TAF vs TDF: How Much of a Difference?

W. David Hardy, MD

Immediate Past-Chair, Board of Directors, HIVMA

Adjunct Professor of Medicine

Craig W. Hendrix, MD (Pinch-hitting)

Professor of Medicine, Pharmacology, and Epidemiology

Johns Hopkins University School of Medicine

Do All Patients Need TAF?

F/TAF F/TDF Difference

N = 2694 N = 2693

Global Categories % % absolute %

Treatment-Emergent Adverse Event 92.7 92.6 0.1

Treatment-Emergent Study Drug-Related Adverse Event 20.2 23.4 -3.2

Grade 2, 3, or 4 Treatment-Emergent Study Drug-Related Adverse Event 3.2 4.1 -0.9

Grade 3 or 4 Treatment-Emergent Study Drug-Related Adverse Event 0.3 0.5 -0.2

Treatment-Emergent Study Drug-Related Serious Adverse Event 0.1 0.2 -0.1

Treatment-Emergent Adverse Event Leading to Premature Study Drug Discontinuation 1.3 1.8 -0.5

Treatment-Emergent Death 0.1 0.1 0.0

Symptoms

Diarrhea 5 5.9 -0.9

Nausea 4.2 4.6 -0.4

Headache 2.2 2.1 0.1

Fatigue 1.6 2.7 -1.1

Abdominal pain 1 1.3 -0.3

Flatulence 0.8 1.2 -0.4

Abdominal discomfort 0.7 1.1 -0.4

Laboratory (Gr 3/4 in >1% of ppts)

Increased alanine aminotransferase 1.5 1.5 0.0

Increased amylase 1.3 1.7 -0.4

Increased aspartate aminotransferase 2.4 1.9 0.5

Hyperglycemia (nonfasting) 0.6 1.2 -0.6

Increased low-density lipoprotein (fasting) 2.2 0.8 1.4

Glycosuria 0.7 1.2 -0.5

PrEP Adverse Events: Discover

Source: Gilead & FDA Briefing Document FDA Advisory Committee

PrEP Adverse Events: Discover

Source: Gilead & FDA Briefing Document FDA Advisory Committee

Renal Week

F/TAF

% change

F/TDF

% change

Absolute

% DIFF p value

Serum Creatinine (mg/dL) 48 -1.1 1.1 -2.1 < 0.001

96 1.1 2.1 -1.1 < 0.001

eGFRCG (mL/min) 48 1.5 -1.9 3.3 < 0.001

96 -0.5 -3.4 2.9 < 0.001

Urine beta-2-microglobulin to Urine Creatinine ratio (μg/g) 48 -10.7 15.3 -26.0 < 0.001

96 -17.2 11 -28.2 < 0.001

Urine RBP to Urine Creatinine ratio (μg/g) 48 0.2 19.9 -19.7 < 0.001

96 -2.1 19.9 -22.0 < 0.001

% UPCR >200 mg/g 48 0.7 1.5 -0.8 = 0.005

96 1.3 1.2 0.1 NS

% Proteinuria Urine Dipstick 21.3 24.3 -3.0 = 0.009

Bone (N=158)

Hip Bone Mineral Density 48 0.2 −1.0 -1.1 < 0.001

Spine Bone Mineral Density 48 0.5 −1.1 -1.6 < 0.001

Lipids

Fasting Total Cholesterol 48 -0.6 -6.4 5.8 <0.05

96 -2.3 -8.1 5.8 <0.05

Fasting HDL 48 -4.1 -10.0 5.9 <0.05

96 -2.0 -8.0 6.0 <0.05

Fasting LDL 48 1.0 -6.5 7.5 <0.05

96 -4.0 -8.0 4.0 <0.05

Fasting Total Chol/HDL Ratio 48 3.1 3.3 -0.2 NS

96 0.8 -0.4 1.2 NS

Fasting Triglycerides 48 4.3 0.0 4.3 <0.05

96 2.2 -5.4 7.5 <0.05

Renal function trajectories after switching from TDF to TAF

A nationwide cohort study

Bernard Surial, Bruno Ledergerber, Alexandra Calmy, Matthias Cavassini, Huldrych Günthard, Helen Kovari,

Marcel Stöckle, Enos Bernasconi, Pietro Vernazza, Christoph Fux, Hansjakob Furrer, Andri Rauch, Gilles Wandeler,

and the Swiss HIV Cohort Study (SHCS)

@b_surial

Share your thoughts on this presentation with #IAS2019

Change in eGFR over time

Adjusted for age, sex, ethnicity, diabetes, arterial hypertension, cardiovascular disease, HCV and HBV infection,

use of ritonavir, cobicistat, dolutegravir and cotrimoxazole

Change in eGFR over time

Adjusted for age, sex, ethnicity, diabetes, arterial hypertension, cardiovascular disease, HCV and HBV infection,

use of ritonavir, cobicistat, dolutegravir and cotrimoxazole

Change in eGFR over time

Adjusted for age, sex, ethnicity, diabetes, arterial hypertension, cardiovascular disease, HCV and HBV infection,

use of ritonavir, cobicistat, dolutegravir and cotrimoxazole

Adverse Event Profile Summary

• Differentiate statistically significant from clinically Significant

• All of the important event frequencies are very small

• Nearly all of the F/TAF vs. F/TDF differences are even smaller

• Boosted F/TAF more consistent advantages than F/TDF

• Clinicians & patients need to consider occasional clinical situations where F/TAF or F/TDF are favored

Truvada safety lawsuits

ANDREA WEDDLE, HIV MEDICINE ASSOCIATION

The chairs of the HIV Medicine Association and the American

Academy of HIV Medicine - August 7, 2019 By W. David Hardy

and Margaret L. Hoffman-Terry

www.poz.com

https://www.positivelyaware.com/articles/truvada-safety

Clinician & Public Health Responses

• Medical care dictated by lawyers not healthcare providers

• Need for PLWH and those at higher risk to consult with their healthcare providers

• Individualize treatment and prevention

• Undermining public health

• Unnecessary and destructive harm due to unsupported fear of toxicity