Symtuza as effective as multi-pill combination in previously untreated people with HIV

Chloe Orkin presenting at EACS 2017. Image credit: Francesc Martínez,

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 (tenofovir disoproxil) in previously untreated people with HIV, Professor Chloe Orkin of the Royal London Hospital reported at the 16th European AIDS Conference (EACS 2017) 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 tenofovir disoproxil.


control group

A group of participants in a trial who receive standard treatment, or no treatment at all, rather than the experimental treatment which is being tested. Also known as a control arm.


A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

resistance testing

Laboratory testing to determine if an individual’s HIV strain is resistant to anti-HIV drugs. 


A rash is an area of irritated or swollen skin, affecting its colour, appearance, or texture. It may be localised in one part of the body or affect all the skin. Rashes are usually caused by inflammation of the skin, which can have many causes, including an allergic reaction to a medicine.

not significant

Usually means ‘not statistically significant’, meaning that the observed difference between two or more figures could have arisen by chance. 

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 control regimen.

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 emtricitabine.

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 (p < 0.001) 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 = 0.18). 


Orkin C et al. Week 48 results of AMBER: A Phase 3, randomised, double-blind trial in antiretroviral treatment (ART)-naïve HIV-1 infected adults to evaluate the efficacy and safety of the once-daily, single-tablet regimen (STR) of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) versus darunavir/cobicistat (DRV/c) plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). 16th European AIDS Conference, 25-27 October, Milan, abstract PS8/2, 2017