Renal Dysfunction Improves Following Switch From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide

By Will Boggs, MD

August 19, 2020

NEW YORK (Reuters Health) - In HIV/hepatitis B virus (HBV)-coinfected individuals with renal dysfunction, renal function improves after switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF), according to results from a prospective study.

"Unlike other HIV-infected individuals, those who are HBV-coinfected need to maintain tenofovir in their antiretroviral therapy (ART) regimen," Dr. Bernard Surial of Bern University Hospital, in Switzerland, told Reuters Health by email. "Thus, our finding that renal function improved after switching to TAF is important and reassuring."

TDF has been associated with renal side effects, and HBV infection can result in kidney injury. By reducing tenofovir plasma concentrations, the prodrug TAF has a favorable renal safety profile compared with TDF. Most studies of the renal safety of TAF in HIV/HBV-coinfected patients, however, mainly enrolled individuals without renal impairment.

Dr. Surial and colleagues in the Swiss HIV Cohort Study evaluated the impact of replacing TDF with TAF on estimated GFR (eGFR), urine protein-to-creatinine ratio, and alanine aminotransferase (ALT) levels in 106 HIV/HBV-coinfected individuals with renal dysfunction at baseline.

Baseline eGFR was between 60-89 mL/min/1.73 m2 in 79.2% of these patients and was below 60 mL/min/1.73 m2 in the rest.

Individuals in the higher-eGFR group experienced decreases in eGFR of 1.9 mL/min/1.73 m2 during their last year on TDF, but experienced increases in eGFR of 3.2 mL/min/1.73 m2 one year after switching to TAF, the researchers report in JAIDS.

Similarly, individuals in the lower-eGFR group saw decreases of 4.9 mL/min/1.73 m2 in the year prior to switching and increases of 6.2 mL/min/1.73 m2 1 year after switching from TDF to TAF.

Among the 58 individuals who had urine protein-to-creatinine ratios available, the use of TDF was associated with a 0.9 mg/mmol increase in the last year prior to switching, and switching to TAF was associated with a 6.3 mg/mmol decrease one year later.

Among patients who had elevated ALT levels while taking TDF, switching to TAF was associated with significant ALT reductions.

"We believe that most patients can safely benefit from the increasing availability of the new and very effective single-pill regimens which are only co-formulated with TAF," Dr. Surial said. "This is especially true for individuals with bone or renal disorders, irrespective of the presence of HBV infection."

"However," he said, "drug-drug interactions should be carefully reviewed, and TAF should not be used in pregnancy due to limited data. The potential for metabolic complications (e.g., worsening of lipid profiles or weight gain) has recently become more apparent, and should be weighed against the benefits of a TAF-based therapy for every patient."

Dr. Tse-Ling Fong of Keck School of Medicine, University of Southern California, in Los Angeles, who recently reported improvements of bone mineral density and markers of proximal renal tubular function in chronic HBV patients switched from TDF to TAF, told Reuters Health by email, "I see no reason why all TDF shouldn't be switched. I don't think TAF has received approval for patients with low GFR (30 mL/min/1.73 m2) or who are pregnant. Until then, these 2 groups are excluded." Dr. Fong was not involved in the new study.

Gilead Sciences funded the trial and had financial ties to several of the authors.

SOURCE: JAIDS, online July 2, 2020.


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