Integrase inhibitors did not increase diabetes risk among Italian men living with HIV

In a cohort of mostly middle-aged Italian men living with HIV, diabetes mellitus (DM) risk was not related to taking integrase inhibitors (INSTIs). Instead, risk factors for the metabolic disorder were primarily the same as those in the general population.

About This Study

“Incident diabetes in course of antiretroviral therapy” was published online on March 14, 2023, in AIDS. The lead author is Lucia Taramasso, M.D., Ph.D., of the Infectious Disease Clinic at IRCCS Policlinico San Martino Hospital in Genoa, Italy.

Key Research Findings

This study examined diabetes mellitus (DM) incidence in a prospective cohort of 4,366 PLWH from 2003-2021 to determine whether INSTIs increased DM risk. Seventy-three percent of participants were men, 91% were white, and the mean age was 46 years. At baseline, 2,627 participants were on an INSTI-based regimen, 1,288 were on a protease inhibitor-based regimen, and 451 were on a non-nucleoside reverse transcriptase inhibitor-based regimen.

One hundred twenty participants developed DM. The disease was correlated with higher baseline weight (but not weight gain), older age, untreated hypertension, and detectable HIV viral load at study start, but not with any particular ART regimen. This was true both for the anchor drug and when modeling individual ARVs–except for raltegravir, which was associated with an increased risk of diabetes compared to dolutegravir, a finding that was on the borderline of statistical significance.

Discussion Highlights and Implications for Practice

The authors pointed out that although baseline weight was associated with DM, weight gain—which was moderate among most participants—was not. This differs from studies conducted outside Europe, where weight increase was higher and related to developing DM.

Researchers described the limitations of the study, pointing out that the current observational cohort was not randomized to their ART regimen. Reasons for prescribing particular drugs may be related to DM risk, confounding the results. Data on physical activity, diet, and other factors was also not available.

The study authors also noted that the association between HIV viremia and diabetes seen in their study could be due to ongoing inflammation or to unmeasured confounders, such as behaviors that both increase weight and lead to poor ART adherence. They added that PLWH at risk of cardiovascular problems were often switched to raltegravir, the first integrase inhibitor available; thus, the higher DM risk seen among people on that drug vs. DTG may be related to factors other than the drug itself.

By Barbara Jungwirth