NNRTIs: doravirine, rilpivirine and efavirenz


Doravirine is a once-daily NNRTI that can be taken with or without food. It was approved in 2019 and is also available as part of a single pill Delstrigo with TDF and lamivudine.


Rilpivirine is a once-daily NNRTI that can only be used when viral load is less than 100,000 copies/mL.

Rilpivirine needs to be taken with a solid meal (not a protein drink). It has similar side effects to efavirenz, but they are less common. Rilpivirine is not an option if you have drug resistance to efavirenz or nevirapine.

Rilpivirine is available in two single pill combinations: Eviplera (with tenofovir DF/emtricitabine) and Odefsey (with TAF/emtricitabine). These formulations need slightly less food (about 400 kcal).


Efavirenz is a once-daily NNRTI that was widely prescribed for more than 15 years.

However, since 2015, UK guidelines have recommended using other drugs when starting ART because they have fewer side effects than efavirenz.

The main side effects of efavirenz include mood changes such as anxiety, euphoria and depression, and sleep disturbance that includes vivid dreams and nightmares.

Nearly everyone will get some side effects, but these usually get easier after a few days or weeks. About 10-20% of people stop efavirenz because of this.

Less than 3% of people get severe psychiatric symptoms, but using a different drug is important if this occurs.

If you are worried about these side effects you can use another drug.

Efavirenz can be used during pregnancy and when trying for a baby, even though the information that comes with efavirenz does not say this.

Efavirenz is in the single pill Atripla (with TDF and emtricitabine).

I’d been using efavirenz for years and I always considered myself  lucky. I slept well with no vivid dreams, or obvious depression. But after several years my mental state was going down.

But later, stress at work became unbearable, I had a difficult time sleeping, and I couldn’t shake my depression and anxiety.

Instead of antidepressants, my doctor suggested first stopping efavirenz. Two weeks after switching, everything felt much more manageable.

The difference was unbelievable.

Tim, NYC

Last updated: 1 October 2019.