Longer-Term Phase III Data Promising for Single-Tablet Symtuza

GLASGOW, Scotland — The darunavir-based single-drug combination HIV treatment, which includes cobicistat, emtricitabine, and tenofovir alafenamide (Symtuza, D/C/F/TAF) continued to achieve high virological suppression and low rates of failure comparable to controls, a researcher said here.

In week 96, treatment-naïve HIV-infected adults in the D/C/F/TAF arm of the study had virological suppression comparable to controls (85% versus 84%, respectively), reported Chloe Orkin, MD, of Barts Health NHS Trust and Queen Mary University of London.

The week 96 results of the phase III AMBER study were presented at HIV Glasgow, the International Congress of HIV Drug Therapy.

Symtuza was approved by the FDA in July, and phase III results for the AMBER study at 48 weeks were recently published. AMBER was conducted in treatment-naïve adults, while the EMERALD study examined the treatment in adults whose HIV was well controlled. Phase III week 48 results of EMERALD were presented at IDWeek last year, while week 96 results were presented at the conference this year.

“Based on the [Department of Health and Human Services] guidelines, darunavir-based regimens are a recommended option in situations where clinicians may not have all genotypic resistance test results, when patients may be at risk for suboptimal adherence or in rapid initiation scenarios,” said Joseph Eron, MD, of the University of North Carolina Center for AIDS Research in Chapel Hill, in a statement from the manufacturer.

AMBER was a phase III randomized non-inferiority trial. It badessed 725 treatment-naïve adults, with a viral load of ≥1,000 c/mL, CD4 >50 cells/mm³, a genotype susceptibility to darunavir, emtricitabine, and tenofovir, and who were hepatitis B and C negative. At week 48, there was a database lock and unblinding, and patients on control therapy could switch to D/C/F/TAF through the extension phase. Initially, 362 patients were randomized to the intervention arm and 363 to D/C +F/TDF (tenofovir disoproxil fumarate), though 295 were defined as part of the D/C/F/TAF switch.

Overall, participants were a median 34 years old, approximately 85% were men, and about 80% were white. At baseline, 18% had viral load ≥100,000 copies/mL and participants had a median CD4+ count of 453 cells/mm³, the authors said.

Virological suppression in the D/C/F/TAF arm was also comparable among patients with viral load <200 copies/mL (86% versus 86% for controls at week 96). The authors also noted that viral load ≥50 copies/mL occurred in 6% of patients in the intervention group and 4% from baseline in the control group.

Orkin presented subgroup badyses of patients with viral loads <50 copies/mL, although there were "small representation across subcategories, so the confidence intervals are extremely wide," she said.

Some Concerns about Subgroup Analyses

The session moderators, who were not involved with the research, had a few issues with subgroup badyses of patients with viral loads <50 copies/mL. Jonathan Schapiro, MD, of the National Hemophilia Center in Tel Aviv, Israel, pointed out the difference in the number of virologically suppressed patients with a baseline CD4+ <200 cells/mm³ (22 versus 29 in the control group), and asked if anything could be said “with confidence” about this data.

Orkin said that four out of 22 patients were defined as virologic failures (VL >50), but one patient was lost to follow-up, one had adherence issues, and one re-suppressed — meaning there was only one virologic failure.

Giulia Marchetti, MD, of the University of Milan in Italy, also raised concern about “a higher rate of virologic failure in black people.” (70% virologically suppressed in intervention versus 83% of controls).

“With only 40 patients in each arm, it’s easy to see changes,” Orkin said, citing “a very homogenous” study population with under-representation by racial and ethnic minorities, women, older adults, and those with more severe illness.

The authors also noted that there were no darunavir, primary protease inhibitor, or tenofovir resistance badysis mutations seen post-baseline. There were also few serious adverse events and no treatment discontinuations, the team reported, adding that D/C/F/TAF bone, renal, and lipid safety were consistent with known TAF and cobicistat profiles.

One audience member noted the slight change in total cholesterol: HDL-C ratio from week 48 to week 96 in the D/C/F/TAF arm (4.0 to 4.2, respectively), and asked about recent publications documenting increases in body weight with switching to TAF.

Orkin said during the presentation that the clinical relevance of lipid changes would “depend on the status of the patient,” and responded here that “treatment-naïve individuals are more likely to gain weight in the first year, but it’s less clear in a switch study.”

1969-12-31T19:00:00-0500

last updated 10.31.2018