Nucleoside/Nucleotide Reverse Transcriptase Inhibitors for HIV

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Nucleoside/Nucleotide Reverse Transcriptase Inhibitors for HIV


Generic NameBrand Name
didanosine, also known as dideoxyinosine, ddIVidex
lamivudine (3TC) 
stavudine (d4T)Zerit
zidovudine (ZDV), formerly known as azidothymidine (AZT)Retrovir

Combination medicines

Generic NameBrand Name
abacavir and lamivudineKivexa
abacavir, lamivudine, and zidovudineTrizivir
emtricitabine and tenofovirTruvada
emtricitabine, efavirenz, and tenofovirAtripla
zidovudine and lamivudineCombivir

These medicines may be available in other combinations to treat HIV infection.

How It Works

Nucleoside/nucleotide reverse transcriptase inhibitors are antiretroviral medicines. They prevent the human immunodeficiency virus (HIV) from multiplying. When the amount of virus in the blood is kept at a minimum, the immune system has a chance to recover and grow stronger.

Why It Is Used

The use of three or more antiretroviral medicines (highly active antiretroviral therapy, or HAART) is the usual treatment for HIV infection.

The combination of medicines used for HAART will depend on your health, other conditions you might have (such as hepatitis), and results of testing. Talk to your doctor about the best treatment plan for you.

Treatment guidelines suggest the following for people with HIV:1, 2, 3, 4

  • When considering treatment, experts currently consider your CD4+ cell count and the presence or absence of symptoms more important than your viral load.
  • If your CD4+ cell count is below 500 cells per microlitre (mcL), treatment is recommended to help keep your immune system healthy and prevent AIDS.
  • If your CD4+ cell count is greater than 500, you may want to consider treatment.
  • If treatment is not started, your condition will be monitored with frequent CD4+ cell counts.
  • If you have symptoms of HIV or AIDS, doctors recommend starting treatment, whatever your CD4+ cell count is.
  • If you are pregnant, you should be treated to prevent your unborn baby (fetus) from becoming infected with HIV.
  • If you also have hepatitis B and are starting treatment for it, you should begin treatment for HIV as well.

You may also want to start HIV treatment if your sex partner does not have HIV. Treatment of your HIV infection can help prevent the spread of HIV to your sex partner.3, 4

Click here to view a Decision Point. HIV: When Should I Start Antiretroviral Medicines for HIV Infection?
Click here to view an Actionset. HIV: Taking Antiretroviral Drugs

Experts recommend one of the following programs for people who begin treatment for HIV:1, 3

  • Efavirenz + tenofovir + emtricitabine
  • Ritonavir-boosted atazanavir + tenofovir + emtricitabine
  • Ritonavir-boosted darunavir + tenofovir + emtricitabine
  • Raltegravir + tenofovir + emtricitabine

Some of the medicines listed above may not be used in some provinces. For information on which medicines are used in your province, talk with your doctor.

Zidovudine (ZDV), either alone or in combination with other antiretrovirals, is recommended for HIV-infected women who are more than 12 weeks pregnant, to prevent HIV from spreading to the fetus. The baby should also receive treatment for 6 weeks after birth.

How Well It Works

Combination therapy:

  • Reduces viral loads, which can lead to stable or increased CD4+ cell counts, a sign that the immune system is still able to fight off opportunistic infections.
  • Decreases the number and severity of opportunistic infections.
  • Reduces or prevents resistance to the medicines.
  • Prolongs life.

Antiretroviral therapy can also reduce symptoms of HIV infection, such as fever, weakness, and weight loss.

Zidovudine (ZDV), either alone or in combination with other antiretrovirals, reduces the risk of the spread of HIV from an infected mother to her baby.1

The rate at which antiretrovirals decrease viral loads is affected by:1

  • CD4+ cell counts at the beginning of treatment.
  • Viral load at the beginning of treatment.
  • The dosage of the medicines.
  • Whether the medicines are taken exactly as prescribed.
  • Whether antiretroviral medicines have been taken before.
  • Whether any opportunistic infections are present.

Side Effects

Side effects of nucleoside/nucleotide reverse transcriptase inhibitors include:

  • Headache.
  • Changes in the distribution of body fat.
  • Nausea, vomiting, and diarrhea.
  • Numbness, tingling, and painful sensations in the hands and feet (peripheral neuropathy).
  • Severe fatigue.
  • Kidney problems.

A serious, potentially life-threatening allergic reaction occurs in a small number of people who take abacavir. A screening test (HLA-B*5701 test) is available to help predict who may have a serious reaction to abacavir.5 The British Columbia Centre for Excellence in HIV/AIDS and the U.S. Department of Health and Human Services (DHHS) recommend that anyone who may receive abacavir should get tested for sensitivity to it first.3, 1

Abacavir also has been linked to an increased risk of heart attack in some people who have other heart attack risks.6

Didanosine may cause inflammation of the pancreas (pancreatitis). This can lead to belly pain and vomiting. This side effect is more common in people who drink alcohol heavily. In rare cases, didanosine can also cause serious liver damage.

Rarely, emtricitabine causes severe liver problems.

People who are infected with hepatitis B may have a flare-up of the illness if they suddenly stop taking certain nucleoside/nucleotide reverse transcriptase inhibitors.

Side effects of any combination medicine can include the side effects of any of the single medicines in the combination.

Report all side effects to your doctor at your next visit. He or she can adjust your dose or give you other medicines to reduce side effects. Some mild side effects, such as nausea, improve as your body adjusts to the medicine.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

Factors to consider when choosing a combination of medicines include:

  • The ability of the medicines to reduce your viral load.
  • The likelihood that the virus will develop resistance to a certain class of medicine. If you have already been treated with an antiretroviral medicine, you may already know whether you are resistant to medicines in that class.
  • Side effects and your willingness to tolerate them.

Many people think that antiretroviral medicines always have severe side effects. In fact, only a few people experience severe side effects.

Complete the new medication information form (PDF) (What is a PDF document?) to help you understand this medication.



  1. U.S. Department of Health and Human Services (2009). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available online:
  2. Hammer, Scott M, et al. (2008). Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society USA Panel. JAMA, 300 (5): 555–570.
  3. British Columbia Centre for Excellence in HIV/AIDS (2011). Therapeutic guidelines—Antiretroviral treatment (ARV) of adult HIV infection. Available online:
  4. U.S. Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents (2011). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available online:
  5. Mallal S, et al. (2008). HLA-B*5701 screening for hypersensitivity to abacavir. New England Journal of Medicine, 358(6): 568–579.
  6. D:A:D Study Group (2008). Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D: study: A multi-cohort collaboration. Lancet, 371(9622): 1417–1426.


By Healthwise Staff
Primary Medical Reviewer E. Gregory Thompson, MD - Internal Medicine
Primary Medical Reviewer Brian D. O'Brien, MD - Internal Medicine
Specialist Medical Reviewer Peter Shalit, MD, PhD - Internal Medicine
Specialist Medical Reviewer Brian D. O'Brien, MD - Internal Medicine
Last Revised May 31, 2011

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