Risks of metabolic syndrome and diabetes with integrase inhibitor-based therapy

Curr Opin Infect Dis. 2021 Feb 1;34(1):16-24. doi: 10.1097/QCO.0000000000000695.

Abstract

Purpose of review: A growing body of evidence suggests that integrase inhibitors (INSTIs) are significantly associated with weight gain and obesity. Obesity is a significant risk factor for metabolic syndrome and diabetes. This article comprehensively reviews recent available evidence weight gain and the risks of metabolic syndrome and diabetes associated with INSTIs.

Recent findings: Recent evidence continues to contribute to the evidence for weight gain associated with INSTIs, especially when used with newer nucleoside reverse transcriptase inhibitor, tenofovir alafenamide (TAF). Although the literature suggests a neutral effect on lipids, there is evidence that INSTIs are associated with metabolic syndrome due to treatment-emergent obesity. The literature for short-term treatment-emergent diabetes and insulin resistance remains inconsistent, but there is some evidence that weight gain could lead to an increased risk of developing diabetes in the future.

Summary: Longer term studies are required to understand the metabolic impact of INSTIs, secondary to weight gain. Evidence suggests that INSTIs, when used with TAF, contribute to metabolic syndrome and may have long-term risks of diabetes. INSTIs, when used with tenofovir disoproxil fumarate, have fewer metabolic implications. Clinicians must monitor for weight gain and metabolic effects, especially in those with underlying risk factors.

Publication types

  • Review

MeSH terms

  • Alanine / adverse effects
  • Alanine / therapeutic use
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Diabetes Mellitus / etiology*
  • HIV Infections / drug therapy*
  • HIV Integrase Inhibitors / adverse effects*
  • HIV Integrase Inhibitors / therapeutic use
  • Humans
  • Metabolic Syndrome / etiology*
  • Tenofovir / adverse effects
  • Tenofovir / analogs & derivatives
  • Tenofovir / therapeutic use
  • Weight Gain / drug effects

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Tenofovir
  • tenofovir alafenamide
  • Alanine