HIV enzyme); and chronic inflammation, with elevated pro-inflammatory markers like IL-6, CRP, and TNF-α contributing to insulin resistance. The narrative review highlights variability in hyperglycemia among patients, influenced by genetics, lifestyle, and prior antiretroviral therapy. The exact nature of dolutegravir-associated hyperglycemia, whether due to insulin resistance or reduced insulin release, remains unclear, although insulin resistance is significant.</p>

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Dolutegravir-associated hyperglycemia: a narrative review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月26日

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  • Allan Buzibye,
  • Barbara Castelnuovo,
  • Robert C. Bollinger,
  • Joseph Ssebulime,
  • Denis Omali,
  • Daniel Muller,
  • Frank Mulindwa,
  • Eva Laker,
  • Catriona Waitt,
  • Irene Andia,
  • Mohammed Lamorde,
  • Ahmet Hoke,
  • Bernard S. Bagaya,
  • Yukari C. Manabe

摘要

Dolutegravir is a preferred antiretroviral drug given its high resistance barrier and efficacy; however, reports from sub-Saharan Africa indicate increased hyperglycemia rates among individuals living with HIV on dolutegravir. Potential mechanisms include mitochondrial dysfunction from previous exposure to NRTIs like stavudine and zidovudine, which causes mitochondrial toxicity and predisposes patients to hyperglycemia upon switching to dolutegravir; magnesium chelation, which is borrowed from dolutegravir’s mode of action (dolutegravir inhibits the action of integrase by chelation of magnesium required as a cofactor by the HIV enzyme); and chronic inflammation, with elevated pro-inflammatory markers like IL-6, CRP, and TNF-α contributing to insulin resistance. The narrative review highlights variability in hyperglycemia among patients, influenced by genetics, lifestyle, and prior antiretroviral therapy. The exact nature of dolutegravir-associated hyperglycemia, whether due to insulin resistance or reduced insulin release, remains unclear, although insulin resistance is significant.