Outcomes Associated With Treatment Change From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-1-Infected Patients

A Real-World Study in Japan

Naoki Kanda; Koh Okamoto; Hisatoshi Okumura; Makiko Mieno; Kentaro Sakashita; Teppei Sasahara; Shuji Hatakeyama


HIV Medicine. 2021;22(6):457-466. 

In This Article

Abstract and Introduction


Objectives: To investigate the impact of switching from tenofovir disoproxil fumarate (TDF)- to tenofovir alafenamide (TAF)-containing regimens on bone, kidney, serum lipids and body weight among Asian patients.

Methods: A prospective, multicentre, observational cohort study was conducted at three centres for HIV infection in Japan during 2017–2019. HIV-infected adults previously treated with TDF-containing regimens and scheduled to switch to TAF-containing regimens were included. Bone mineral density (BMD), renal markers, lipids and weight were measured consecutively from 12 months before to 12 months after the switch.

Results: Among 118 patients evaluated, the mean percentage change to spine BMD during 1 year of TAF treatment was higher than that during 1 year of TDF treatment (mean difference = 1.9%; 95% confidence interval (CI): 0.8–3.1). Urine protein and β2-microglobulin levels decreased significantly after the switch, while low-density lipoprotein cholesterol and triglycerides increased. During the TDF and TAF periods, the mean weight gains were 0.2 and 1.9 kg, respectively (mean difference = 1.6 kg; 95% CI: 0.9–2.3). Subgroup analysis revealed a significant difference between the mean body weight change associated with an integrase inhibitor (INSTI) (+2.8 kg) and that associated with a non-INSTI (+1.2 kg) third agent treatment only during the TAF period.

Conclusions: Among predominantly Japanese HIV-infected patients, BMD and renal tubular markers improved, while lipid profiles worsened significantly after the switch. Weight gain during the TAF period was larger than that during the TDF period. Concurrent use of INSTI with TAF may act synergistically to gain body weight.


Tenofovir disoproxil fumarate (TDF) is a long-standing cornerstone of antiretroviral therapy (ART) for HIV infection and remains one of the first-line agents recommended by international guidelines.[1] However, renal toxicity, including Fanconi syndrome, and bone toxicity [i.e. decreased bone mineral density (BMD)] are known side-effects of TDF and a major concern in the life-long treatment of patients with HIV infection.[2]

Tenofovir alafenamide (TAF), another prodrug of tenofovir, is metabolized differently in the human body; compared with TDF, it maintains higher tenofovir intracellular levels despite lower tenofovir plasma levels.[3] Because of this pharmacokinetic feature, the safety profile of TAF is expected to be superior to that of TDF. TAF, in combination with different antiretroviral agents, has been associated with satisfactory efficacy and lower risk of renal and bone toxicities compared with TDF in treatment-naïve and treatment-experienced HIV-infected patients in randomized controlled trials[4–8] and cohort studies.[9,10] Consequently, TAF has been included among the first-line backbone agents recommended by international guidelines.[1]

However, patients included in these large trials were predominantly of Caucasian and African-American origin. Patients of Asian origin accounted for approximately 5–6% of the study population.[11] Considering such under-representation, data regarding the effectiveness of switching from TDF to TAF on reducing renal and bone toxicities in Asian patients with HIV infections remain scarce.[12] Further studies are needed to adequately inform HIV treatment in Asian populations.

Weight gain following initiation of ART has recently gained attention. Weight gain associated with ART has been shown to increase the risk of diabetes and cardiovascular diseases.[13] A pooled analysis of randomized comparative clinical trials has found the ART regimens' composition to affect weight gain.[14] Specifically, patients following TAF-containing regimens gained c. 3 kg in 1 year; TAF was associated with the largest weight gain compared with TDF, abacavir and zidovudine among nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). Similarly, a few studies have reported on weight gain after switching from TDF- to TAF-containing regimens;[15,16] however, data representative of Asian populations are limited.

In Japan, the TAF-containing fixed-dose combination tablets of TAF/emtricitabine/elvitegravir/cobicistat and TAF/emtricitabine were approved in 2016 and 2017, respectively. Since then, medical practice steadily switched from TDF- to TAF-containing regimens in eligible patients. This study evaluated the impact of switching from TDF- to TAF-containing regimens on BMD, renal tubular biomarkers and body weight in Japanese patients with HIV-1 infection.