Safety Outcomes / Diabetes

5E-02 - Risk of Diabetes in People Living with HIV Associated with Remaining on a TDF-containing Antiretroviral Regimen or Switching to a TAF-containing Regimen or Another Regimen Without Tenofovir

Tuesday, August 26, 2025

8:45 AM - 9:00 AM ET

Presenting Author(s)

RK

Randall L. Kuffel, ScM

Student
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, United States

Co-Author(s)

LE

Lianeris M. Estremera-Rodriguez, MS, JD

Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
Baltimore, Maryland, United States
Y. Joseph Hwang, MD, MSc

Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
Baltimore, Maryland, United States
JH

Jason Haw

Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, United States
JK

Jeanne Keruly

Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America, United States
LZ

Lauren Zalla

Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, United States
LS

LaQuita Snow

Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America, United States
JJ

Joyce Jones, MD, MS

Assistant Professor
Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America, United States
RM

Richard D. Moore, MD

Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America, United States
AF

Anthony Fojo

Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America, United States
CL

Catherine Lesko, PhD, MPH

Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, Connecticut, United States

Background: Tenofovir-containing antiretroviral therapy (ART) regimens have become the first-line treatment for most people with HIV (PWH). Although the newer formulation tenofovir alafenamide (TAF) has a more favorable renal and bone safety profile, it also has metabolic concerns when compared to the older formulation tenofovir disoproxil fumarate (TDF). Switching from TDF to TAF is associated with weight gain, which is a major risk factor for developing type 2 diabetes in adults.

Objectives: Estimate the effect of switching from a TDF-containing ART regimen to either a TAF-containing ART regimen or an ART regimen without tenofovir on the risk of incident diabetes.

Methods: We emulated a three-arm trial in a cohort of PWH receiving comprehensive HIV care in the Johns Hopkins HIV Clinical Cohort (Baltimore, Maryland, USA) from November 2015 (TAF market entry) through September 2023. PWH ≥18 years without history of diabetes who had used a TDF regimen for ≥180 days and evidence of HIV viral suppression were eligible for the study. We followed participants from first eligible clinic visit until first occurrence of diabetes, death, loss to follow-up (>365 days without a follow-up visit), or end-of-study (September 2023). Each participant could contribute multiple eligible visits. Our exposure classified each eligible visit according to whether participants 1) switched from a TDF-containing regimen to a TAF-containing regimen, 2) switched to a regimen without tenofovir, or 3) continued a TDF-containing regimen (reference group). Our primary outcome was incident diabetes, defined as first occurrence of (i) HbA1c ≥6.5%, (ii) initiation of diabetes-specific medication, or (iii) new diabetes diagnosis and initiation of diabetes-related medication. We estimated the relative hazard of diabetes using an inverse probability treatment weighted Cox regression, controlling for confounding and between-group differences in baseline demographics, BMI categories, comorbidities, and co-prescriptions.

Results: We identified 758 patients (mean age 49 years, 62% male, 74% Black) who contributed 2247 observations (continued TDF=1753, switched to TAF=433, switched to a regimen without tenofovir=61). Over a median follow-up of 3.9 years, there were 349 diabetes events. Switching from TDF to TAF was not associated with a significantly higher hazard of diabetes (HR 1.08, 95% CI [0.82-1.42]), but switching to a regimen without tenofovir was (HR 2.5, 95% CI [1.44-4.31]).

Conclusions: Switching from a TDF-containing regimen to a regimen without tenofovir was associated with a significantly higher risk of diabetes in this cohort of PWH receiving comprehensive care. Future studies may elucidate the effect of switching to TAF from TDF in a larger, more diverse cohort of PWH.