II. Precautions
- NNRTIs carry a high risk of induced HIV resistance
- Never use NNRTIs as monotherapy in HIV Infection
III. Mechanism
- NNRTIs have a completely different mechanism than nRTI (Nucleoside analogs)
- Like nRTIs, NNRTIs bind directly to reverse transcriptase
- Unlike Nucleosides, NNRTIs bind adjacent to the active polymerase site, distorting its active site
- NNRTI binding prevents RNA conversion to DNA
IV. Medications: First Generation
- Efavirenz (Sustiva, EFV)
- Nevirapine (Viramune, NVP)
- Delavirdine (Rescriptor)
- Released in U.S. in 1997 and among the original NNRTI agents
- Less potent than other NNRTIs (e.g. Efavirenz), and is no longer available in the U.S.
V. Medications: Second Generation
-
Doravirine (Pifeltro)
- FDA approved in 2018
-
Etravirine (Intelence)
- Approved in treatment experienced patients
-
Rilpivirine (Endurant)
- FDA approved in 2011 for treatment-naive patients
- Available as oral agent and monthly IM Injection (as part of Cabenuva therapy)
VI. Adverse Effects
- Associated with significant Drug Reactions
- See specific agents
- Hyperlipidemia
- Rash is common (especially with Nevirapine)
- More common and more severe in women
- Reduced Incidence if starting slowly wth reduced dose over 2 weeks
- Prophylaxis not recommended (e.g. Corticosteroids)
- Switching to a different Drug Class may be needed
- May progress to Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, Erythema Multiforme
- Severe rash is especially more common with Etravirine and especially in women
- Neurologic Adverse Effects (esp. Efavirenz)
- Hepatotoxicity
- Hepatotoxicity is a risk with most NNRTIs
-
Hyperlipidemia
- Most common with Efavirenz and Etravirine
-
QTc Prolongation
- Most significant with Efavirenz and Rilpivirine
VII. Drug Interactions
- Many potential Drug Interactions
- Most significant for the long list of interactions with Efavirenz and Etravirine
- See formal Drug Interaction applications
-
Rifabutin
- Second generation NNRTIs require increased dose when concurrently taking Rifabutin
-
Methadone
- Decreased Opioid effect with Nevirapine and Rilpivirine