People who 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 26 September the European Commission approved Janssen's new co-formulation, 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.
Findings from the EMERALD study, also published in the 6 October online edition of The Lancet HIV, showed that an all-in-one co-formulation 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 inhibitors.
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.
Participants in 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 observed.
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 co-formulation 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.
"The 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 month.
Orkin C et al. Week 48 results of EMERALD: A phase 3, randomized, non-inferiority study evaluating the efficacy and safety of switching from boosted-protease inhibitors (bPI) plus emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) regimens to the once daily (QD), single-tablet regimen (STR) of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in virologically-suppressed, HIV-1-infected adults. IDWeek, abstract 1689b, 2017. https://idsa.confex.com/idsa/2017/webprogram/Paper67485.html
Orkin C et al. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial. The Lancet, 6 October 2017. http://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(17)30179-0/fulltext