Tenofovir alafenamide clears hepatitis B faster than tenofovir disoproxil fumarate in multi-country study

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) suppresses hepatitis B (HBV) faster than dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (DTG+F/TDF) in treatment-naive adults co-infected with HIV and HBV, although differences were attenuated by week 96, according to the results of a multinational non-inferiority trial.

About This Study

“Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 and hepatitis B coinfection (ALLIANCE): a double-blind, multicentre, randomised controlled, phase 3 non-inferiority trial“ was published online on July 23, 2023, in the Lancet HIV. The lead author is Anchalee Avihingsanon, M.D., of HIV-NAT at the Thai Red Cross AIDS Research Centre in Bangkok, Thailand, and of the Center of Excellence in Tuberculosis at the Department of Medicine in the Faculty of Medicine at Chulalongkorn University in Bangkok, Thailand.

“Treatment of HIV and HBV coinfection“ is a related commentary by Firouzé Bani-Sadr, M.D., of the Department of Infectious Diseases at the University Hospital of Reims, France. The study was funded by Gilead Sciences, the manufacturer of the study drug, which also contributed to other aspects of the study.

Week 48 results were also presented at the 2023 Conference on Retroviruses and Opportunistic Infections.

Key Research Findings

This multi-country, double-blind, multicenter, randomized controlled, phase 3 non-inferiority trial compared the two tenofovir versions in 243 treatment-naïve HIV/HBV co-infected participants who were randomized 1:1 to take B/F/TAF or DTG+F/TDF. More than 90% of participants were men and 88% of participants were Asian.

At baseline, 30% of participants had HIV viral loads > 100,000 copies/mL and 11% of participants had CD4 cell counts < 50 cells/µL. By week 48, 95% of participants in the TAF arm and 91% in the TDF arm were virally suppressed. By week 96, 87% and 88% of participants, respectively, were virally suppressed.

At baseline, 52% of participants had HBV DNA ≥ 8 log₁₀ IU/mL. By week 48, HBV was suppressed in 63% of participants in the TAF arm and 43% in the TDF arm. By week 96, 75% and 70% of participants, respectively, in the two arms had suppressed HBV. By study end, HBV e antigen (HBeAg) loss was significantly higher in the TAF than in the TDF arm, while hepatitis B surface antigen (HBsAg) loss was similar between the groups.

Discussion Highlights and Implications for Practice

Study limitations reported included participants’ homogenous demographic characteristics (mostly male and Asian), the exclusion of people with decompensated cirrhosis, and insufficient study duration to detect liver disease progression.

There is a need to integrate new HBV biomarkers into care to assess responses to HBV therapies in future trials. In addition, the difference in HBeAg loss between the two tenofovir versions warrants further longitudinal research, Bani-Sadr noted in the associated commentary.

By Barbara Jungwirth