INSTI Adverse Effects — RACP Adult Medicine MCQ

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ModerateInfectious DiseasesINSTI Adverse EffectsRACP Adult Medicine

A 45-year-old man with HIV on dolutegravir/lamivudine/tenofovir alafenamide has an undetectable viral load and CD4 of 650. He develops new-onset insomnia, weight gain of 8 kg, and elevated blood glucose (HbA1c 51 mmol/mol). Which antiretroviral is most likely contributing?

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Correct answer: D — Dolutegravir

Dolutegravir (and other integrase strand transfer inhibitors – INSTIs) is increasingly recognised as causing weight gain (average 3–5 kg), neuropsychiatric effects (insomnia, depression), and metabolic effects (insulin resistance, diabetes). The ADVANCE and NAMSAL trials highlighted INSTI-associated weight gain, particularly in women and people of African descent. Neuropsychiatric effects are more common with dolutegravir than other INSTIs (bictegravir may have fewer). If side effects are intolerable, switching to an alternative anchor drug may be considered.

Reference: ASHM – 2024 – Antiretroviral Guidelines; AMH – 2025 – Dolutegravir