HIV attacks cells within the body’s immune system. To spread, the virus needs to enter these cells and make copies of itself. The copies are then released from these cells and infect other cells. Treatment with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is one way to help stop the virus from replicating and control HIV infection. NNRTIs are also called non-nucleoside analogues or non-nukes.

NNRTIs are one of 6 classes of antiretroviral drugs (ARVs) used to treat HIV as part of antiretroviral therapy (ART). ARVs interfere with the ability of a virus to multiply or reproduce. To treat HIV, NNRTIs work by blocking an enzyme HIV needs to make copies of itself.

Normally, HIV enters certain cells in the body that are part of the immune system. These cells are called CD4 cells or T cells. After HIV enters CD4 cells, the virus begins to copy itself. To do so, it needs to copy its RNA—the virus’s genetic makeup—into DNA. This process is called reverse transcription and requires an enzyme called reverse transcriptase.

NNRTIs prevent the virus’s reverse transcriptase from accurately copying its RNA into DNA. Without DNA, HIV can’t make copies of itself. NNRTIs act in a similar fashion to NRTIs, but in a slightly different location on the same enzyme. By using NRTIs and NNRTIs together, researchers have discovered these two classes of drugs have a synergistic effect (where the combined effect of the drugs is greater than the sum of the effects of the drugs when they are used alone) on reducing HIV replication.


Currently, there are several NNRTIs that the Food and Drug Administration (FDA) has approved for HIV treatment:

NNRTIs are also available in several combination medications. Combination HIV medicines contain 2 or more HIV medicines from 1 or more drug classes.


All NNRTIs come as tablets that are taken by mouth. Your healthcare provider will select treatment based on test results that give important information about your specific condition. If you have taken ARVs before, your healthcare provider will also factor this in when deciding on treatment options.

Once HIV treatment starts, the medication needs to be taken on a daily basis exactly as instructed. This is the most important way to help control your HIV. The following tips can help ensure adherence to treatment:

    • Take the medication at the same time each day.
    • Use a weekly pill box that has compartments for each day of the week. These boxes are available in most pharmacies.
    • Combine taking the medication with a task that is performed every day. This makes it part of your daily routine.
    • Use a calendar to check off the days when medication was taken.
    • Set an alarm reminder for taking the medication on a phone or computer.
    • Download an app that can give reminders when it’s time to take the medication. A search for reminder apps will provide many options.
    • Ask a family member or friend to give reminders for take the medication.
    • Arrange to receive text or phone messaging reminders from your healthcare provider.


NNRTIs can cause side effects. Some side effects are more common than others. Your reaction depends in part on which drugs your healthcare provider prescribes and what other drugs you take.

Common side effects usually go away with time. These can include:

    • Headache
    • Nausea
    • Vomiting
    • Diarrhea
    • Upset stomach

If you are taking an NNRTI and start to have uncomfortable side effects, don’t stop taking the drug without talking to your healthcare provider first. Pausing or changing ARVs can do more harm than good. The medications may become less effective or the virus may become resistant to the drugs altogether. This means the drugs won’t work anymore to treat the virus.


Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are medications that have made HIV management possible. It is important that the appropriate antiretroviral drug (ARV) regimen for HIV treatment is carefully selected, depending on your medical history, other illnesses, prior HIV treatment, stage of infection, and individual preferences.

If your healthcare provider has prescribed NNRTIs it’s important to stick to your treatment plan to manage HIV. If you have side effects from antiretroviral therapy (ART), there are some tips you can try to manage them. More importantly, talk to your healthcare provider for suggestions and recommendations. Your healthcare provider may also change your treatment plan to help relieve side effects.

Reviewed April 2021

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