Long-term TAF works against resistant HBV, poses no excess cardiovascular risk

Tenofovir alafenamide (TAF) shows sustained safety and efficacy in heavily pretreated patients with multidrug-resistant hepatitis B virus (HBV) through 3 years of treatment, albeit leading to elevations in cholesterol levels.

Nevertheless, the potential for future cardiovascular (CV) risk, as assessed by 10-year atherosclerotic CV disease (ASCVD) risk scores that incorporate fasting lipid changes, is low and does not differ relative to tenofovir disoproxil fumarate (TDF).

The above findings from two separate studies were presented at the American Association for the Study of Liver Diseases (AASLD) virtual annual meeting.

In the first study, which involved patients with HBV resistant to multiple drugs (lamivudine, entecavir, and/or adefovir), the viral suppression rates (serum HBV DNA <60 IU/mL) over 144 weeks of treatment were higher among those who continued TAF than those who switched from TDF to TAF (98.9 percent vs 95.4 percent; p=0.99), reported Dr Jonggi Choi of the University of Ulsan College of Medicine in Songpa-gu, Seoul, South Korea. [AASLD 2021, abstract 812]

Furthermore, the three patients who failed to achieve virological response had very low HBV DNA levels at week 144 (180, 86, and 149 IU/mL, respectively), he added.

Choi and his team previously showed that monotherapy with TAF for 48 weeks had noninferior efficacy to TDF in multidrug-resistant HBV. In the current analysis, they looked at the long-term efficacy and safety of prolonged TAF monotherapy. [Clin Gastroenterol Hepatol 2021;doi:10.1016/j.cgh.2021.04.045]

The population included 174 patients who had been under TDF for 96 weeks prior to enrolment and then randomized to switch to TAF (n=87) or continue TDF (n=87) for 48 weeks. Afterwards, the patients on TAF continued with their regimen (TAF-TAF group; n=87) and those on TDF switched to TAF (TDF-TAF group; n=85) through week 144.

Sustained renal and bone safety benefits were observed through week 144, Choi said. The change in estimated glomerular filtration rate from baseline to week 144 was similar in the TAF-TAF and TDF-TAF groups (0.9 percent vs –0.9 percent; p=0.33), as was the improvement in bone mineral density at the spine (3.0 vs 2.1; p=0.21).

Total and low-density (LDL) and high-density lipoprotein (HDL) cholesterol levels increased over 24 weeks after switching from TDF to TAF in both groups (p<0.001 for all). However, according to Choi, there was no further change documented over up to 144 weeks of TAF treatment.

No excess 10-year ASCVD risk

“While TDF has a known lipid lowering effect, TAF is associated with small increases in some parameters (LDL, triglycerides), decreases in HDL (less than with TDF), and has minimal impact on ratio of total cholesterol to HDL,” said Dr Scott Fung of Toronto Centre for Liver Disease in Canada who discussed the results of the second study.

However, in their analysis of data from two large global phase III studies (Study GS-US-320-0108 and Study GS-US-320-0110), Fung and colleagues saw that 2 years of TAF treatment did not increase the mean 10-year ASCVD risk scores compared with TDF. [AASLD 2021, abstract 771]

At baseline, the median 10-year ASCVD risk was low (<5 percent) and similar between TAF and TDF (2.1 percent vs 2.6 percent). The risk remained low at week 96, with no significant between-group differences found in median change in 10-year ASCVD risk score (5 percent for both) and in the shifts in risk categories (eg, from low to intermediate or high risk), Fung noted.

The total study population comprised 1,632 chronic HBV patients aged 40–79 years who were randomized to receive TAF 25 mg (n=1,093) or TDF 300 mg (n=539) daily for at least 96 weeks, after which patients were eligible for open-label TAF through an extension phase.

There were 620 patients (60 percent male, 85 percent Asian, mean body mass index 24.8 kg/m²) who met the American College of Cardiology criteria for 10-year ASCVD risk assessment at baseline and at least one follow-up visit and were included in this analysis. At baseline, 52 percent were HBeAg-positive, 15 percent were cirrhotic, and 20 percent, 13 percent, and 10 percent had a history of hypertension, hyperlipidaemia, and diabetes, respectively.

“Based on new (2019) American Heart Association Guidelines, the proportion of patients who became eligible for statins during the study was higher for TAF vs TDF (6 percent vs 1 percent; p<0.001),” Fung pointed out. “However, within the statin-eligible population, few patients had lipid-lowering therapy initiated (5 percent vs 0 percent; p=1.000).”