Effects of antiretroviral combination therapies F/TAF, E/C/F/TAF and R/F/TAF on insulin resistance in healthy volunteers: The TAF-IR Study

Abstract

Background Increased insulin resistance (IR), associated with specific antiretroviral drugs or drug classes, is an established risk factor for type 2 diabetes in HIV patients, ultimately increasing morbidity and mortality. To date, data on the risk of IR in tenofovir alafenamide (TAF)-based protocols are unavailable. Methods This prospective randomized, open-label study evaluated the effects of IR on 30 healthy volunteers receiving fixed-dose combinations (FDCs) of emtricit-abine/tenofovir alafenamide (F/TAF), elvitegravir/cobi-cistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or rilpivirine/emtricitabine/tenofovir alafenamide (R/F/TAF). IR was measured before and after 14-day treatments using the hyperinsulinemic-euglycaemic clamp technique (HEGC). Changes in IR in each group were evaluated using the mean glucose disposal rate, normalized with body weight (MBW [mg glucose/(minxkg)]). Results A total of 30 subjects underwent randomization: one subject in the F/TAF arm withdrew consent after randomization and one in the R/F/TAF arm had to be excluded because of technical failure during HEGC, resulting in 28 subjects in the per-protocol population (F/TAF, n=9 subjects; E/C/F/TAF, n=10 subjects; R/F/TAF n=9 subjects). No significant differences were detected on the baseline characteristics. IR did not differ among the groups before treatment. None of the studied anti-retroviral combinations resulted in a significant change in IR after 14 days compared with baseline values, as measured by MBW (F/TAF, 11.42 ±3.04 mean [±sd] versus 11.43 ±3.23, P=0.49; E/C/F/TAF, 10.04 ±2.49 versus 10.95 ±4.26, P=0.30; R/F/TAF, 11.03 ±1.96 versus 13.01 ±4.11, P=0.13). Conclusions Short-term treatment for F/TAF, E/C/F/TAF or R/F/TAF did not increase IR in healthy male volunteers.

Editorial: Tenofovir disoproxil fumarate, more than an antiviral drug—Another piece of the puzzle

“…As a third effect, Chen and colleagues reported a subclinical but negative effect of switching from TDF to TAF on glucose homeostasis. However, this observation is in contrast with more sophisticated healthy volunteer studies which have not reported an effect of either TDF or TAF on insulin sensitivity 5,6 …”

“…However, this observation is in contrast with more sophisticated healthy volunteer studies which have not reported an effect of either TDF or TAF on insulin sensitivity. 5,6 In summary, TDF seems to have unique properties beyond its antiviral efficacy that result in a lowering of serum lipid concentrations and inhibiting weight gain. A beneficial effect on cardiovascular outcomes seems plausible, as reductions in weight and lipid levels are widely accepted as surrogate markers for a positive effect on cardiovascular events.…”

<p>The Effect of Switching from Tenofovir Disoproxil Fumarate (TDF) to Tenofovir Alafenamide (TAF) on Liver Enzymes, Glucose, and Lipid Profile</p>

“…Changes in BMI and Metabolic Variables from TDF-TAF short-term treatment of 14 days with EVG/COBI/FTC/ TAF 21. Nevertheless, our results could be justified by a longer exposure to EVG and TAF in our sample.…”

Glycemic Control in Patients Living With HIV Initiated on Integrase Inhibitor–Based Three-Drug Antiretroviral Therapy

“…In healthy men, short-term use of tenofovir alafenamide (TAF)/emtricitabine plus either rilpivirine or elvitegravir/ cobicistat did not increase insulin resistance. 7 Similarly, the use of tenofovir disoproxil fumarate (TDF)/emtricitabine plus either elvitegravir/cobicistat or darunavir/ritonavir did not increase insulin resistance in PLWH. However, there was a significant uptick in insulin resistance in those using TDF/emtricitabine plus lopinavir/ritonavir.…”