Although two antiretroviral drug regimens proved about equally effective at suppressing HIV, the Biktarvy
combination pill (bictegravir, emtricitabine and tenofovir alafenamide)
did a better job suppressing hepatitis B virus (HBV) in people with
HIV/HBV co-infection, according to research presented on Friday at the 24th International AIDS Conference (AIDS 2022) in Montreal.
What’s more, Biktarvy appeared to produce deeper responses associated with a functional cure for hepatitis B, Dr Anchalee Avihingsanon of HIV-NAT and the Thai Red Cross AIDS Research Centre reported.
HIV and HBV are transmitted by similar routes and many people carry
both viruses. Worldwide, around 8% of people living with HIV also have
HBV, but this can reach as high as 25% in parts of Asia and Africa.
Avihingsanon noted that emerging HIV epidemics in areas with high
hepatitis B rates are leading to an increasing number of people with
Over years or decades, chronic hepatitis B can lead to
severe liver disease, including cirrhosis, liver cancer and the need for
a liver transplant. People with HIV and HBV co-infection experience
more rapid liver disease progression, on average, and are at increased
risk for serious complications compared to those with hepatitis B alone.
“This is still a very important problem, particularly in Asia, and
the clinical course of hepatitis B in people living with HIV is marked
by accelerated liver disease progression,” International AIDS Society
president-elect Professor Sharon Lewin of the Peter Doherty Institute
for Infection and Immunity in Melbourne said at an AIDS 2022 media
Certain 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 with HIV and HBV co-infection should include such dually active drugs in their regimen.
Antiviral treatment for hepatitis B suppresses HBV
replication, which can reduce liver inflammation and bring liver enzyme
levels back to normal. Treatment can sometimes lead to loss of hepatitis
B antigens and production of antibodies (seroconversion), but this is
much less common. Hepatitis B surface antigen (HBsAg) loss is considered
a functional cure.
The ALLIANCE study compared:
The two study arms therefore differed in the integrase
inhibitors they received (bictegravir or dolutegravir) and in the
version of tenofovir they received (the newer TAF or the older TDF).
This phase III trial enrolled 243 people with HIV/HBV
co-infection, mostly in Thailand, China or Malaysia, who had not
previously been treated for HIV or hepatitis B. Most were men, about 90%
were Asian and the median age was about 32 years. About 80% were
hepatitis B ‘e’ antigen (HBeAg) positive.
At study entry, they had an HIV RNA viral load of 500 or higher and
an HBV DNA viral load of at least 2000. The median CD4 count was quite
low, at approximately 240, and 40% fell below 200. Their HIV was not
resistant to emtricitabine or tenofovir, and they had adequate kidney
function (a criteria for people taking TDF).
Participants were evenly randomised to receive B/FTC/TAF or
dolutegravir plus FTC/TDF. The primary endpoint was HIV and HBV viral
suppression at 48 weeks, with treatment continuing through 96 weeks.
Both regimens were highly effective at suppressing HIV,
as seen in previous studies of people with HIV alone. At 48 weeks, 95.0%
of people taking B/FTC/TAF and 91.0% of those taking dolutegravir plus
FTC/TDF had an HIV viral load below 50. CD4 cell gains were 200 and 175,
HBV viral suppression was less common, and B/FTC/TAF proved superior
to dolutegravir plus TDF/FTC: 63.0% and 43.4%, respectively, had HBV DNA
below 29, a statistically significant difference. 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 has also
higher in the B/FTC/TAF group, 23.3% vs 11.3%, respectively. The latter
difference was statistically significant at 48 weeks, Avihingsanon
Declines in hepatitis B surface antigen were less common: 12.6% in
the B/FTC/TAF arm and 5.8% in the dolutegravir plus FTC/TDF group
achieved HBsAg loss at 48 weeks, and 8.4% vs 3.3%, respectively,
experienced 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 48 weeks.
People taking B/FTC/TAF were more likely than those in the
dolutegravir plus FTC/TDF group (73.3% vs 55.3%, respectively) to
experience ALT liver enzyme normalisation, but again the difference was
not significant at 48 weeks. Seven and four participants, respectively,
experienced ALT flares, bursts of liver inflammation that can be a
precursor to HBsAg loss.
Looking at 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 the criteria for resistance testing. One person in the
latter group had NRTI resistance, but none showed evidence of integrase
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% vs 27%, respectively),
as were severe laboratory abnormalities (34% vs 31%).
The most common drug-related adverse event in both groups was weight
gain, reported by 6% and 7%, respectively. This is noteworthy because in
prior studies TAF has been linked to weight gain and TDF to weight
loss. Total and LDL cholesterol increases were uncommon, but seen more
often in B/FTC/TAF group.
Severe 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 therapy due to treatment-emergent adverse events.
Based on these results, the researchers concluded that initial
treatment with B/FTC/TAF was non-inferior to dolutegravir plus FTC/TDF
when it came to HIV suppression. B/FTC/TAF was associated with a higher
rate of HBeAg seroconversion, with numerically higher but not
statistically significant differences in HBeAg loss, HBsAg loss or
seroconversion and ALT normalisation.
B/FTC/TAF “is a safe and effective treatment” for people with HIV and HBV co-infection, Avihingsanon said.
Commenting on the findings, Lewin noted that HBeAg seroconversion is
one marker of successful hepatitis B treatment. “These are important
findings not just for people living with HIV but for hepatitis B
management more generally.”