Renal function in Japanese HIV-1-positive patients who switch to tenofovir alafenamide fumarate after long-term tenofovir disoproxil fumarate: a single-center observational study

Abstract

Background: Tenofovir disoproxil fumarate (TDF) has a strong antiviral effect, but TDF is known to cause renal dysfunction. Therefore, we are investigating preventing renal dysfunction by replacing TDF with tenofovir alafenamide fumarate (TAF), which is known to be relatively safe to the kidneys. However, the changes in renal function under long-term use of TAF are not known. In this study, we evaluated renal function in Japanese HIV-1-positive patients switching to TAF after long-term treatment with TDF.

Methods: A single-center observational study was conducted in Japanese HIV-1-positive patients. TDF was switched to TAF after at least 48 weeks of the treatment so we could evaluate the long-term use of TDF. The primary endpoint was the estimated glomerular filtration rate (eGFR) at 144 weeks of TAF administration. In addition, we predicted the factors that would lead to changes in eGFR after long-term use of TAF.

Results: Of the 125 HIV-1-positive patients who were prescribed TAF at our hospital during the study period, 70 fulfilled the study criteria. The eGFR at the time of switching from TDF to TAF was 81.4 ± 21.1 mL/min/1.73 m². eGFR improved significantly after 12 weeks of taking TAF but significantly decreased at 96 and 144 weeks. The factors significantly correlated with the decrease in eGFR at 144 weeks on TAF were eGFR and weight at the start of TAF.

Conclusions: In this study, it was confirmed that switching to TAF was effective for Japanese HIV-1-positive patients who had been taking TDF for a long period of time and had a reduced eGFR. It was also found that the transition status depended on the eGFR and weight at the time of switch. Since HIV-1-positive patients in Japan are expected to continue taking TAF for a long time, renal function and body weight should be carefully monitored.

Keywords: HIV; Renal function; Tenofovir alafenamide fumarate; Tenofovir disoproxil fumarate; eGFR.

Fig. 1

A Changes in eGFR (mean ± SE) of the patients taking TAF after taking TDF for more than 48 weeks. B Change in eGFR (mean ± SE) in patients taking TAF classified by eGFR values after taking TDF for more than 48 weeks. eGFR estimated glomerular filtration rate, TDF tenofovir disoproxil fumarate, TAF tenofovir alafenamide fumarate, TDF0 start of TDF, TAF0 start of TAF; TAF12, -24, -48, -96 and -144: 12 weeks, 24 weeks, 48 weeks, 96 weeks and 144 weeks after starting TAF. *p < 0.05 is defined as significant differences by the paired t-test

Fig. 2

A Changes in Uβ2MG (median ± interquartile range: IR) of the patients switching from TDF to TAF. B Changes in Uβ2MG (median ± interquartile range: IR) of the patients switching from TDF to TAF. TAF: tenofovir alafenamide fumarate; TAF0: start of TAF; TAF12, -24, -48, -96 and -144: 12 weeks, 24 weeks, 48 weeks, 96 weeks and 144 weeks after starting TAF. *p < 0.05 is defined as a significant difference by the Wilcoxon rank sum test between groups. ^†p < 0.05 is defined as a significant difference by Wilcoxon signed rank test for G1 group. ^‡p < 0.05 is defined as significant differences by the Wilcoxon signed rank test for the G2 group. ^§p < 0.05 is defined as significant differences by the Wilcoxon signed rank test for the G3a and G3b groups

Fig. 3

A Changes in BMI (mean ± SE) of the patients taking TAF after taking TDF for more than 48 weeks. B Changes in TG (mean ± SE) of the patients taking TAF after taking TDF for more than 48 weeks. TDF: tenofovir disoproxil fumarate; TAF: tenofovir alafenamide fumarate; TDF0: start of TDF; TAF0: start of TAF; TAF12, -24, -48, -96, and -144: 12 weeks, 24 weeks, 48 weeks, 96 weeks, and 144 weeks after starting TAF. *p < 0.05 is defined as a significant difference by the paired t-test