12565Week 48 results of a Phase 3 randomized controlled trial of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir + emtricitabine/tenofovir Disoproxil Fumarate (DTG+F/TDF) as initial treatment in HIV/HBV-coinfected adults (ALLIANCE)


A. Avihingsanon * (1), H. Lu (2), C.L. Leong (3), C.-C. Hung (4), E. Koenig (5), S. Kiertiburanakul (6), M.-P. Lee (7), K. Supparatpinyo (8), F. Zhang (9), S. Rahman (10), M. D'Antoni Brogan (10), H. Wang (10), J. Hindman (10), H. Martin (10), J. Baeten (10), T. Li (11) (1) HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand, (2) Shanghai Public Health Clinical Center, Shanghai, China, (3) Department of Medicine, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia, (4) National Taiwan University Hospital, Taipei, Taiwan, Province of China, (5) Instituto Dominicano de Estudio Virologicos - IDEV, Santo Domingo, Dominican Republic, the, (6) Ramathibodi Hospital, Bangkok, Thailand, (7) Queen Elizabeth Hospital, Kowloon, Hong Kong, SAR of China, (8) Chiang Mai University, Chiang Mai, Thailand, (9) Beijing Ditan Hospital, Capital Medical University, Beijing, China, (10) Gilead Sciences, Foster City, United States, (11) Peking Union Medical College Hospital, Beijing, China


BACKGROUND: The clinical course of HBV in individuals with HIV coinfection is marked by accelerated disease progression. A tenofovir-containing anti-retroviral regimen is recommended in most people with HIV-1/HBV-coinfection but there have not been randomized studies of TDF vs TAF in treatment-naïve HIV-1/HBV-coinfected individuals. We report primary endpoint results from a phase 3 study comparing B/F/TAF vs DTG+F/TDF at Week (W) 48 in participants initiating treatment for both viruses.
METHODS: Adults with HIV-1/HBV coinfection were randomized 1:1 to initiate blinded treatment with B/F/TAF or DTG+F/TDF (with placebo). Primary endpoints were proportion of participants with HIV-1 RNA <50 copies/mL (FDA Snapshot) and plasma HBV DNA <29 IU/mL (missing=failure) at Week 48. Noninferiority was assessed with 95% CI (12% margin). Secondary and other endpoints included change from baseline CD4 count, proportion with HBsAg and HBeAg loss/seroconversion, and ALT normalization (AASLD criteria).
RESULTS: 243 participants were randomized and treated (121 B/F/TAF, 122 DTG+F/TDF) from 11 countries in Asia, Europe, North and Latin America. Baseline characteristics were median age 32 years, 4.5% female, 88% Asian, 30% HIV-1 RNA >100,000 c/mL, 40% CD4 <200 cells/mL, median HBV DNA 8.1 log10 IU/mL, 78% HBeAg+. At W48, B/F/TAF was noninferior to DTG+F/TDF at achieving HIV-1 RNA <50 copies/mL (95% vs 91%, difference 4.1%; 95% CI -2.5% to 10.8%, p=0.21), with mean CD4 gains of +200 and +175 cells/mL, respectively. B/F/TAF was superior to DTG+F/TDF at achieving HBV DNA <29 IU/mL (63% vs 43%, difference 16.6%; 95% CI 5.9% to 27.3%, p=0.0023). Participants treated with B/F/TAF vs DTG+F/TDF had numerically higher HBsAg loss (13%, 6%, p=0.059), HBeAg loss (26%, 14%, p=0.055), HBeAg seroconversion (23%, 11%, p=0.031), and ALT normalization (73%, 55%, p=0.066). Most frequent AEs were upper respiratory tract infection (17%, 11%), COVID-19 (13%, 11%), pyrexia (9%, 12%), ALT increase (7%, 11%), and nasopharyngitis (11%, 4%). ALT flares (elevations at '¥2 consecutive post-baseline visits) occurred in 11 participants (7 B/F/TAF, 4 DTG+F/TDF) which resolved.
CONCLUSIONS: In adults with HIV-1/HBV-coinfection starting antiviral therapy, both B/F/TAF and DTG+F/TDF had high HIV-1 suppression at year 1, with B/F/TAF resulting in superior HBV DNA suppression and significantly more HBeAg seroconversion. Safety findings were similar between groups.