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 emtricitabine/tenofovir alafenamide (F/TAF), elvitegravir/cobicistat/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/(min×kg)]).

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 antiretroviral 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.

• Authors: Christoph D Spinner, Sebastian Schulz, Ulrike Bauer, Jochen Schneider, Johanna Bobardt, Alexander Von Werder, Roland M Schmid, Alexander Zink, Eva Wolf, Roman Iakoubov
• Journal: Antiviral therapy (Antivir Ther) Vol. 23 Issue 7 Pg. 629-632 ( 2018) ISSN: 2040-2058 [Electronic] England
• PMID: 30281025 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Blood Glucose
• Drug Combinations
• Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• emtricitabine tenofovir alafenamide
• Tenofovir
• Rilpivirine
• Emtricitabine
• Adenine

Topics

• Adenine (analogs & derivatives)
• Adult
• Anti-HIV Agents (blood, pharmacokinetics)
• Blood Glucose (metabolism)
• Body Weight
• Drug Combinations
• Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination (blood, pharmacokinetics)
• Emtricitabine
• Glucose Clamp Technique
• Healthy Volunteers
• Humans
• Insulin Resistance (physiology)
• Male
• Prospective Studies
• Rilpivirine (blood, pharmacokinetics)
• Tenofovir