Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Feb 28;10(1):13.
doi: 10.1186/s40780-024-00336-y.

Renal function and lipid metabolism in Japanese HIV-1-positive individuals 288 weeks after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate: a single-center, retrospective cohort study

Kensuke Abe  1   2 , Junji Imamura  3 , Akiko Sasaki  3 , Tomoko Suzuki  3 , Satomi Kamio  4 , Taku Obara  5 , Toshihiro Ito  3
Affiliations

Renal function and lipid metabolism in Japanese HIV-1-positive individuals 288 weeks after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate: a single-center, retrospective cohort study

Kensuke Abe et al. J Pharm Health Care Sci. .

Abstract

Background: Continued use of tenofovir disoproxil fumarate (TDF), an antiretroviral drug, causes renal function decline and tubular damage in individuals with HIV. While tenofovir alafenamide fumarate (TAF) may have less damaging effects, it causes weight gain and abnormal lipid metabolism.

Methods: This single-center, retrospective cohort study used medical records from the National Hospital Organization Sendai Medical Center to investigate renal function of Japanese HIV-1-positive individuals who switched from TDF to antiretroviral therapy including TAF by 2017. The endpoints were: estimated glomerular filtration rate (eGFR), urinary β2 microglobulin (Uβ2MG), weight, and lipid metabolism parameters at 288 weeks after switching. Possible correlation between eGFR and Uβ2MG and factors affecting eGFR decline were examined.

Results: Sixty patients switched from TDF to TAF and continued therapy for 288 weeks. eGFR showed a significant decline after 144 weeks, although it was controlled from the time of change until 96 weeks. In the renal impairment group, the decline was suppressed until week 288. Uβ2MG continued to decrease significantly after 48 weeks. However, the suggested correlation between eGFR and Uβ2MG disappeared when patients switched from TDF to TAF. Weight and lipid metabolic parameters increased significantly at 48 weeks and were maintained. Factors associated with decreased eGFR were: history of acquired immune deficiency syndrome (AIDS) and Uβ2MG. However, considering the odds ratio, the switch from TDF to TAF suppressed the eGFR decline in the group with a history of AIDS, and Uβ2MG had no effect on the eGFR decline.

Conclusions: Switching from TDF to TAF for the long term slows eGFR decline, decreases Uβ2MG levels, and reduces worsening of renal function. Weight gain and abnormal lipid metabolism may occur in the short term but are controllable.

Keywords: HIV; Lipid metabolism; Renal function; Tenofovir alafenamide fumarate; Tenofovir disoproxil fumarate.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
A) Change in eGFR (mean ± SD) over 288 weeks in HIV-positive individuals who switched from TDF to antiretroviral therapy including TAF and continued taking it. B Change in eGFR (mean ± SD) over 288 weeks in each group classified by eGFR level at the time of switching from TDF to TAF (week 0, TAF0). In both (A) and (B), paired t-tested was performed at 48 weeks (TAF48), 96 weeks (TAF96), 144 weeks (TAF144), 192 weeks (TAF192), 240 weeks (TAF240), and 288 weeks (TAF288), using TAF0 as the reference, with a significance level of p < 0.05. The sample size of B) at each survey from TAF0 to TAF288 was 13 in group G1, 37 in group G2, and 10 in groups G3a, b. At TDF0, there were 8 in group G1, 32 in group G2, and 9 in groups G3a, b
Fig. 2
Fig. 2
A) Change in Uβ2MG (median; IQR) over 288 weeks in HIV-positive individuals who switched from TDF to antiretroviral therapy including TAF and continued taking it. B) Change in Uβ2MG (median; IQR) over 288 weeks in each group classified by eGFR level at the time of switching from TDF to TAF (week 0, TAF0). In both (A) and (B), Wilcoxon signed rank test was performed at 48 weeks (TAF48), 96 weeks (TAF96), 144 weeks (TAF144), 192 weeks (TAF192), 240 weeks (TAF240), and 288 weeks (TAF288), using TAF0 as the reference, with a significance level of p < 0.05. The sample size of B) at each survey from TAF0 to TAF288 was 11 in group G1, 33 in group G2, and 7 in groups G3a, b
Fig. 3
Fig. 3
Scatter plots of eGFR and Uβ2MG at (A) week 0 (TAF0) and (B) week 288 (TAF288) for 60 subjects
Fig. 4
Fig. 4
Changes in (A) BMI (mean ± SD), (B) TG (mean ± SD), (C) T-cho (mean ± SD), (D) HDL-cho (mean ± SD), and (E) LDL-cho (mean ± SD) over 288 weeks of individuals who switched from TDF to antiretroviral therapy including TAF and continued taking it. In A), B), C), D), and E), paired t-test was performed at 48 weeks (TAF48), 96 weeks (TAF96), 144 weeks (TAF144), 192 weeks (TAF192), 240 weeks (TAF240) and 288 weeks (TAF288), with TAF0 as the reference, and the significance level was set at p < 0.05
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Cihlar T, Chen M. Incorporation of selected nucleoside phosphonates and anti-human immunodeficiency virus nucleotide analogues into DNA by human DNA polymerases α, β and γ. Antivir Chem Chemother. 1997;8(3):187–195. doi: 10.1177/095632029700800302. - DOI
    1. Casado JL, Del Rey JM, Bañón S, et al. Changes in kidney function and in the rate of tubular dysfunction after tenofovir withdrawal or continuation in HIV-infected patients. J Acquir Immune Defic Syndr. 2016;72(4):416–422. doi: 10.1097/QAI.0000000000000986. - DOI - PubMed
    1. Ray AS, Cihlar T, Robinson KL, et al. Mechanism of active renal tubular efflux of tenofovir. Antimicrob Agents Chemother. 2006;50(10):3297–3304. doi: 10.1128/AAC.00251-06. - DOI - PMC - PubMed
    1. Hall AM, Hendry BM, Nitsch D, et al. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis. 2011;57(5):773–780. doi: 10.1053/j.ajkd.2011.01.022. - DOI - PubMed
    1. Babusis D, Phan TK, Lee WA, et al. Mechanism for effective lymphoid cell and tissue loading following oral administration of nucleotide prodrug GS-7340. Mol Pharm. 2013;10(2):459–466. doi: 10.1021/mp3002045. - DOI - PubMed