In Japanese HIV-1-positive patients, a long time after switching from TDF to TAF, Uβ2MG significantly improved, but eGFR showed a significant decrease at 144 weeks. BMI increased moderately within the normal range. TG reached its highest value at 48 weeks but did not show a significant difference from the TDF0 or TAF0 value at 144 weeks.
Patients in this study had a significant decrease in eGFR from the time they started taking TDF to the time they switched to TAF. In order to improve or prevent the decline in eGFR, all patients who were taking TDF were switched to TAF. At 12 weeks after switching, eGFR significantly increased from the time of switching and then gradually decreased, and eGFR at 96 and 144 weeks was significantly lower than that at the start of TAF. Therefore, even though TAF is considered to be better for renal function than TDF, the eGFR of Japanese HIV-1-positive patients was significantly decreased after switching from long-term TDF to long-term TAF.
In order to confirm the trend of eGFR in detail, the patients were divided into 3 groups, according to a published eGFR classification , based on their eGFR value at the time of switching to TAF. In the G1 group, with high eGFR, eGFR continued to decrease after switching from TDF to TAF and had significantly decreased by 24 weeks. In the G2 group, with moderate eGFR, there was a temporary recovery of eGFR. In the G3a and G3b groups, with low eGFR, eGFR started increasing significantly 12 weeks after switching to TAF, and there was no significant decline from baseline by 144 weeks. Yoshino et al. reported the recovery of 3 groups of Japanese HIV-positive patients who had decreased eGFR due to taking TDF and discontinued TDF. Among them, the median value of eGFR at the time of the switch was higher in the group that showed a worsening of eGFR even after discontinuation of TDF than in the recovery group and the mild recovery group . These findings are consistent with our present progress report. Furthermore, according to Pozniak et al., when eGFRCG was divided into < 50 mL/min and ≥ 50 mL/min groups and progression was observed at 24 and 48 weeks, eGFRCG increased from baseline in the < 50 mL/min group at both 24 and 48 weeks but decreased in the ≥ 50 mL/min group. The eGFRCG was elevated from baseline in the < 50 mL/min group at 24 and 48 weeks but decreased in the ≥ 50 mL/min group . TDF is known to cause tubular damage, and Uβ2MG is recommended as a test marker for tubular damage . In our study, as shown in Fig. 2-A, there was a significant decrease 12 weeks after switching from TDF to TAF, and the decrease continued thereafter, suggesting that tubular damage was improved. In addition, we investigated the course of Uβ2MG by GFR class, as shown in Fig. 2-B. We found that Uβ2MG was higher only in the G3a and G3b groups, in which it was significantly higher than that in the G1 and G2 groups. After switching from TDF to TAF, Uβ2MG continued to decrease significantly in the G3a and G3b groups.
In summary, we believe that switching from TDF to TAF is effective in preventing the decline in eGFR and tubular damage in the low-eGFR group (eGFR less than 60 mL/min/1.73 m2). However, in the group with an eGFR of 60 mL/min/1.73 m2 or higher, the eGFR was significantly reduced by continuing to take TAF for a long period of time, though the extent of the decrease was not clear from the data in this study. We think it will be important to confirm the situation at 192 weeks and 240 weeks in the future.
In recent years, there have been many reports of weight gain and abnormal lipid metabolism associated with taking TAF [24, 25, 26]. In a report by Kuo PH et al. in Taiwanese HIV-positive individuals, another Asian ethnicity, significant weight gain and an increase in TG were observed at 48 weeks after switching from non-integrase inhibitor-based antiretroviral therapy to coformulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide . Therefore, in this study, we fixed the third agent class drugs and confirmed the changes in BMI and TG after switching from TDF to TAF. BMI showed a significant increase 12 weeks after switching from TDF to TAF but was within the normal range for Japanese people. TG was highest at TAF48 but declined thereafter and was not significantly different from baseline at TAF96 or TAF144. We believe that the reason for these findings is that information on weight gain and abnormalities in lipid metabolism caused by several anti-HIV drugs has been given to patients, and guidance on diet has been implemented during patient visits. Therefore, we consider that it is possible to prevent weight gain and abnormalities in lipid metabolism through an appropriate diet, even if the patient is taking TAF, but this is difficult to track and control in real-world settings.
To predict the factors associated with the change in eGFR after taking TAF, we performed a multiple regression analysis using the variables shown in Table 2, with the difference in eGFR from TAF0 to TAF144 as the objective variable. We predicted the factors associated with the objective variable based on the values of each item at 48 weeks, which we considered the best time to evaluate the effects of TAF because the changes in eGFR between GFR classes  differed at this time, as shown in Fig. 1-B. Turner D et al. reported that they did not find any factors associated with changes in eGFR from before to after switching from TDF to TAF . However, in our long-term follow-up after switching from TDF to TAF, age (p = 0.039) and ΔeGFR (p < 0.0001) were significantly associated with the objective variable. On the other hand, Kawamoto R et al.  and Nomura I et al.  reported that increased BMI is associated with decreased eGFR in Japanese patients. However, we did not find any association in this study. The reason for this is that although BMI increased significantly from TAF0 to TAF144 in our patients, it remained within the normal range for Japanese people. The eGFR decrease was suppressed by switching to TAF, and eGFR ≥ 50 mL/min/1.73 m2 was maintained. It should be noted that the results of this study differ from the results of previous studies but may be related, as long-term use of TAF may increase BMI and decrease eGFR.
This study was conducted at a single institution with a small sample size of only Japanese subjects, which are the main limitations of the study. However, this study design is a result of strict regulations and the elimination of missing survey items. We are the first to present the actual eGFR values of Japanese HIV-1-positive patients taking TDF for longer than 48 weeks and then continuing to take TAF for 144 weeks. We also detailed the course of eGFR trends up to 144 weeks after switching from TDF to TAF and predicted the factors affecting the difference from baseline after 144 weeks of taking TAF. This study also provides new details on other renal functions, such as the status of tubular damage as indicated by Uβ2MG, after the transition from baseline to 144 weeks of taking TAF. Furthermore, since there are few reports on BMI and TG after long-term use of TAF in Japanese individuals, these factors were also investigated.
Switching from TDF to TAF may temporarily improve renal function, but long-term use of TAF may lead to a decline in renal function, so continuous monitoring of renal function from all aspects is necessary.