In our nationwide cohort, switching from TDF to TAF in HIV/HBV-coinfected individuals with renal dysfunction was associated with improvements in eGFR and urinary protein-to-creatinine ratio and led to the maintenance of HIV and HBV viral suppression. In addition, patients with elevated ALT levels experienced significant ALT reductions after switching to TAF. These findings provide strong evidence of the benefits of replacing TDF by TAF in HIV/HBV-coinfected patients with moderate renal dysfunction.
In line with results from previous interventional studies we found high HBV suppression rates 1 year after starting TAF.[7,9] However, earlier studies included mostly individuals with normal renal function and showed modest improvements in eGFR or a lower rate of decline with the use of TAF when compared with TDF. In this study switching to TAF was associated with improvements in renal function, which was most pronounced in individuals with a baseline eGFR below 60 mL/min/1.73 m2. Changes in eGFR were not correlated with improvements in urinary protein-to-creatinine ratios because switching from TDF to TAF led to reductions in proteinuria irrespective of the eGFR at baseline.
One third of our study population had elevated ALT levels at baseline, and the replacement of TDF with TAF was associated with a reduction in ALT levels in this subpopulation, independent of other risk factors. For instance, the association remained similar after excluding individuals on EFV-based ART and after restricting the analysis to individuals who had TDF replaced by TAF without further modifications in their ART regimen. In registrational trials, TAF was associated with faster rates of ALT normalization compared with TDF in HBV-monoinfected and HIV/HBV-coinfected patients.[7,9] However, as all but one individual had a suppressed HBV viral load at baseline in our study, more efficient HBV suppression cannot explain our results. Altogether, these findings raise the possibility that TDF may cause some degree of liver toxicity, which seems to be at least partially reversible after switching to TAF. The potential for liver toxicity of TDF has been observed in a large cohort study of HIV-monoinfected individuals, which found a strong relationship between TDF and elevated transaminases. Further studies are needed to confirm our finding and generate potential explanations.
Our study is among the first to evaluate the benefit of using TAF among HIV/HBV-coinfected individuals with renal dysfunction. The use of interrupted time series allowed us to compare dynamic changes in outcomes between the year before and after the switch, whereas minimizing confounding by variables that remain constant over the course of time. Although selection bias or confounding by indication is possible in cohort studies, we were able to include most patients in all analyses, except in the one focusing on urinary protein-to-creatinine ratio. However, as the main demographic and clinical characteristics of individuals with and without available proteinuria follow-up measurements did not differ significantly, our results remain valid. The robustness of the ALT analyses is challenged by the low number of individuals with elevated levels at baseline, the brief follow-up period of 1 year, and the possibility of a regression to the mean effect. Finally, given that paired baseline and follow-up TE measurements were unavailable for most individuals, the analyses on ALT levels could not be stratified by the underlying degree of fibrosis.
J Acquir Immune Defic Syndr. 2020;85(2):227-232. © 2020 Lippincott Williams & Wilkins