NRTIs: Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

About Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)


HIV attacks cells within your immune system. To spread, the virus needs to enter certain cells in your body and make copies of itself. The copies are then released from these cells and infect other cells. HIV can’t be cured, but it can often be controlled.

Treatment with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) is one of the ways to help stop the spreading process and control HIV infection. Here’s what NRTIs are, how they work, and the side effects they can cause, including what makes side effects more likely.

How HIV and NRTIs work

NRTIs are one of six classes of antiretroviral drugs. Antiretroviral drugs interfere with a virus’ ability to copy itself. To treat HIV infection, NRTIs work by blocking an enzyme HIV needs to make copies of itself.

Normally, HIV enters certain cells in your body that contribute to your immune system. These cells are called CD4 cells or T-cells. After HIV enters your T-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.

NRTIs prevent the HIV’s reverse transcriptase from accurately copying its RNA into DNA. Without DNA, HIV can’t make copies of itself and the infection can’t spread.

Available NRTIs

Currently, there are 12 NRTIs that the Food and Drug Administration approves for HIV treatment:


All of these NRTIs come in a tablet that you take by mouth. Treatment with NRTIs usually involves taking two NRTIs as well as one drug from a different class of antiretroviral drugs. Your doctor will base your treatment on test results that give important information about your specific infection. If you’ve taken antiretroviral drugs before, your doctor will also factor that in to decide your treatment options.

Once you start treatment for HIV, you need to make sure you take your medication exactly as instructed. This is the most important way you can help manage your HIV infection. Try these tips to ensure you take your medication correctly:

  • Use a weekly pill box that has compartments for each day of the week. You can find these boxes in most pharmacies.
  • Set an alarm reminder on your phone or computer that reminds you to take your medication.
  • Combine taking your medication with a task you do every day so that it becomes part of your daily routine.

Side effects

You may experience side effects from NRTIs. Some side effects are more common than others, and your body may react differently than another person’s body. Your reaction depends on which drug your doctor prescribes and what other drugs you take.

Each drug also involves a different ingredient or combination of ingredients. Side effects may vary, and the drug ingredients may affect you differently. However, the National Institutes of Health (NIH) suggests that certain side effects are reported with many NRTIs. These side effects can include:

  • decreased bone density
  • new or worsened kidney disease
  • nausea and vomiting
  • hepatic steatosis (fatty liver)
  • lipodystrophy (abnormal distribution of body fat)
  • nervous system effects, including anxiety, confusion, depression, dizziness
  • lactic acidosis

Symptoms of lactic acidosis include:

  • nausea
  • weight loss
  • fatigue
  • rapid heartbeat
  • organ damage

This list of side effects can be alarming, so it’s important to talk to your doctor. Ask them about the specific side effects of the NRTIs that they suggest for you. Some side effects can be avoided or controlled.

If you experience severe side effects, you should remain on the medication until you see your doctor. They may be able to change your combination of drugs to decrease your side effects. Dealing with side effects in the meantime is unpleasant, but stopping the medication may allow the virus to develop resistance. This means that your medication may stop working as well to prevent the virus from spreading.

Your risk of side effects may be higher depending on your medical history and lifestyle. According to the NIH, your risk of some adverse side effects may be higher if you:

  • are female or obese (additional risk only for lactic acidosis)
  • take other drugs
  • have another condition

For example, alcoholism can increase your risk of liver damage. If you meet any of these risk factors, talk to your doctor about the risk to your safety before taking NRTIs.


HIV management has improved since the first NRTI drugs were developed. These drugs interfere with HIV replication so that the virus can’t spread in your body. Current NRTIs have fewer toxic side effects than previous versions. Still, some side effects may happen. If you have side effects, talk to your doctor and stick to their treatment plan. You can also try these tips for reducing antiretroviral side effects.

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