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Week 48 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)
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B/F/TAF Superior to DTG + F/TDF for HBV (With HIV): 48-Week Trial
AIDS 2022, July 29-August 2, Montreal
Mark Mascolini
Coformulated bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) proved superior to dolutegravir (DTG) plus F/tenofovir disoproxil fumarate (TDF) in reaching a hepatitis B virus (HBV) DNA below 29 IU/mL in a 48-week randomized trial of people coinfected with HBV and HIV, mostly in Asia [1]. B/F/TAF also appeared to have other HBV-related advantages over DTG + F/TDF and was noninferior to DTG + F/TDF in pushing HIV RNA below 50 copies.
Guidelines recommend TDF or TAF plus F or lamivudine (3TC) for most people with HBV/HIV. These 4 reverse transcriptase inhibitors are also components of several favored regimens for people with HIV alone. Because there are no randomized trials comparing TDF and TAF regimens in people coinfected with HBV and HIV, an international team planned and conducted the ALLIANCE trial.
ALLIANCE enrolled HBV/HIV-coinfected people with no previous treatment for either virus. They had to have (1) an HIV load at or above 500 copies, (2) HBV DNA at or above 2000 IU/mL, (3) genotypic sensitivity of HIV to F and tenofovir, and (4) estimated glomerular filtration rate (eGFR) at or above 50 mL/min (indicating reasonable kidney function). Researchers randomized participants to B/F/TAF or DTG + F/TDF placebo, or to DTG + F/TDF or B/F/TAF placebo. Primary endpoints were HIV load below 50 copies at 48 weeks by FDA snapshot analysis and HBV DNA below 29 IU/ml at 48 weeks in a missing-data-equals-failure analysis.
Most participants lived in Thailand, followed by China and Malaysia, with smaller clusters in Taiwan, the Dominican Republic, Turkey, Spain, Japan, Hong Kong, the United States, and Korea. The 121 people randomized to B/F/TAF and the 122 randomized to DTG + F/TDF were similar in median age (31 and 32), proportion of Asians (89% and 87%), and median body mass index (22.2 and 21.7 kg/m2). Both the B/F/TAF group and the DTG group had few women (7% and 2%).
At week 48, proportions with HIV RNA below 50 copies were 95.0% with B/F/TAF and 91.0% with DTG + F/TDF, a nonsignificant difference (P = 0.21). But a significantly larger proportion of the B/F/TAF group than the DTG group had HBV DNA below 29 IU/mL (63.0% vs 43.4%, P = 0.0023).
Also at week 48, people randomized to B/F/TAF versus DTG + F/TDF had higher proportions with HBsAg loss (12.6% vs 5.8%), HBsAg seroconversion (8.4% vs 3.3%), HBeAg loss in people positive for HBeAg at baseline (25.6% vs 14.4%), and HBeAg seroconversion (23.3% vs 11.3%, P < 0.05). (None of the other differences were statistically significant at week 48, though some were significant at week 24 or 36.) At week 48, B/F/TAF outdid DTG + F/TDF in alanine aminotransferase (ALT) normalization by AASLD criteria (73.3% vs 55.3%; difference significant at weeks 12 and 24 but not week 48).
Three people in the B/F/TAF arm and 4 in the DTG arm met criteria for resistance testing at week 48. No resistance to any study drug could be detected at that point in people randomized to B/F/TAF. Nucleos(t)ide mutations emerged at weeks 24 and 36 in 1 DTG participant (M184V/I and K70E). That person regained HIV suppression at week 36 and then fell out of the study.
Five people taking B/F/TAF and 1 taking the DTG combination had a grade 3 or 4 treatment-emergent study drug-related adverse event in 48 weeks. One person taking B/F/TAF and none in the DTG arm had a treatment-emergent adverse event leading to discontinuation (hepatocellular carcinoma; later died). Thirty-four people assigned to B/F/TAF and 31 assigned to DTG had any grade 3 or 4 lab abnormality, usually an ALT or aspartate aminotransferase increase.
Reference
1. Avihingsanon A, Lu H, Leong CL, et al. Week 48 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). AIDS 2022, July 29-August 2, Montreal. Abstract OALBX0105.
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