ETR was considered for inclusion in the regimen in addition to RAL if the genotype indicated low-level or higher resistance to DRV/r, no active NRTIs were available and the ETR MS was <30, particularly if there was no known previous exposure to NNRTIs
Many of the antiretrovirals in common use have been shown to cause a drug-induced hepatitis, including the PIs lopinavir and darunavir, but the most severe reactions have been reported with the NNRTIs
When it is necessary to stop or interrupt a regimen containing an NNRTI
, be aware that the long half-life of the NNRTI
will cause sub-therapeutic levels to persist for up to several weeks.
Predictors of NRTI resistance were gender, age, CD4 count, viral load at failure, dual ZDV+ddI therapy, unboosted and boosted PI, and previous NNRTI
Of the 229 people studied, 108 (47%) began therapy with a PI, 81 (35%) with an NNRTI
, and 40 (18%) with the integrase inhibitor Isentress.
Etravirine (Intelence; Tibotec), a second-generation NNRTI
, requires multiple mutations, and is effective in treating most patients who have failed efavirenz or nevirapine.
Rilpivirine appears to retain antiviral activity against many of the single, double or triple NNRTI
The long half-life of NNRTIs
and their high inhibitory quotients may act as "forgiving" variables allowing for long lasting concentration of the drug in the case of single or sporadic omissions (10).
For those beginning antiretrovirals, the guidelines now say that the combination of an NNRTI
+ didanosine plus tenofovir should not be used, due to virologic failure and development of resistance.
Efavirenz catapulted the NNRTI
class to first-line therapy along with the PIs; its sponsor, Dupont, boldly compared efavirenz to the gold-standard PI, indinavir, in its pivotal study Dupont 006, which demonstrated that efavirenz was as potent as indinavir while being less toxic and, at once rather than 3 times daily, easier to take as well.
This is also the first time the panel has suggested a combination regimen containing an NNRTI
as a preferred first-line treatment option.
M2 PHARMA-July 26, 2017-Merck Study of NNRTI
Doravirine Meets Primary Efficacy Endpoint of Non-Inferiority to Efavirenz for Treatment of HIV-1 Infection