Diabetes mellitus affects more than 10% of people with HIV, and its incidence is rising as the population ages, according to the National Institutes of Health. Antiretroviral therapies that treat HIV by blocking specific enzymes the virus uses to multiply can cause metabolic complications, including weight gain and insulin resistance. Since 2015, integrase strand transfer inhibitor-based regimens have been recommended as first-line treatment. In a new Johns Hopkins Medicine study funded by the National Institutes of Health, researchers found adults with HIV who switched from protease inhibitors to integrase inhibitors were at increased risk of diabetes.
The study was published March 27 in The Lancet HIV.
"These findings help people with HIV make informed decisions when switching medications," says lead study author Yoseob Joseph Hwang, M.D., M.Sc. "Our analysis is not intended to discourage switching medications, but rather to inform patients and their treating clinicians of the potential metabolic risks that should be weighed in making individualized treatment decisions in such common clinical scenarios."
Hwang says the researchers emulated a target trial of 13,071 adults with HIV in the U.S. and Canada between 2016 and 2022. Participants without diabetes who had used non-nucleoside reverse transcriptase inhibitors or protease inhibitors for more than 180 days were followed from encounters in which they continued those medications or switched to an integrase strand transfer inhibitor for up to five years.
Researchers found a 38% higher risk of diabetes in people with HIV after switching from protease inhibitors to integrase strand transfer inhibitors. Hwang says this observation indicates that the medication change may have adverse metabolic impact, which may warrant close monitoring early after a switch, regardless of weight gain.
"Prior studies have looked at diabetes risk in new users of integrase strand transfer inhibitors," Hwang explained. "Our study specifically looked at people with HIV who switched to integrase strand transfer inhibitors, contributing to the growing body of evidence that implicates the medication with diabetes risk."
Hwang says the next steps in this research are to determine how integrase inhibitors affect people with preexisting diabetes.
Other researchers include Catherine R. Lesko, Ph.D., Todd T. Brown, M.D., G. Caleb Alexander, M.D., Keri N. Althoff, Ph.D., Lauren C. Zalla, Ph.D., Jarratt D. Pytell, M.D., Oluwaseun Falade-Nwulia, M.B.B.S., Eva Tseng, M.D., Richard D. Moore, M.D., Vincent C. Marconi, M.D., John R. Koethe, M.D., Michael J. Silverberg, Ph.D., Michael A. Horberg, M.D., Raynell Lang, M.D., Timothy R. Sterling, M.D., and Anthony Todd Fojo, M.D.
Brown has served as a consultant to ViiV Healthcare, Gilead Sciences, Janssen, and EMD Serono. Alexander is the past chair of the FDA's Peripheral and Central Nervous System Advisory Committee and a co-founding principal and equity holder in Stage Analytics. Alexander's arrangements have been reviewed and approved by The Johns Hopkins University in accordance with its conflict-of-interest policies. Althoff received grants from NIH, royalties from a Coursera specialization that she directs, and travel and lodging support for her role on the Scientific Steering Committee of the International Workshop on HIV and Hepatitis C virus Observational Databases. Pytell received grants from NIH. Falade-Nwulia received grants from NIH and AbbVie, consulting fees from Gilead Sciences, and served a leadership role in the International Network on Health and Hepatitis in Substance Users. Moore received grants from NIH. Marconi received grants from the U.S. Department of Veterans Affairs, the Centers for Disease Control and Prevention, NIH, Gilead Sciences, ViiV Healthcare, and Merck & Co; served on the advisory board for the following studies: IL-1b inhibitor study, OuTSMART, CLEAR HIV, ECLIPSE, and VB201; and served as a study section chair for NIH. Koethe served as an adviser to, and received grants from, Merck & Co. and Gilead Sciences. Horberg received grants from NIH. Sterling received grants from NIH. Other authors have no potential conflicts of interest to report.
This work was supported by National Institutes of Health grants U01AI069918, F31AI124794, F31DA037788, G12MD007583, K01AI093197, K01AI131895, K23EY013707, K24AI065298, K24AI118591, K24DA000432, KL2TR000421, N01CP01004, N02CP055504, N02CP91027, P30AI027757, P30AI027763, P30AI027767, P30AI036219, P30AI050409, P30AI050410, P30AI094189, P30AI110527, P30MH62246, R01AA016893, R01DA011602, R01DA012568, R01 AG053100, R24AI067039, U01AA013566, U01AA020790, U01AI038855, U01AI038858, U01AI068634, U01AI068636, U01AI069432, U01AI069434, U01DA03629, U01DA036935, U10EY008057, U10EY008052, U10EY008067, U01HL146192, U01HL146193, U01HL146194, U01HL146201, U01HL146202, U01HL146203, U01HL146204, U01HL146205, U01HL146208, U01HL146240, U01HL146241, U01HL146242, U01HL146245, U01HL146333, U24AA020794,U54MD007587, UL1RR024131, UL1TR000004, UL1TR000083, Z01CP010214 and Z01CP010176.
