Nucleoside/nucleotide reverse transcriptase inhibitors for HIV

Examples

Generic Name	Brand Name
abacavir	Ziagen
abacavir and lamivudine	Kivexa
abacavir, lamivudine, and zidovudine	Trizivir
didanosine, also known as dideoxyinosine, ddI	Videx
emtricitabine	Emtriva
emtricitabine and tenofovir	Truvada
lamivudine	Heptovir, 3TC
stavudine (d4T)	Zerit
tenofovir disoproxil fumarate	Viread
zidovudine (ZDV), formerly known as azidothymidine (AZT)	Retrovir
zidovudine and lamivudine	Combivir

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 recommended combination is two nucleoside/nucleotide reverse transcriptase inhibitors with one protease inhibitor (PI) or efavirenz (a non-nucleoside reverse transcriptase inhibitor, or NNRTI). Two-PI combinations are also used.

Treatment guidelines suggest the following for people with HIV:¹

• When considering treatment, experts currently consider your CD4+ cell count and the presence or absence of symptoms much more important than your viral load.
• If your CD4+ cell count is between 200 and 350 cells per microlitre (mcL), you should be discussing treatment with your doctor to avoid letting your CD4+ cell count drop below 200.
• If your CD4+ cell count is more than 350 cells per microlitre (mcL), treatment may be offered if you have mild (non-AIDS) symptoms of HIV infection, such as weight loss, fevers, or frequent yeast infections.
• If treatment is not started, your condition will be monitored with frequent CD4+ cell counts.
• If you have symptoms of HIV or AIDS, you should consider starting treatment, whatever your CD4+ cell count is.

Should I start antiretroviral medicines for HIV infection even though I have no symptoms?

Taking antiretroviral medicines for HIV infection

After HIV has progressed to AIDS, treatment is recommended.¹

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 receive ZDV 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.

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

Antiretroviral medicines can cause changes in the distribution of body fats or a more serious side effect called lactic acidosis (too much acid in the blood). Lactic acidosis causes rapid breathing, excessive sweating, cool and clammy skin, sweet-smelling breath, abdominal pain, nausea or vomiting, and coma. In addition, each medicine may be associated with its own unique side effects. Some nucleosides may be associated with lipoatrophy, loss of the layer of fat under the skin of the face, arms, and legs.

Abacavir

A serious, potentially life-threatening allergic reaction occurs in a small number of people who take abacavir. Symptoms of this allergic reaction may include:

• Fever.
• Muscle aches.
• Diarrhea.
• Rash.
• Nausea or vomiting.
• Abdominal pain.
• Severe fatigue.
• Cough.

Didanosine

Side effects of didanosine may include:

• Inflammation of the pancreas (pancreatitis), which can lead to abdominal pain and vomiting. This side effect is more common in people who drink alcohol heavily.
• Numbness, tingling, and painful sensations in the hands and feet (peripheral neuropathy).
• Nausea or vomiting.
• Diarrhea.

Lamivudine

Side effects of lamivudine are uncommon but may include:

• Kidney problems.
• Reduced numbers of red blood cells (anemia).
• Reduced numbers of a certain type of white blood cell (neutropenia).

People who are infected with hepatitis B may have a flare-up of the illness if they suddenly stop taking lamivudine.

Stavudine

Side effects of stavudine may include numbness, tingling, or pain in the hands and feet (peripheral neuropathy). Stavudine also may cause the loss of the layer of fat under the skin of the face, arms, and legs (lipoatrophy).

Tenofovir

Side effects of tenofovir may include nausea or vomiting, diarrhea, or weakness.

Serious side effects of tenofovir can include kidney problems.

Zidovudine

Side effects of zidovudine may include:

• Nausea or vomiting.
• Vague feeling of weakness or discomfort (malaise).
• Headache.
• Reduced numbers of red blood cells (anemia).
• Severe fatigue.
• Insomnia.

Abacavir, zidovudine, and lamivudine combinations

Side effects of any combination of abacavir, zidovudine, and lamivudine include side effects of all three medicines, such as:

• Fever.
• Cough.
• Nausea or vomiting.
• Diarrhea.
• Abdominal pain.
• Severe fatigue.
• Rash.

Emtricitabine

Side effects of emtricitabine can include:

• Headache.
• Diarrhea.
• Nausea.
• Rash.
• Skin discoloration.

Serious side effects of emtricitabine can include severe liver problems.

People who are infected with hepatitis B may have a flare-up of the illness if they suddenly stop taking emtricitabine.

Emtricitabine and tenofovir combination

Side effects of a combination of emtricitabine and tenofovir may include:

• Nausea or vomiting.
• Diarrhea.
• Rash.
• Lack or loss of strength.
• Passing of gas.
• Weight loss.

Report all side effects to your health professional 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.

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Author:	Douglas Dana Maria G. Essig, MS, ELS	Last Updated: October 10, 2007
Medical Review:	Adam Husney, MD - Family Medicine Anne C. Poinier, MD - Internal Medicine W. David Colby IV, MSc, MD, FRCPC - Infectious Disease Peter Shalit, MD, PhD - Internal Medicine
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