Late Breaking Abstract Submission
Joseph J. Eron, Jr., MD
Professor of Medicine
University of North Carolina
Chapel Hill, NC
Disclosure: Gilead Sciences: Consultant, Research Grant, The research grants/contract are to the University of North Carolina on which i am an investigator.
Janssen: Consultant, Research Grant, The research grants/contract are to the University of North Carolina on which i am an investigator.
Merck and Co.: Consultant
ViiV HealthCare Inc: Consultant, Research Grant, The research grants/contract are to the University of North Carolina on which i am an investigator.
Background: Integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) has been implicated in greater weight gain than other regimens among people with HIV, but there is little evidence about its role in serious clinical outcomes proximal to weight gain. We therefore examined the impact of initial ART regimen class/drug on incident diabetes mellitus (DM) in a large North American HIV cohort.
Methods: Treatment-naïve adults (≥18 years) initiating INSTI-, protease inhibitor (PI)-, or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART from 01/2007 to 12/2016 in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were included. Individuals were followed until date of incident DM (HgA1c >6.5%, diabetes-specific medication, DM diagnosis along with diabetes-related medication, or random glucose measure ≥200 mg/dL), virologic failure, regimen core switch, cohort close (through 12/2016), death date, or loss to follow-up (≥12 months with no contact before cohort close). Cox regression stratified by site and adjusting for age, sex, race, HIV transmission risk, year of ART initiation, and baseline weight, CD4+ cell count, and HIV-1 RNA yielded adjusted hazard ratios (HR) and 95% confidence intervals (CI) for incident DM by ART class and INSTI drug.
Results: Among 21,516 eligible ART initiators, 10,553 (49%) started NNRTIs, 6,677 (31%) PIs, and 4,286 (20%) INSTIs, with median follow-up of 3.0, 2.4, and 1.6 years, respectively. Among INSTI initiators, 21% started dolutegravir (DTG), 28% raltegravir (RAL), and 51% elvitegravir (EVG). Overall, 669 (3%) developed DM. Patients differed by all characteristics except baseline body mass index and HIV-1 RNA. Those starting INSTIs vs NNRTIs had increased risk of incident DM (HR=1.22; CI: 0.95-1.57) similar in magnitude as for PI- vs. NNRTI-initiators (HR=1.25; CI: 1.05-1.49) (Figure). Among INSTIs, starting RAL- vs. NNRTI-based ART was associated with a 50% increased risk of DM (HR=1.50, CI: 1.11-2.03).
Conclusion: Initiating ART with INSTI- or PI- vs. NNRTI-based regimens may confer increased risk of incident DM, though risk is heterogeneous among INSTIs. Further research is needed to determine if this elevated risk can be attributed to weight gain.