Single-Tablet HIV-1 Therapy Proves Efficacy, Safety to Standard of Care

A single-tablet regimen (STR) composed of darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg (D/C/F/TAF) has demonstrated non-inferiority in treating HIV-1 positive, virologically suppressed adults, according to new data presented at ID Week in San Diego, California.

In a phase 3 study, EMERALD, D/C/F/TAF was compared to boosted protease inhibitor (PI) plus emtricitabine and tenofovir disoproxil fumarate over 48 weeks and showed equivalency in safety and efficacy. The combination therapy's once-daily regimen could highlight it as an important step in HIV therapies, as stigma and pill burden remains an issue for HIV treatment adherence.

“Adherence is an important part of HIV management. If a person doesn’t take their HIV medication daily or misses a dose, this can lead to medication resistance, or their medication becoming ineffective, and ultimately put their treatment at risk,” Joseph Eron (pictured), MD, a professor of medicine and director of the clinical core at the University of North Carolina Center for AIDS Research, told MD Magazine. “Patients also are at risk for selective non-adherence, meaning missing 1 or 2 medications from a combination regimen, putting the whole regimen at risk for resistance and the patient at risk for virologic non-response. Providing a full regimen in a single tablet avoids selective non-adherence and may limit resistance emergence and virologic non-response.”

The single-tablet could become the only STR approved to treat HIV-1 with the added benefits of darunavir and safety profile of TAF if approved in the US. It received approval in the EU from the European Commission on September 25, 2017, for HIV-1 patients over 40 kg in weight and 12 years of age.

“If approved in the U.S., D/C/F/TAF would be the only complete regimen that may deliver the potential adherence benefit of a once-daily STR with the durability and high genetic barrier to resistance of darunavir and the demonstrated bone and renal safety profile of TAF,” Rick Nettles, MD, the vice president of medical affairs at Janssen’s infectious diseases division, told MD Magazine.

The trial randomized 1141 patients 2:1 to either D/C/F/TAF (n=763) or the control group on the PI treatment (n=378). In order to be included, patients needed to have a history of virologic failure on darunavir and absence of resistance associated mutations (RAMs) with darunavir, if possible. The primary outcome was to measure virologic rebound, defined as a viral load of ≥50 c/mL or premature discontinuations with last viral load ≥50 c/mL.

Through the 48-week period, the D/C/F/TAF group showed a 2.5% cumulative virologic rebound (n=19) compared to 2.1% in the control group (n=8). In the D/C/F/TAF group, 12/19 were re-suppressed (<50 c/mL) compared to 4/8 in the control.

Virologic suppression in the D/C/F/TAF arm was 94.9% after 48 weeks compared to 93.7% in the control arm. Virologic failure occurred in 0.8% and 0.5% of the D/C/F/TAF and control arms, respectively. No discontinuations for virologic failure or RAMs to any drug occurred.

The safety profile of D/C/F/TAF held up to the control as well, with discontinuations due to adverse events (Res) limited to 1.4% in the D/C/F/TAF group and 1.3% in control. Serious AEs occurred in 4.6% and 4.8% of the arms, respectively, and no deaths were recorded.

Janssen, the manufacturer of the drug, filed a New Drug Application (NDA) with the US Food and Drug Administration (FDA) on September 22, with a PDUFA date expected for mid-2018, according to Nettles.

“The EMERALD study brings 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 safety profile of tenofovir alafenamide into a single tablet,” Eron said.