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Long-acting cabotegravir + rilpivirine injection shows good results at 96 weeks
Liz Highleyman, 2017-07-24 10:20:00
Two long-acting injectable
antiretrovirals, cabotegravir and rilpivirine, administered once every 4 or 8
weeks maintained viral suppression in about 90% of people who started therapy with
an undetectable viral load, according to the latest results from the LATTE-2
trial, presented today at the 9th International AIDS Society Conference on HIV
Science (IAS 2017) in Paris, France.
drugs are highly effective if taken as directed every day. But maintaining good adherence over the long term can be challenging, and long-acting injectable
drug formulations could offer an alternative for people facing a lifetime of treatment.
Joseph Eron of the University of North
Carolina at Chapel Hill presented 96-week findings from the LATTE-2
trial, which is evaluating a two-drug maintenance regimen of ViiV Healthcare’s experimental integrase inhibitor cabotegravir
and Janssen’s NNRTI rilpivirine, which is approved as an oral formulation (Edurant, also in the Eviplera and Complera combination pills).
To ensure the basic efficacy and tolerability of this
regimen before testing the injectable formulations, the earlier LATTE-1 trial
evaluated oral cabotegravir plus
rilpivirine as a simplified two-drug
maintenance regimen for people who achieved undetectable viral load using
standard three-drug antiretroviral therapy (ART).
In 2015, David Margolis of ViiV presented 96-week findings from LATTE-1, showing
that 76% of participants who switched to oral cabotegravir plus rilpivirine
maintained viral suppression, compared to 63% of those who stayed on a
three-drug regimen containing efavirenz (Sustiva).
These results laid the groundwork for the phase 2b
LATTE-2 trial, testing long-acting nano-suspension formulations of cabotegravir and rilpivirine given as intramuscular injections in
the buttocks. Injections currently must be
administered by a health care provider, though self-administration is
potentially possible in the future, Dr Eron said.
This open-label study enrolled
309 participants in Europe and North America who were being treated for HIV for
the first time. More than 9% were men, about 80% were white and the median age was 35 years. The median baseline CD4 count was approximately
500 cells/mm3 and nearly one in five had a high HIV RNA level above 100,000
Participants initially started
a three-drug induction regimen of 30mg oral cabotegravir plus
abacavir/lamivudine (the drugs in Kivexa
and Epzicom). After 20 weeks, those with
viral load below 50 copies/ml were randomly assigned to either stay on the same
oral regimen or switch to long-acting cabotegravir and rilpivirine injections;
286 people met this criterion. The latter group received either 400mg cabotegravir plus 600mg rilpivirine
administered every 4 weeks (Q4W), or 600mg cabotegravir plus 900mg rilpivirine given
every 8 weeks (Q8W)
Dr Margolis presented 32-week results from LATTE-2 (the primary endpoint) at the 2016 Conference of Retroviruses and
Opportunistic Infections, showing that 95% of participants who switched to the Q8W injectable
combo and 94% of those treated on the Q4W regimen maintained undetectable viral
load, as did 91% of those who stayed on the oral regimen.
Most participants maintained viral suppression through
two years, Dr Eron reported today. At 96 weeks, 94% of people on the Q8W
injectable combo and 87% on the Q4W regimen still had undetectable HIV RNA,
compared with 84% on the continued oral regimen.
Three people who received injectable cabotegravir and
rilpivirine experienced protocol-defined virological failure: two on the Q8W
injectable regimen (one at week 4, one at week 48), and one on the oral
regimen. No one receiving the Q4W regimen experienced treatment failure. There
were no additional cases of virological failure between week 48 and week 96.
Injectable cabotegravir and rilpivirine were generally
safe and well tolerated. Serious adverse events occurred with similar frequency
in all three treatment groups, but none were considered drug-related. Eleven
people stopped treatment early due to adverse events (2% in the Q8W group, 7% in the Q4W group and 2% on the oral
regimen). Besides injection site reactions, the most frequently
reported adverse events were nose and throat inflammation, diarrhoea and headache.
Almost all participants reported injection site
reactions, but these were usually mild or moderate and transient, lasting an
average of three days. Only two people (less than 1%) stopped treatment early
for this reason. Pain was the most common complaint.
Despite the frequency on injection-site reactions, participants reported
that they were highly satisfied with the long-acting therapy and would like to
continue on it. “I didn’t realize how much they appreciate not having to take pills
and the feeling of freeness of not having to be bound to oral therapy,” Dr Eron
“Long-acting injectable two-drug therapy given either Q8W or Q4W demonstrated
high rates of virologic response and was well tolerated through 96 weeks,” the
Both Q8W and
Q4W week injections maintained cabotegravir levels similar to those seen with
oral dosing. However, because monthly dosing resulted in a slightly lower rate
of virological non-response at week 48, the Q4W regimen is being further
evaluated in ongoing phase 3 studies.
explained that with longer-term follow-up, additional participants on the Q8W
regimen achieved viral suppression. Evaluation of Q8W dosing is going forward
and a phase 3 study is being developed, he told reporters. However,
administration every month allows for more forgiveness if people miss an
of LATTE-2 show that a long-acting injectable antiretroviral regimen has the
potential to be both highly effective and well tolerated over a long period of
time,” Eron said. “These data provide a strong foundation for the ongoing and
planned phase 3 trials which will hopefully lead to an effective, well
tolerated alternative to daily antiretroviral therapy.”
introduction of single tablet medication represented a leap forward in ART
dosing, and long-acting antiretroviral injections may represent the next
revolution in HIV therapy by providing an option that circumvents the burden of
daily dosing,” Margolis added in a press release from The Lancet.