In this study, we reported the changes in biomarkers of renal function and bone metabolism, and lipid profile when switching from TDF to TAF in HIV-infected patients. During the study, all the patients continued the TAF-containing regimen of ARVs that showed potent viral suppression. There were no serious adverse effects in the first 6 months after switching to TAF-containing regimen.
There were no noticeable changes in the eGFR calculated using creatinine levels, and cystatin-C levels during the study period. The L-FABP levels and the rate of proteinuria were significantly decreased. These results might be subclinical for majority of the participants without having CKD. However, it has been reported that the renal function in Japanese HIV-infected patients decreased depending on the duration of treatment with TDF, especially in patients with low body weight (14). Another observational study of a 12-year period also showed that decreased eGFR occurred after 3 months of TDF-containing regimen of ARVs, which was also related to low body weight (15).
Because L-FABP was reported as a potential marker of CKD for patients without albuminuria(16), the detection of subclinical changes using urinary L-FABP prior to the progression to CKD is important in patients taking TAF, especially in those with low body weight.
The elevation of biomarkers of lipids such as LDL-C was observed to have significance. Previous studies have also shown the elevation in the LDL-C and TG levels, but the range of elevation depended on the observational period, and the characteristics of the participants (17–19). One of the major risks for hyperlipidemia that was identified after switching to TAF was the elevation at beginning in TG or LDL-C levels (20) although opposite results also reported (21). In our study, LDL-C levels increased regardless of the hyperlipidemia at baseline. This risk population, that needs lipid-lowering drugs after switching TAF from TDF, must be extensively studied in the future.
Among the biomarkers of bone metabolism, U-NTx significantly decreased in our study. Previous study showed TDF-sparing regimen decreased the level of biomarkers of bone metabolism such as osteocalcin and bone alkaline phosphatase (13), and switching from TDF to TAF also improved bone mineral density (22). Although it is unclear whether tenofovir directly influences osteoblasts, a change in gene expression was observed with tenofovir exposure in vitro (23). Because U-NTx levels related bone mineral density levels in older men and women(24), U-NTx could also be used to predict current osteoporosis in TDF-exposure patients.
Here, the renal function and bone metabolism had improved within 6 months after switching to TAF. However, attention must be drawn to whether the lipid metabolism could be elevated up to the level that needs statin treatment.
According to patients’ genetic background (25, 26) the presence of various comorbidities, and body weight (14), clinicians might be required to determine whether to continue TDF or switch to TAF to prevent the progression to renal tubular dysfunction or metabolic disorders, using biomarkers such as urinary L-FABP and NTx. Its tailor-made design would help lives without disabilities of HIV-infected patients on ARVs.
Nevertheless, there were some limitations to our study. First, the information on the changes in lifestyle, such as new exercise habits and dietary patterns, were not collected using a questionnaire, although the treating physicians had recorded the changes in lifestyle and adherence to ARVs during each visit and no other drugs was changed. Second, the study did not have long observational period. Finally, this study was a single-centered observational study, and all except one was Japanese.