Trial of two tenofovir-containing regimens for HIV/HBV co-infection: Insights from ALLIANCE

The triplet combination of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is as good as dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+F/TDF) in terms of efficacy for HIV control but results in better hepatitis B virus (HBV) outcomes in patients with HIV/HBV co-infection, according to results of the phase III ALLIANCE trial presented at IAS 2022.

“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, [but the] B/F/TAF [combination] result[ed] in superior HBV DNA suppression and significantly more HBeAg seroconversion,” said study author Dr Anchalee Avihingsanon from HIV-NAT, The Red Cross AIDS Research Centre in Bangkok, Thailand.

The multinational* study population comprised 243 adults (median age 32 years, 4.5 percent female, 88 percent Asian) with treatment-naïve HIV-1/HBV** co-infection. They were randomized 1:1, double-blind, to receive B/F/TAF or DTG+F/TDF*** QD.

At baseline, 30 percent had HIV-1 RNA levels >100,000 copies/mL, 40 percent had CD4 levels <200 cells/µL, and 78 percent were HBeAg+. The median HBV DNA level was 8.1 log₁₀ IU/mL.

At week 48, a comparable proportion of patients in the B/F/TAF and DTG+F/TDF groups achieved HIV-1 RNA <50 copies/mL (95 percent vs 91 percent; difference, 4.1 percent, 95 percent confidence interval [CI], -2.5 to 10.8 percent; p=0.21). [IAS 2022, abstract OALBX0105]

Mean CD4 level change from baseline to week 48 was +200 and +175 cells/µL in the B/F/TAF and DTG+F/TDF groups, respectively.

Significantly more patients who received B/F/TAF than DTG+F/TDF achieved plasma HBV DNA levels <29 IU/mL at week 48 (63 percent vs 43 percent; difference, 16.6 percent, 95 percent CI, 5.9–27.3 percent; p=0.0023).

HbsAg loss occurred in numerically more B/F/TAF than DTG+F/TDF recipients (13 percent vs 6 percent; p=0.059), as did HBeAg loss (26 percent vs 14 percent; p=0.055) and normalization of alanine aminotransferase (ALT) levels (73 percent vs 55 percent; p=0.066). HBeAg seroconversion occurred in more B/F/TAF than DTG+F/TDF recipients (23 percent vs 11 percent; p=0.031).

There was no evidence for treatment-emergent resistance to any components of the B/F/TAF regimen. One DTG+F/TDF recipient experienced a Nucleoside Reverse Transcriptase Inhibitor (NRTI) mutation.

Grade 3–4 treatment-emergent adverse events (TEAEs) occurred at a similar rate between B/F/TAF vs DTG+F/TDF recipients (14 percent vs 16 percent), as did serious TEAEs (12 percent each). Five and one percent, respectively, experienced grade 3–4 study drug-related TEAEs. One B/F/TAF recipient discontinued treatment due to TEAEs and there was one death in each group.

The most frequently occurring AEs in B/F/TAF vs DTG+F/TDF recipients were upper respiratory tract infection (17 percent vs 11 percent), COVID-19 (13 percent vs 11 percent), pyrexia (9 percent vs 12 percent), ALT elevations (7 percent vs 11 percent), and nasopharyngitis (11 percent vs 4 percent). All incidents of ALT flares (affecting seven and four patients in the B/F/TAF and DTG+F/TDF groups, respectively) resolved.

“Chronic hepatitis B affects about 8 percent of people with HIV, and HIV/HBV co-infection rates can reach 25 percent in areas where both viruses are endemic. Co-infection worsens morbidity and mortality; people with HIV/HBV co-infection have higher HBV DNA levels and have a higher risk of cirrhosis and liver cancer than people with HBV mono-infection,” said Avihingsanon. As a result, patients with co-infections require treatments that suppress both viruses.  

“B/F/TAF is a safe and effective treatment for people with HIV-1/HBV co-infection,” she concluded, highlighting that the study is ongoing and 96-week outcomes will be assessed.

“The ALLIANCE study findings are very exciting given the superior activity of B/F/TAF on hepatitis B markers,” commented Professor Sharon Lewin, IAS President-Elect and Director of The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia, who was not affiliated with the trial. “These findings not only have implications for people living with both HIV and hepatitis B, but also for the many people living with HBV alone,” she pointed out.