Changes in Renal Function after Switching from TDF to TAF in HIV-Infected Individuals: A Prospective Cohort Study

Background: Replacing tenofovir disoproxil fumarate (TDF) with tenofovir alafenamide (TAF) is associated with improvements in renal tubular markers in HIV infected individuals, but the impact on estimated glomerular filtration rate (eGFR) remains unclear. Methods: We included all participants from the Swiss HIV Cohort Study who either switched from a TDF to a TAF-containing antiretroviral regimen or continued TDF. We estimated changes in eGFR and urine protein-tocreatinine ratio over time using multivariable mixed effect models. Findings: Of 3'520 individuals, (26·6% women, median age 50 years), 1'664 (47·3%) had an eGFR below 90 mL/min, 194 (5·5%) had an eGFR below 60 mL/min, and 285 (8%) had marked proteinuria defined as a urine protein-to-creatinine ratio ≥50 mg/mmol prior to switch. In patients with a normal renal function at baseline, eGFR decreased physiologically at 18 months irrespective of the use of TDF or TAF (-1·7 ml/min). In those with renal dysfunction at baseline, switching to TAF was associated with an increase in eGFR: 1·5 mL/min (95% CI 0·5 to 2·5) in individuals with a baseline eGFR of 60-89 mL/min, and 4·1 mL/min (95% CI 1·6 to 6·6) in those with a baseline eGFR <60 mL/min. In contrast, eGFR decreased by 5·8 mL/min (95% CI 2·3 to 9·3) with continuous use of TDF in those with a baseline eGFR <60 mL/min. Urine protein-to-creatinine ratio decreased by 6·1 mg/mmol (95% CI 4·3 to 7·8) at 18 months after replacing TDF by TAF. Interpretation: Switching from TDF to TAF leads to improvements in eGFR and urine protein-to-creatinine ratio in patients with renal dysfunction. Funding Statement: This work was funded by the framework of the SHCS, supported by the Swiss National Science Foundation [SNF grant number 177499, SHCS project number 842]. GW was supported by a Professorship from the Swiss National Science Foundation [PP00P3_176944]. Declaration of Interests: BS reports support to his institution for travel grants from Gilead. BL has received travel grants, grants or honoraria from Gilead and ViiV. AC reports no conflict of interest. MC’s institution has received a research grant from ViiV and Gilead and offered expert testimony for Abbvie, MSD, Gilead and Sandoz. HFG has received unrestricted research grants from Gilead Sciences (HIV cure grant) and Roche; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, ViiV and Merck, Sandoz and Mepha. HK reports supports for travel grants from MSD and Gilead. MS reports no conflict of interest. EB reports support to his home institution for advisory boards and/or travel grants from MSD, Gilead Sciences, ViiV, Pfizer, Abbvie and Sandoz. PS reports no conflict of interest. CAF reports no conflict of interest. HF reports unrestricted educational grant supports to his home institution by Gilead Sciences, ViiV, Abbvie, Bristol-Myers Squibb and MSD outside the submitted work. AR reports support to his institution for advisory boards and/or travel grants from Janssen-Cilag, MSD, Gilead Sciences, Abbvie, and Bristol-Myers Squibb, and an unrestricted research grant from Gilead Sciences. All remuneration went to his home institution and not to AR personally, and all remuneration was provided outside the submitted work. GW reports support to his home institution for advisory boards and/or travel grants from MSD, Gilead Sciences and Abbvie, and an unrestricted research grant from Gilead Sciences. Ethics Approval Statement: Local ethical committees of all cohort centers approved this cohort study and all patients provided a written informed consent.