Data suggest limited change to diabetes risk following switch to integrase inhibitors

While there may be a short-term increase in diabetes risk among people living with HIV who switched treatment from protease inhibitors or non-nucleoside reverse transcriptase inhibitors to integrase inhibitors, that risk was attenuated in the long term, a recently published U.S. study found.

About This Study

“Association between switching to integrase strand transfer inhibitors and incident diabetes in people with HIV: a longitudinal cohort study” was published online on June 12, 2024, in AIDS. The lead author is Y. Joseph Hwang, M.D., M.Sc., of the Department of Medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland.

Key Research Findings

This observational cohort study at a single U.S. clinic assessed the risk of developing diabetes in 2,075 people living with HIV who either switched to an integrase inhibitor-based treatment regimen upon visiting the clinic (n=631) or remained on a protease inhibitor- or non-nucleoside reverse transcriptase inhibitor-based regimen after the visit (n=22,116). In both groups, the median was age over 50 years, about two-thirds of participants were assigned male at birth, and around three-quarters of participants were Black.

Participants who switched to an integrase inhibitor were more likely to have chronic liver disease (26% of that group vs. 20% of the remaining group), dyslipidemia (33% vs. 19%, respectively, of the two groups) and/or hypertension (44% vs. 32% of the two groups). While the median body mass index at the switch or comparator visit was similar between the groups (around 26 kg/m²), 64% of participants who stayed on their regimen continued to take tenofovir disoproxil fumarate, known to suppress weight, compared to 44% of participants who switched to an integrase inhibitor. The reverse was true for tenofovir alafenamide, an alternative to disoproxil fumarate without effect on weight: 2% of participants who did not switch to an integrase inhibitor started that drug compared to 22% of switch participants.

Although the risk of incident diabetes was initially higher in the switch group (weighted hazard ratio of 1.79), that difference disappeared after two years, with no difference over 10 years. That association remained even if no weight was gained during the first two years after switching.

Discussion Highlights and Implications for Practice

Study limitations reported included potential residual confounding about the reasons for switching, reliance on prescription records to determine medication exposure, and the single-site nature of the study.

These study authors observed that there was no long-term diabetes risk when HIV treatment was changed to an integrase inhibitor.

Recent reports on TheBodyPro support this thinking. While some studies have found an increased risk of weight gain within two years of switching to an integrase inhibitor, recent research suggests that the observed changes do not hold for the entire drug class and may be related to concurrent switching between the two tenofovir versions.

By Barbara Jungwirth