The single-pill combination of darunavir, cobicistat,
tenofovir alafenamide and emtricitabine (Symtuza) is just as effective as a multi-pill
combination of darunavir, cobicistat, emtricitabine and the older formulation
of tenofovir in previously untreated people with HIV, Professor Chloe Orkin of
the Royal London Hospital reported at the 16th European AIDS
Conference in Milan on Friday.
The combination of darunavir, cobicistat, tenofovir
alafenamide and emtricitabine is already licensed in the European Union as
treatment for HIV infection. The once-daily combination pill is marketed as Symtuza.
The AMBER study was designed to evaluate the safety and
efficacy of Symtuza in previously
untreated people when compared to darunavir/ cobicistat, emtricitabine and an
older formulation of tenofovir (TDF).
The study recruited 725 participants in Europe and North
America predominantly male (88%) and
white (83%) with a median baseline viral load of 4.5 log10 copies/ml
(31,600 copies/ml) and median CD4 cell count of 453 cells/mm3. Seven
per cent had CD4 counts below 200 cells/mm3 and 18% had viral loads
above 100,000 copies/ml.
Baseline drug resistance testing found a high prevalence of
mutations associated with resistance to the non-nucleoside reverse
transcriptase inhibitor drug class (16.3%) suggesting substantial onward
transmission of drug-resistant virus. At least one mutation associated with
protease inhibitor resistance was present in 2.1% of participants at baseline.
Participants were randomised equally to receive Symtuza or the control regimen.
After 48 weeks of treatment 91.4% of the Symtuza group had viral loads below 50
copies/ml compared to 88.4% of the control group, demonstrating the
non-inferiority of Symtuza to the
Virologic failure occurred in 4.4% of the Symtuza group and
3.3% of the control group. No participant experiencing virological rebound
developed resistance to darunavir or tenofovir; one developed resistance to
Discontinuations due to adverse events occurred less
frequently in the Symtuza group (1.9%
vs 4.4%) although the incidence of serious adverse events (4.7% vs 5.8%) and
grade 3-4 adverse events 5.2% vs 6.1%) was similar in the two study arms. The
most common adverse events were diarrhoea, rash and nausea.
Reductions in kidney function as measured by eGFR were
significantly smaller in those treated with Symtuza
than in the control arm after 48 weeks (p0.001) and mean reductions in
spine and hip bone mineral density at weeks 24 and 48 were also significantly
smaller in the Symtuza group.
Participants in the Symtuza study arm had significantly
greater increases in total cholesterol, LDL cholesterol and triglycerides by
week 48 of treatment; but, overall, 1.7% of the Symtuza group needed to start
lipid-lowering therapy compared to 0.6% of the control group, a non
-significant difference (p= .18).