Rates of sustained viral suppression are similar between single-tablet bictegravir/emtricitabine/tenofovir alafenamide and two-tablet dolutegravir plus emtricitabine/tenofovir disoproxil fumarate in people with HIV-1 and HBV coinfection
Presenter: Anchalee Avihingsanon, MD, HIV-NAT, Thai Red Cross AIDS Research Centre and Centre of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Week-96 results of ALLIANCE, a phase 3, randomized, double-blind study comparing bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (DTG+F/TDF) in treatment-naïve people with both HIV-1 and hepatitis B. Presented July 24, 2023.
Treatment with either a fixed-dose combination of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (DTG+F/TDF) resulted in high rates of sustained HIV-1 and HBV viral suppression in treatment-naïve adults who had both HIV-1 and hepatitis B virus (HBV) infection, according to extended follow-up of the phase 3 ALLIANCE trial. Higher rates of loss of HBV e antigen (HBeAg) (functional cure) and seroconversion were documented in individuals assigned to B/F/TAF compared with DTG+F/TDF over the course of the study.
“International guidelines recommend a TDF- or TAF-containing antiretroviral regimen for most adults with HIV-1/HBV coinfection, but no randomized studies have compared these approaches in this population,” said presenter Anchalee Avihingsanon, MD, HIV-NAT, Thai Red Cross AIDS Research Centre and Centre of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
ALLIANCE is an ongoing randomized, double-blind, multicenter, noninferiority phase 3 study of the single-tablet regimen of B/F/TAF (50/200/25 mg) versus DTG (50-mg tablet once daily) plus F/TDF (200/300-mg tablet once daily) as initial treatment for adults with HIV-1/HBV confection. Study drugs were taken regardless of food intake. In the primary analysis at week 48, B/F/TAF demonstrated noninferiority to DTG+F/TDF in lowering HIV-1 RNA levels to less than 50 copies/mL (95% vs 91%) and superiority to DTG+F/TDF in lowering HBV DNA levels to less than 29 IU/mL (63% vs 43%).
The data presented here were from a prespecified secondary analysis through 96 weeks of follow-up. A total of 243 adults from 46 sites internationally with HIV-1 and HBV coinfection with no previous HIV-1/HBV treatment were randomized 1:1 to daily oral B/F/TAF or DTG plus F/TDF (plus corresponding placebos). More than half (52%) of study participants had a high HBV viral load (> 8 log10 IU/mL) and 78% were HBeAg-positive at baseline. Thirty percent had HIV-1 RNA levels greater than 1,000,000 copies/mL, and 11% had CD4 counts lower than 50 cells/µL.
The rates of HIV-1 RNA and plasma HBV DNA suppression were high with both treatments. At week 96, 87% of participants randomized to B/F/TAF and 88% randomized to DTG+F/TDF achieved HIV-1 RNA levels less than 50 copies/mL, and 75% and 70%, respectively, achieved undetectable HBV viral load (< 29 IU/mL.) The mean increase from baseline in CD4 cells was similar between the two groups: 261 cells/µL in the B/F/TAF arm and 229 cells/µL in the DTG+F/TDF arm, representing changes of 10.7% and 10.4% from baseline, respectively.
The rates of HBeAg loss (38% vs 20%; P = .0064) and HBeAg seroconversion (32% vs 15%; P = .0084) at week 96 were significantly higher in the B/F/TAF arm than in the DTG+F/TDF arm. The proportion of participants with hepatitis B surface antigen (HBsAg) loss at week 96 was 23% in the B/F/TAF arm and 14% in the DTG+F/TDF arm, a difference that was not statistically significant (P = .066). The rate of HBs seroconversion did not differ between the two groups, at 9% in the B/F/TAF group and 7% in the DTG+F/TDF group (P = .44).
There were no differences in the mean reduction in HBV DNA concentrations between groups at weeks 48 and 96, nor in the proportions of patients who had achieved HBV suppression at week 96.
The rate of alanine aminotransferase normalization was numerically greater with B/F/TAF versus DTG plus F/TDF, although not statistically significant (72% vs 57%; P = .13) over 96 weeks.
Any grade -3 or -4 adverse event occurred in 18% of the B/F/TAF arm and 17% of the DTG+F/TDF arm. Serious adverse events were recorded in 14% and 13%, respectively. The rates of other safety endpoints were also similar between groups.
“These data, combined with the lower impact of TAF versus TDF on bone and renal health, show clinical benefits of the single-tablet regimen B/F/TAF for adults with both HIV-1 and HBV initiating antiviral therapy,” concluded Dr. Avihingsanon.
The ALLIANCE trial was funded by Gilead Sciences.
Dr. Avihingsanon reported grants and honoraria from Gilead Sciences; speaker honoraria from ViiV Healthcare and GlaxoSmithKline; and grants, speaker honoraria, and consulting fees from Viatris.