Although two antiretroviral regimens were shown to be equally effective in suppressing HIV, the combination pill Biktarvy (bictegravir, emtricitabine and tenofovir alafenamide) was more successful in suppressing hepatitis B virus (HBV) in co-infected people by HIV/HBV. infection, according to research presented Friday at the 24th International AIDS Conference (AIDS 2022) in Montreal.
“Additionally, Biktarvy appeared to produce deeper responses associated with functional cure of hepatitis B,” said Dr. Anchalee Avihingsanon, HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT – Netherlands Australia Thailand Research Collaboration) and the Thai Red Cross AIDS Research Centre.
HIV and HBV are transmitted by similar routes, and many people carry both viruses. Worldwide, about 8% of people living with HIV are also infected with HBV, but this figure can reach 25% in parts of Asia and Africa. Avihingsanon noted that emerging HIV epidemics in areas with high rates of hepatitis B result in increasing numbers of people co-infected with HIV and HBV.
Over years or decades, chronic hepatitis B can lead to serious liver disease, including cirrhosis, liver cancer, and the need for a liver transplant. People co-infected with HIV and HBV experience faster progression of liver disease, on average, and are at greater risk of serious complications than those with hepatitis B alone.
“This is still a very big problem, especially in Asia, and the clinical course of hepatitis B in people living with HIV is marked by the accelerated progression of liver disease,” said Sharon Lewin, president-elect of the International Aids Society, Peter Doherty Institute for Infection and Immunity in Melbourne (Peter Doherty Institute for Infection) at a press conference on the AIDS Conference 2022.
Some antiretrovirals used to treat HIV – lamivudine, emtricitabine, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) – are also active against HBV. They are components of several widely used antiretroviral co-formulations. Treatment guidelines recommend that people co-infected with HIV and HBV include these dual-action drugs in their regimen.
Antiviral treatment for hepatitis B suppresses HBV replication, which can reduce liver inflammation and return liver enzyme levels to normal. Treatment can sometimes cause the loss of hepatitis B antigens and the production of antibodies (seroconversion), but this is much less common. Loss of hepatitis B surface antigen (HBsAg) is considered a functional cure.
The ALLIANCE study compared:
- bictegravir, emtricitabine and tenofovir alafenamide (B/FTC/TAF or Biktarvy), taken as a single tablet once daily, versus
- dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF; Truvada and generic equivalents), taken as two tablets once daily.
The two arms of the study therefore differed in the integrase inhibitors they received (bictegravir or dolutegravir); the version of tenofovir they received (the most recent TAF or the oldest TDF); and in the load of pills.
This phase III study involved 243 people co-infected with HIV/HBV, mainly in Thailand, China or Malaysia, who had never been treated before for HIV or hepatitis B. The majority were men, about 90% were Asian, and the average age was about 32 years.
About 80% were positive for hepatitis B “e” antigen (HBeAg). At baseline, they had an HIV RNA viral load of 500 or more and an HBV DNA viral load of at least 2000. The median CD4 count was quite low, at around 240, and 40% dropped below 200. Their HIV was not resistant to emtricitabine or tenofovir, and they had adequate kidney function (a criterion for people taking TDF). Participants were also randomized to receive B/FTC/TAF or dolutegravir plus FTC/TDF. The primary endpoint was HIV and HBV viral suppression at 48 weeks, with treatment continued for 96 weeks.
Both diets were highly effective in suppressing HIV, as seen in previous studies involving only people living with HIV. After 48 weeks, 95.0% of people taking B/FTC/TAF and 91.0% of people taking dolutegravir plus FTC/TDF had viral loads below 50. CD4 cell gains were 200 and 175, respectively. . HBV viral suppression was less common, and B/FTC/TAF was found to be superior to dolutegravir plus TDF/FTC: 63.0% and 43.4%, respectively, had HBV DNA less than 29, a statistically different significant. .
The time course of HBV DNA decline was similar in both groups. Among participants who were HBeAg positive at baseline, 25.6% in the B/FTC/TAF arm experienced HBeAg loss at 48 weeks, compared with 14.4% in the dolutegravir plus FTC/TDF group. HBeAg seroconversion was also higher in the B/FTC/TAF group, 23.3% versus 11.3%, respectively. The latter difference was statistically significant at 48 weeks, Avihingsanon reported. Hepatitis B surface antigen declines were less frequent: 12.6% in the B/FTC/TAF group and 5.8% in the dolutegravir plus FTC/TDF group achieved loss of HBsAg at 48 weeks and 8.4% versus 3.3%, respectively, showed loss of HBsAg seroconversion.
Although the rates of HBsAg loss and seroconversion were numerically higher in the B/F/TAF arm, the differences did not reach statistical significance at week 48. People who took B/FTC/ TAF were more likely than those in the dolutegravir group to be more FTC/TDF (73.3% versus 55.3%, respectively) showed normalization of ALT liver enzymes, but again the difference was not significant at 48 weeks. Seven and four participants, respectively, experienced ALT flares, flare-ups of liver inflammation that may be a precursor to loss of HBsAg.
Regarding anti-HIV drug resistance, three people who did not achieve HIV suppression in the B/FTC/TAF group and four in the dolutegravir plus FTC/TDF group met resistance testing criteria. One person in the latter group showed resistance to NRTIs, but none showed evidence of resistance to integrase inhibitors. The treatment was generally safe and well tolerated, Avihingsanon said.
The frequency of drug-related adverse events was similar in the B/FTC/TAF and dolutegravir plus FTC/TDF arms (24% versus 27%, respectively), as were serious laboratory abnormalities (34% versus 31%). The most common drug-related adverse event in both groups was weight gain, reported by 6% and 7%, respectively. This is remarkable because in previous studies, TAF was associated with weight gain and TDF with weight loss. Increases in total cholesterol and LDL cholesterol were uncommon but observed more frequently in the B/FTC/TAF group.
Serious drug-related adverse events were rare in both groups, 5% and 1%, respectively. Only one person with liver cancer in the B/FTC/TAF arm discontinued treatment due to treatment-emergent adverse events. Based on these results, the researchers concluded that initial treatment with B/FTC/TAF was not inferior to dolutegravir plus FTC/TDF in suppressing HIV. B/FTC/TAF was associated with a higher rate of HBeAg seroconversion, with numerically larger, but not statistically significant, differences in HBeAg loss, HBsAg loss, or seroconversion and ALT normalization.
B/FTC/TAF “is a safe and effective treatment” for people co-infected with HIV and HBV, Avihingsanon said. Commenting on the results, Lewin noted that HBeAg seroconversion is a marker of success in the treatment of hepatitis B. “These are important results not only for people living with HIV, but for the treatment of hepatitis B in general.”