Journal Club

Integrase Strand Transfer Inhibitors and New-Onset Diabetes in People With HIV

By Krishna Rao, MD, MS

The specific recommendations for antiretroviral therapy (ART) for HIV infection have evolved over the years, but in 2022 integrase strand transfer inhibitors (INSTIs) constitute an important backbone of many regimens. While safer and better tolerated than past ART regimens, such as certain thymidine analogues and protease inhibitors, INSTIs have been associated with weight gain in several studies. However, there are limited data on whether INSTI-based regimens associate with other metabolic outcomes such as diabetes mellitus (DM) and hyperglycemia.

In this study in Clinical Infectious Diseases, O’Halloran and colleagues used the IBM MarketScan Commercial Database (2007-2019) and the Medicaid Multi-State Database (2011-2019) to assess the incidence of new-onset DM/hyperglycemia in the 6 months following INSTI-based ART initiation in patients with HIV. Given the retrospective, claims-based nature of the study and underlying data, the investigators used a propensity score for INSTI-based regimen initiation to perform a weighted Cox proportional hazards regression, and many potential confounders were captured such as demographics, geographic region, Medicaid status, and comorbidities. For assessing individual INSTIs, they re-performed the analysis including the four INSTI drugs in the same model versus non-INSTI-based regimens.

Of 42,382 patients that initiated ART, 54% were INSTI-based, 74% were male, and 19% were Medicaid-insured. Patients on INSTI-based regimens were 31% more likely to develop new-onset DM/hyperglycemia (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.15-1.48), with the highest risk from regimens containing elvitegravir (adjusted HR, 1.54; 95% CI, 1.32-1.97) and the lowest risk with raltegravir (adjusted HR, 1.19; 95% CI, 0.95-1.03). Additional analyses explored the following between treatment groups and found no notable differences/effects on the results: distribution of covariates, diabetes testing frequency, testing in the 2 weeks surrounding INSTI initiation (possible pre-existing DM), and use of tenofovir alafenamide (TAF) as part of ART. (TAF is independently associated with metabolic derangements.)

This large, retrospective, claims-based study identified initiation of INSTI-based ART for patients with HIV as an independent risk factor for new-onset DM/hyperglycemia in the first 6 months. While not the same as data from a randomized trial, this study was rigorously conducted and is in line with prior clinical literature suggesting INSTIs impact glycemic control. Thus, while awaiting further research to better characterize the risk, it would be wise for providers to remain vigilant regarding metabolic side effects after initiation of INSTI-based ART in their patients.

(O’Halloran et al. Clin Infect Dis. Published online: May 6, 2022.)