What are the nonnucleoside reverse transcriptase inhibitors (NNRTIs) used in the antiretroviral therapy of HIV infection?

Updated: Apr 18, 2019
  • Author: R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP; Chief Editor: John Bartlett, MD  more...
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Answer

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) were introduced in 1996 with the approval of nevirapine. NNRTIs exhibit potent activity against HIV-1; efavirenz, in particular, confers the most significant inhibition of viral infectivity among the NNRTIs. [7]

First-generation NNRTIs include delavirdine (Rescriptor), efavirenz (Sustiva), and nevirapine (Viramune). Second-generation NNRTIs currently include etravirine (Intelence), approved for use in the United States in 2008, and rilpivirine (Edurant) [24] approved in 2011. In May 2017, it was announced that delavirdine has been discontinued in the U.S. with an estimated availability for the 100-mg tablets until October 2018 and for the 200-mg tablets until February 2020.

The highly specific NNRTI, doravirine, was approved by the FDA in 2018. Approval was based on the DRIVE-FORWARD clinical trial (n=766). Patients who were antiretroviral-naïve were randomly assigned to once-daily treatment with doravirine or darunavir 800 mg plus ritonavir 100 mg (DRV+r), each in combination with emtricitabine (FTC)/TDF or abacavir (ABC)/3TC. Treatment with doravirine led to sustained viral suppression through 48 weeks, meeting its primary endpoint of noninferiority compared with DRV+r, each in combination with FTC/TDF or ABC/3TC. At week 48, 84% of the doravirine group and 80% of the DRV+r group had plasma HIV-1 RNA of less than 50 copies/mL. [25]

All NNRTIs exhibit the same mechanism of action. First-generation NNRTIs share similar resistance patterns, whereas etravirine and rilpivirine display a more unique resistance profile. [26] Their pharmacokinetic properties and adverse-effect profiles have important differences.


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