Medically Reviewed by Jonathan E. Kaplan, MD on May 30, 2024
4 min read

If you’re living with HIV,  there are now nine types of antiretroviral therapy (ART) that your doctor may prescribe medication AMong the most common are those called non-nucleoside reverse transcriptase inhibitors, also known as NNRTIs. While this sounds like a complicated name, the way these drugs treat HIV is simple to break down. An NNRTI gets in the way of the virus’ ability to reproduce and affect new cells.

You might also hear these drugs called non-nucleoside analogs or non-nukes.

NNRTIs are a type of antiretroviral medication, also known as ARVs. ARVs are commonly used in HIV treatment. There are six types of ARVs.

NNRTIs are always prescribed along with another prescription drug, or as part of a combination drug that also includes other medication.

Before prescribing them, your doctor will consider your health background and situation, including:

  • Which strain of HIV you have and whether there is a chance that your virus is resistant to NNRTIs
  • Other illnesses you may have
  • Other medications you’ve taken in the past or are taking now
  • Your personal preferences

Your doctor should also test you before starting treatment to see if you’re resistant to ARVs.

There are a few NNRTIs your doctor may prescribe:

To understand how an NNRTI prevents the virus from reproducing, you need to know a little about how the virus spreads

Normally, the HIV virus infects cells in your immune system called CD4 cells or T cells. To keep spreading, it needs to keep infecting more cells. The virus first attaches itself to a “host” cell. It then converts its genetic makeup (RNA) into DNA, which is incorporated into the DNA of the host cell. This process allows the virus to replicate.

That’s where the NNRTI comes in. The medication gets in the way of the cell-copying process and their transformation into new DNA. It does this by blocking an enzyme, called reverse transcriptase, that the virus needs in order to replicate. Specifically, it bends the virus’ copying mechanism out of shape.

To enable the NNRTI to do this effectively, you need to take it properly. These medications come in tablets you take by mouth or in a shot you get at your doctor’s office. Carefully follow your doctor’s instructions for your particular NNRTI.

Much of an NNRTI’s effectiveness relies on sticking to your treatment schedule. This is not a drug you can pause or stop taking. It’s best if you don’t miss a dose. Taking it improperly or stopping treatment could affect how well it works in the future. Your body could even become resistant to the medication.

Be honest with your doctor about how well you stick to your routine. Tell them if you’re having trouble with your treatment plan.

To help yourself stick to your medication schedule:

  • Organize your medication with a pillbox that has compartments. for each day of the week.
  • Keep track of your routine into your planner or calendar.
  • Set up digital alarms or reminders for when it’s time to take your NNRTI.
  • Ask your doctor’s office to send you text or email reminders.

A few other things could cause your body to develop resistance to an NNRTI. When the HIV virus replicates, the new copy could be different than the last.

This is called mutation, and it can sometimes happen even if you’re taking one or more ARVs. These mutations could cause the virus to be partially or completely resistant to your medication. This is a possibility with all AVRs, not only NNRTIs. But it doesn’t happen when the virus is at undetectable levels. That’s one reason you should take your medications exactly as prescribed.

Resistance to ARVs can also happen through something called primary resistance. This happens if you get an HIV strain that’s resistant to ARV medications before you’re even prescribed an NNRTI. This is a common problem and could be long term. Transmission of a virus-resistant strain is also a concern when you’re pregnant, as it could be passed to a baby.

It’s also a possibility if you took HIV medications before you contracted the virus. It’s uncommon, but it can happen if you took pre-exposure prophylaxis, also known as PrEP.

If your doctor thinks you may have developed drug resistance during treatment, they’ll do tests to check. They can usually find another medication that will work for you.

If you’re going to have complications or side effects, these usually happen within the first 6 weeks you take an NNRTI. Side effects usually go away as you keep taking the medication. They include digestive issues such as:

  • Diarrhea
  • Vomiting
  • Nausea
  • Upset stomach

Other side effects include headache and rash. If you have a rash that’s serious, tell your doctor right away.

Tell your doctor If you’re using a hormonal birth control pill or patch. NNRTIs may interfere with how well they work. You may need to switch birth control methods or use an additional one to prevent pregnancy. Talk to your doctor about what form is best for you.

There are also potential complications to think about if you’re prescribed an NNRTI. This medication could cause serious liver problems. Tell your doctor if you have hepatitis, preexisting liver problems, or kidney problems. Also, call your doctor if you take an NNRTI and have:

  • Symptoms of jaundice, which makes your skin and eyes look yellow
  • Flu-like symptoms
  • Unusual tiredness
  • Dark urine
  • Lighter stools
  • Discomfort or sensitivity under your right ribs