Switching from TDF to TAF in chronic HBV does not worsen renal function, BMD
Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) did not result in worsening renal function or bone mineral density (BMD) in Asian patients with chronic hepatitis B virus (HBV) infection, according to a small real-world prospective study.
“The improvement in proximal renal tubular function and BMD shown at week 12 was sustained through week 72, confirming the improved safety profile of TAF in patients previously treated long-term with TDF,” said the authors.
Participants were 61 Asian adults (median age 57 years, 59 percent male) with chronic HBV (HBV DNA <20 IU/mL for >6 months) who had received TDF for ≥12 months (median 56 months) who attended the Asian Pacific Liver Center (APLC) in Los Angeles, California, US. The patients were switched from TDF to an oral TAF regimen (25 mg QD) and were followed up for 72 weeks.
Patients with co-existing HIV or hepatitis C infection, a history of organ transplantation, and those previously treated with adefovir were excluded. There was no pre-existing or new incidence of decompensated liver disease during the study.
Fifty-nine percent of patients (n=36) had normal renal function at baseline (glomerular filtration rate [GFR] >90 mL/min), while 31 and 10 percent had GFRs of 60–90 and 30–59 mL/min, respectively. There was a decline in creatinine clearance by week 72 compared with baseline (90.9 vs 96.3 mL/min; p<0.01) and compared with week 24 (94.4 mL/min; p<0.05). [JGH Open 2020;5:258-263]
Among patients who had stage 1 chronic kidney disease (CKD) at baseline, 27 remained at stage 1, while nine progressed to stage 2 at 72 weeks. Among those with stage 2 at baseline, one improved to stage 1, two progressed to stage 3, and 16 remained at stage 2. Of those with stage 3 at baseline, five remained at stage 3 and one improved to stage 2.
Markers of proximal tubular function by urine beta-2-microglobulin and urine retinol-binding protein improved between baseline and week 24 (1.5 vs 1.2 μg/g and 1.7 vs 1.5 μg/g, respectively; p<0.01 for both). While the outcomes did not further improve, the improvement was sustained at week 72 compared with baseline (p<0.01).
Urine albumin/creatinine ratio or fractional excretion of uric acid did not change over the 72-week study period. Serum phosphorus and phosphate threshold for renal tubular reabsorption were significantly reduced at week 24 compared with baseline but reverted by week 72.
“Our study suggests that … there may be a “ceiling effect” in recovery after the initial toxicity of TDF,” noted the authors.
Both hip and lumbar spine BMD improved at 24 weeks compared with baseline. The improvement was sustained at 72 weeks for hip BMD (mean 17.7 percent change from baseline; p<0.01), but the improvement in lumbar spine BMD at week 24 (mean change 3.3 percent; p<0.01) decreased to levels similar to baseline by week 72 (-0.6 percent vs baseline; nonsignificant).
Twenty patients were overweight and three obese at baseline. At 72 weeks, 20 patients were overweight and five were obese. Mean body mass index (BMI) increased from 24.1 kg/m2 at baseline to 24.5 kg/m2 at week 24 (p<0.01) and 24.7 kg/m2 at week 72 (p<0.01). The potential effect of TAF on weight gain needs to be assessed in future studies, the authors said.
At week 24, two patients had detectable HBV DNA levels, though this was attributed to lack of adherence to the TAF regimen. “[T]he efficacy of HBV suppression after switching from TDF to TAF remained excellent at 72 weeks of follow-up, with an overall rate of 97 percent,” the authors said.
Post-switch bone and renal safety
“[L]ong-term suppression using potent nucleos(t)ide analogue antivirals remains the mainstay therapy in the treatment of chronic [HBV infection]. Given the need for long-term therapy, an antiviral agent with low risk of long-term drug-related toxicities is imperative,” said the authors.
While TDF is effective in inducing HBV infection suppression with no evidence of resistance, long-term use has been associated with a risk of reduced BMD and renal function. [Dig Dis Sci 2015;60:1457-1464; Dig Dis Sci 2015;60:566-572; Clin Infect Dis 2009;49:1591-1601]
“[Our study showed that] chronic [HBV] patients who switch from long-term TDF to TAF therapy show sustained improvement in proximal tubular function and hip BMD,” they concluded.