Incidence of diabetes in HIV-infected patients treated with first-line integrase strand transfer inhibitors: a French multicentre retrospective study

Abstract

Background Integrase strand transfer inhibitors (INSTIs) are increasingly used in patients living with HIV due to their safety, effectiveness and high genetic barrier. However, an association with weight gain has recently been suggested and several cases of diabetes mellitus have been reported with raltegravir and dolutegravir. The long-time metabolic impact of these recent molecules remains unclear. Objectives To assess if an INSTI as a third agent is statistically associated with new-onset diabetes mellitus compared with an NNRTI or a PI. Patients and methods Patients undergoing first-line combined ART (cART) without diabetes at baseline were retrospectively included from the Dat’AIDS French cohort study (ClinicalTrials.gov NCT02898987). Incident diabetes mellitus was defined as a notification of new diabetes in the medical history, a glycated haemoglobin (HbA1c) level superior to 7.5% or the start of a diabetes therapy following the initiation of ART. Results From 2009 to 2017, 19 462 patients were included, among which 265 cases of diabetes mellitus occurred. Multivariate and survival analyses did not highlight an increase in new-onset diabetes in patients undergoing cART with an INSTI as a third agent compared with an NNRTI or a PI. BMI >30 kg/m2, age >37 years old (in survival analysis), black race or Hispanic ethnicity, arterial hypertension and AIDS were associated with a higher proportion of incident diabetes. Conclusions INSTIs were not statistically associated with new-onset diabetes. However, clinicians should remain aware of this possible metabolic comorbidity, particularly in patients with a high BMI and older patients.

Analysis of antiretroviral therapy switch rate and switching pattern for people living with HIV from a national database in Japan

“…Of note, recent literatures have informed clinicians to remain aware of possible metabolic comorbidity despite inconclusive findings in the literature. Rebeiro et al 28 , reported that initiating first cART regimens with INSTIs or PIs vs NNRTIs may confer greater risk of diabetes mellitus, likely mediated through weight gain, while Ursenbach et al 29 , reported that INSTIs were not statistically associated with new-onset diabetes. The potential issue of metabolic comorbidity is not investigated in our current study; however, it is an important topic that warrant further investigation.…”

Liver Fat, Adipose Tissue, and Body Composition Changes After Switching from a Protease Inhibitor or Efavirenz to Raltegravir

“…Because of our short follow-up time, we cannot evaluate long-term duration of the presumed improvement in adipose tissue function. However, data from large cohort studies might imply this, since RAL was not associated with increased risk of diabetes mellitus 38 or cardiovascular events 39 despite increased weight gain, 40 although a very recent study showed an increased risk of diabetes mellitus with RAL. 41 The main strength and novelty of our study is the comprehensive approach to interrelate findings on body composition, liver fat, and adipose tissue with metabolic and inflammatory variables.…”

Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment

“…Multivariate and survival analyses did not highlight an increase in new-onset diabetes in patients undergoing combination ART with an INSTI as a third agent (relative to an NNRTI or a PI). BMI, age, African or Hispanic ethnicity, arterial hypertension, and AIDS were associated with a higher incidence of diabetes (197).…”