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Doravirine--New NNRTI Approved by FDA
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The U.S. Food and Drug Administration has approved the NNRTI doravirine for use in initial HIV therapy. FDA approval was based on 48-week results of 2 Phase III studies in treatment-naive persons that showed doravirine + 2 NRTIs resulted in similar rates of viral suppression at 48 weeks as either efavirenz + 2 NRTIs or darunavir/ritonavir + 2 NRTIs. Recommended dosing is 100 mg once daily, with or without food. Doravirine will be marketed under the brand name Pifeltro. It will be available both as an independent medication and as part of a single-pill combination (SPC) that also includes tenofovir DF and lamivudine; the SPC will be marketed as Delstrigo.

Doravirine generally was well tolerated and did not perturb lipid levels. It should be noted that in Phase III studies, virologic failure on doravirine + 2 NNRTIs sometimes resulted in NNRTI-associated resistance mutations and substantial NNRTI cross-resistance.

Clinical Bottom Line

Doravirine has been approved for initial treatment of HIV, but its potential role as an agent in antiretroviral therapy is not yet clear. Virologic suppression rates in the Phase III studies--while noninferior to those of the comparator ARVs--were much lower than typically is seen in trials of integrase inhibitors in initial therapy, and doravirine has not been compared with integrase inhibitor (our current gold standard for first-line therapy). In addition, coformulated doravirine/TDF/3TC does not appear to have significant advantages over other SPCs, and it has the notable drawback of containing TDF, with its potential renal and bone toxicities.

Doravirine may turn out to be more useful in subsequent lines of therapy, for example as part of a multiclass salvage regimen or a simplification regimen. Clinical data on doravirine's activity after failure of other NNRTIs will be needed to guide use in this setting.

References
Product information available at Drugs@FDA.