The U.S. Food and Drug Administration has given approval to a coformulation of darunavir 800 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide (TAF) 10 mg, to be marketed under the brand name Symtuza. DRV/COBI/FTC/TAF constitutes a complete regimen for patients with susceptible HIV, and is the first protease inhibitor-containing single-tablet regimen (STR). The approval is specifically for initial HIV treatment and for persons whose HIV is stably suppressed and has no resistance to darunavir or tenofovir. It is to be dosed 1 tablet once daily with food.
Approval was based on results of two Phase 3 studies:
Initial treatment study (AMBER): DRV/COBI/TAF/FTC vs separate tablets of DRV/COBI plus TAF/FTC
Switch study in persons with virologic suppression on a regimen consisting of a boosted PI + TDF/FTC (EMERALD): DRV/COBI/FTC/TAF vs continuation of baseline regimen
In both studies, treatment with the DRV/COBI/FTC/TAF STR resulted in rates of virologic suppression at 48 weeks that were comparable with those in the control arm.
The EMERALD switch study may be of particular interest to clinicians, because (unusually for switch studies) it enrolled subjects with a history of virologic failure on previous regimens, so long as those failed regimens did not include DRV, and the patients' viruses had no DRV-associated mutations. Notably, patients with mutations to tenofovir and FTC were allowed. Study subjects had been on ART for a median of 6 years, 28% had been on >7 ARVs in the past, and 15% had experienced virologic failure at least once. At 48 weeks, virologic suppression to <50 copies/mL was maintained in 95% of the DRV/COBI/FTC/TAF arm and 94% of the control arm (a nonsignificant difference). For more information, review the Darunavir/Cobicistat/FTC/TAF Single-Pill Combination in Treatment-Experienced Patients: EMERALD Study.
An analysis presented at the recent International AIDS Conference stratified outcomes according to baseline PI (DRV, ATV, or LPV) and baseline boosting agent (ritonavir or cobicistat). No differences were seen in rates of virologic rebound in these subanalyses, and there were no notable differences in rates or types of adverse effects. In the few patients with virologic failure, genotypes showed no resistance to any of the study drugs.
Clinical Bottom Line
DRV/COBI/FTC/TAF is now FDA approved and available at pharmacies in United States. Data support its use in initial therapy, but, perhaps more importantly, data from the EMERALD study also support its use against viruses with resistance to FTC or 3TC, at least in the setting of switching from a stable suppressive boosted-PI + NRTIs regimen. We will need more data and clinical experience to know whether this coformulation is effective in controlling viruses with resistance to both tenofovir and FTC/3TC, or whether it is effective in persons with NRTI resistance and high HIV RNA levels at the time it is started.
Symtuza drug label information.
Girard P-M, Huhn G, DeJesus E, et al. Efficacy and safety of switching from boosted protease inhibitor-based regimens to darunavir/cobicistat/emtricitabine/tenofovir alafenamide for treatment of HIV-1 infection: subgroups analysis by baseline regimen. In: Program and abstracts of the 22nd International AIDS Conference; July 23-27, 2018; Amsterdam. Abstract THPEB056.