About Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
Medically reviewed by Alan Carter, PharmD on May 10, 2019 — Written by Kathleen Yoder
Drug list
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.
HIV can't be cured, but it can often be controlled.
Treatment with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) is one way to help stop the virus from replicating and control HIV infection. Here's what NRTIs are, how they work, and the side effects they can cause.
How HIV and NRTIs work
NRTIs are one of six classes of antiretroviral drugs used to treat HIV. Antiretroviral drugs interfere with the ability of a virus to multiply or reproduce. To treat HIV, NRTIs 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 the 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.
NRTIs prevent the virus's reverse transcriptase from accurately copying its RNA into DNA. Without DNA, HIV can't make copies of itself.
Available NRTIs
Currently, the Food and Drug Administration (FDA) has approved seven NRTIs for HIV treatment. These drugs are available as individual drugs and in various combinations. These formulations include:
zidovudine (Retrovir)
lamivudine (Epivir)
abacavir sulfate (Ziagen)
didanosine (Videx)
delayed-release didanosine (Videx EC)
stavudine (Zerit)
emtricitabine (Emtriva)
tenofovir disoproxil fumarate (Viread)
lamivudine and zidovudine (Combivir)
abacavir and lamivudine (Epzicom)
abacavir, zidovudine, and lamivudine (Trizivir)
tenofovir disoproxil fumarate and emtricitabine (Truvada)
tenofovir alafenamide and emtricitabine (Descovy)
Tips for usage
All of these NRTIs come as tablets that are taken by mouth.
Treatment with NRTIs usually involves taking two NRTIs as well as one drug from a different class of antiretroviral drugs.
A healthcare provider will select treatment based on test results that give important information about a person's specific condition. If that person has taken antiretroviral drugs before, their 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 manage cases of 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 the 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 a free app that can give reminders when it's time to take the medication. A search for "reminder apps" will provide many options. Here are a few to try.
Ask a family member or friend to give reminders for take the medication.
Arrange to receive text or phone messaging reminders from the healthcare provider.
Potential side effects
NRTIs can cause side effects. Some side effects are more common than others, and these drugs can affect different people differently. Each person's reaction depends in part on which drugs their healthcare provider prescribes and what other drugs that person takes.
In general, newer NRTIs, such as tenofovir, emtricitabine, lamivudine, and abacavir, cause fewer side effects than older NRTIs, such as didanosine, stavudine, and zidovudine.
Types of side effects
Common side effects usually go away with time. These can include:
However, certain severe side effects have been reported. Rare side effects can include:
severe rash
decreased bone density
new or worsened kidney disease
hepatic steatosis (fatty liver)
lipodystrophy (abnormal distribution of body fat)
nervous system effects, including anxiety, confusion, depression, or dizziness
lactic acidosis
Although these side effects aren't common, it's important to know that they can occur and to discuss them with a healthcare provider. Some side effects can be avoided or controlled.
Anyone who experiences these severe side effects should contact their healthcare provider immediately to determine whether they should keep taking the medication. They shouldn't stop taking the drug on their own.
Dealing with side effects can be unpleasant, but stopping the medication may allow the virus to develop resistance. This means that the medication may stop working as well to prevent the virus from replicating. The healthcare provider may be able to change the combination of drugs to decrease side effects.
Risk of side effects
The risk of side effects may be higher depending on a person's medical history and lifestyle. According to the NIH, the risk of some negative side effects may be higher if the person:
is female or obese (the only risk that's higher is for lactic acidosis)
takes other drugs
has other medical conditions
Also, alcoholism can increase the risk of liver damage. A person who has any of these risk factors should talk to their healthcare provider before taking NRTIs.
NRTIs are some of the medications that have made HIV management possible. For these important drugs, newer versions cause fewer severe side effects than previous versions, but some side effects may still occur for any of these medications.
It's important for people whose healthcare providers have prescribed NRTIs to stick to their treatment plan to manage HIV. If they have side effects from antiretroviral therapy, they can try these tips for reducing those side effects. More importantly, they can talk to their healthcare provider, who can make suggestions or change their treatment plan to help relieve side effects.
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