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Symtuza protease inhibitor regimen maintains viral suppression for a year
Liz Highleyman, 2017-10-13 07:30:00
switched from a multi-pill antiretroviral regimen to the first one-pill,
once-daily regimen that includes a protease inhibitor maintained undetectable viral
load for a year, according to a report at the IDWeek 2017 conference last week
in San Diego.
On September 26 the European Commission approved Janssen's
new coformulation, to be marketed as Symtuza, for
the treatment of HIV for adults and adolescents aged 12 and older. US Food and
Drug Administration (FDA) approval is still pending.
the EMERALD study, also published in the October 6 online edition of The
Lancet, showed that an all-in-one coformulation
containing darunavir (sold separately as Prezista), cobicistat as a booster, and emtricitabine and tenofovir
alafenamide or TAF (the drugs in Descovy)
was non-inferior to a standard regimen containing a boosted protease inhibitor plus
emtricitabine and the older tenofovir disoproxil fumarate or TDF (the drugs in Truvada).
Recommended antiretroviral regimens for
first-time HIV treatment often involve single-tablet regimens, which can
potentially improve adherence, but there are fewer one-pill, once-daily options for second-line therapy. Many
treatment-experienced people who have developed drug resistance may need the
potency, durability and high barrier to resistance offered by protease
EMERALD is a
phase 3 clinical trial evaluating the Symtuza
single-tablet regimen as a switch option for people who have achieved
undetectable viral load on a multi-pill regimen.
The study enrolled 1141 participants in the UK, Europe and the
US. More than 80% were men and the median age was 46 years. They had been living
with HIV for a median of nine years and about 60% had used five or more
previous antiretrovirals. At baseline, they had a viral load below 50 copies/ml
for at least two months. The median CD4 count was high, at approximately 630
cells/mm3. They had normal kidney function, which is a consideration
because tenofovir – especially the older TDF – can cause kidney problems.
Most participants (about 70%) were already using
boosted darunavir in their multi-pill regimen, while 22% were on boosted
atazanavir (Reyataz) and 8% were on
lopinavir/ritonavir (Kaletra). About
15% were already using cobicistat, while the rest were using ritonavir (Norvir) as a booster. Although 15% had a
history of prior virological failure, they could not have prior darunavir
failure or evidence of darunavir resistance mutations.
this open-label study were randomly assigned to either switch to the Symtuza single-tablet regimen (also known as D/C/F/TAF) or
stay on their current combination regimen for 48 weeks. Jean-Michel
Molina of the University of Paris reported 24-week interim results at the IAS
Conference on HIV Science in July, and Joseph Eron of the University of North
Carolina School of Medicine presented 48-week primary results at IDWeek.
At 48 weeks, 94.9% of people who switched to Symtuza maintained an undetectable viral load, as did 93.7% of those who stayed
on their baseline combination regimen. These response rates were statistically
similar, showing that Symtuza was
non-inferior to the multi-pill regimens.
Virological rebound was rare in both study arms, 2.5 vs 2.1%, respectively.
Most people who experienced rebound were able to regain viral suppression
by week 48 without changing therapy. Virological failure rates were also low and similar (0.8 and 0.5%,
respectively) and there were no treatment discontinuations due to virological failure.
Among participants who underwent genotypic testing, no mutations conferring resistance to any study drugs were
Treatment was generally safe and well-tolerated. There were few serious
adverse events (4.6% on Symtuza and 4.8% on the
continued regimens) or discontinuations due to adverse events (1.4 vs 1.3%,
respectively). The most common adverse events were nasopharyngitis (nose and
throat inflammation), upper respiratory tract infections and diarrhoea.
Renal and bone biomarkers were more favourable overall in the Symtuza group compared to the group that
stayed on regimens containing TDF, confirming that the new version of tenofovir
is easier on the kidneys and bones.
Estimated glomerular filtration rate (GFR), a common measure of kidney
function, fell a bit more in the Symtuza arm, attributed to
cobicistat's inhibitory effect on kidney tubule secretion of creatinine;
however, the coformulation looked better when GFR was measured using a
different method. Bone mineral density at the hip and spine increased slightly
in the Symtuza arm while falling slightly
in the continued regimen arm. Blood lipid profiles were slightly less
favourable with Symtuza.
findings from the EMERALD study bring us one step closer to being able to offer
those who live with HIV and struggle with adherence an option that combines the
efficacy and high genetic barrier to resistance of darunavir with the
demonstrated safety profile of tenofovir alafenamide into a single
tablet," Eron said in a Janssen press release.
Symtuza is also
being studied for first-line therapy in the phase 3 AMBER trial, with 48-week
results to be presented at the European AIDS Conference in Milan later this