Does Antiretroviral Therapy for HIV Increase Risk of Incident Diabetes?
October 8, 2019

By Frances Morin

WASHINGTON, DC -- October 8, 2019 -- Integrase strand transfer inhibitor (INSTI)-based and protease inhibitor (PI)-based antiretroviral therapies (ART) for HIV are linked to an increased risk of incident diabetes compared with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapies, according to a study presented here at ID Week 2019, the Annual Meeting of the Infectious Diseases Society of America (IDSA).

INSTI-based ART is associated with more weight gain than other regimens, raising the question of whether the weight gain increases the risk of related comorbidities. However research is lacking on outcomes associated with overweight or obesity, including diabetes, said Peter F. Rebeiro, PhD, Vanderbilt School of Medicine, in Nashville, Tennessee.

For the current study, the researchers evaluated data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) from January 2007 to December 2016. They identified 21,516 eligible ART initiators, including 10,553 (49%) who started NNRTIs, 6,677 (31%) who started PIs, and 4,286 (20%) who started INSTIs. Patients were followed-up for a median of 3.0, 2.4, and 1.6 years, respectively.

Of those starting INSTI initiators, 21% received dolutegravir, 28% received raltegravir, and 51% received elvitegravir.

Patient follow-up included the period from ART initiation until the development of diabetes, virologic failure, regimen core switch, cohort close, death or loss to follow-up

Overall, 3% of the subjects (669) developed diabetes, defined as having either haemoglobin A1C >6.5%, diabetes-specific medication, or random glucose measure ≥200 mg/dL.

After adjusting for factors including age, sex, race, year of ART initiation, and baseline weight, results showed that patients initiating INSTIs had an increased risk of incident diabetes compared with those starting on NNRTIs (hazard ratio [HR] = 1.22; 95% confidence interval [CI], 0.95-1.57).

The adjusted risk of diabetes was also increased with PI-based treatment compared with NNRTI-based treatment (HR = 1.25; 95% CI, 1.05-1.49).

Initiating INSTIs with raltegravir, in particular, was associated with a 50% increased risk of diabetes compared with NNRTI initiation (HR = 1.50). The risk was lower with dolutegravir (HR = 1.14) and not increased with elvitegravir (HR = 0.96).

Limitations of the study included that exposure was not randomised, and the follow-up period for patients on INSTI-based treatment was shorter compared with other classes.

“Direct versus indirect effects of ART on incident diabetes [are needed] to determine if the elevated risk observed in these analyses are attributable partially to weight gain,” said Dr. Rebeiro.

ID Week is sponsored by the IDSA, the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), and the Pediatric Infectious Diseases Society (PIDS).

[Presentation title: The Effect of Initiating Integrase Inhibitor-Based vs Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy on Progression to Diabetes Among North American Persons in HIV Care. Abstract LB9]