Week 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)


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.