Risk of Incident Diabetes Mellitus, Weight Gain, and Their Relationships With Integrase Inhibitor-Based Initial Antiretroviral Therapy Among Persons With Human Immunodeficiency Virus in the United States and Canada.

Abstract

BACKGROUND:

Integrase strand transfer inhibitor (INSTI)-based combination antiretroviral therapy (cART) is associated with greater weight gain among persons with human immunodeficiency virus (HIV), though metabolic consequences, such as diabetes mellitus (DM), are unclear. We examined the impact of initial cART regimen and weight on incident DM in a large North American HIV cohort (NA-ACCORD).

METHODS:

cART-naive adults (≥18 years) initiating INSTI-, protease inhibitor (PI)-, or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from January 2007 through December 2017 who had weight measured 12 (±6) months after treatment initiation contributed time until clinical DM, virologic failure, cART regimen switch, administrative close, death, or loss to follow-up. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DM by cART class. Mediation analyses, with 12-month weight as mediator, similarly adjusted for all covariates.

RESULTS:

Among 22 884 eligible individuals, 47% started NNRTI-, 30% PI-, and 23% INSTI-based cART with median follow-up of 3.0, 2.3, and 1.6 years, respectively. Overall, 722 (3%) developed DM. Persons starting INSTIs vs NNRTIs had incident DM risk (HR, 1.17 [95% CI, .92-1.48]), similar to PI vs NNRTI initiators (HR, 1.27 [95% CI, 1.07-1.51]). This effect was most pronounced for raltegravir (HR, 1.42 [95% CI, 1.06-1.91]) vs NNRTI initiators. The INSTI-DM association was attenuated (HR, 1.03 [95% CI, .71-1.49] vs NNRTIs) when accounting for 12-month weight.

CONCLUSIONS:

Initiating first cART regimens with INSTIs or PIs vs NNRTIs may confer greater risk of DM, likely mediated through weight gain.

• Authors: Peter F Rebeiro, Cathy A Jenkins, Aihua Bian, Jordan E Lake, Kassem Bourgi, Richard D Moore, Michael A Horberg, W Christopher Matthews, Michael J Silverberg, Jennifer Thorne, Angel M Mayor, Viviane D Lima, Frank J Palella, Michael S Saag, Keri N Althoff, M John Gill, Cherise Wong, Marina B Klein, Heidi M Crane, Vincent C Marconi, Bryan E Shepherd, Timothy R Sterling, John R Koethe
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 73 Issue 7 Pg. e2234-e2242 (10 05 2021) ISSN: 1537-6591 [Electronic] United States
• PMID: 32936919 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Anti-HIV Agents
• HIV Integrase Inhibitors
• Reverse Transcriptase Inhibitors

Topics

• Adult
• Anti-HIV Agents (therapeutic use)
• Canada
• Diabetes Mellitus (drug therapy, epidemiology)
• HIV
• HIV Infections (drug therapy, epidemiology)
• HIV Integrase Inhibitors (therapeutic use)
• Humans
• Reverse Transcriptase Inhibitors (adverse effects)
• United States (epidemiology)
• Viral Load
• Weight Gain