Nucleoside/nucleotide reverse transcriptase inhibitors for HIV

Examples

Generic Name	Brand Name
abacavir	Ziagen
didanosine, also known as dideoxyinosine, ddI	Videx
emtricitabine	Emtriva
lamivudine	Epivir
stavudine (d4T)	Zerit
tenofovir	Viread
zidovudine (ZDV), formerly known as azidothymidine (AZT)	Retrovir

Combination medicines

Generic Name	Brand Name
abacavir and lamivudine	Epzicom
abacavir, lamivudine, and zidovudine	Trizivir
emtricitabine and tenofovir	Truvada
emtricitabine, efavirenz, and tenofovir	Atripla
lamivudine and abacavir	Epzicom
zidovudine and lamivudine	Combivir

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}

• 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 350 cells per microliter (mcL), you should begin treatment to stabilize and increase your CD4+ cell count.
• If your CD4+ cell count is more than 350 cells per microliter (mcL), treatment may be offered to help keep your immune system healthy and prevent AIDS.
• 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.

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

HIV: Taking antiretroviral medicines

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.³

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. Also, each medicine may be associated with its own 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.

A screening test (HLA-B*5701 screening test) is available to help predict who may have a serious reaction to abacavir.⁴ The U.S. Department of Health and Human Services (DHHS) recommends that anyone who may receive abacavir should get tested for sensitivity to it first.³

Abacavir also has been linked to an increased risk of heart attack in some people who have other heart attack risks.⁵

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.

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.

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.

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Author:	Maria G. Essig, MS, ELS	Last Updated: April 10, 2009
Medical Review:	Caroline S. Rhoads, MD - Internal Medicine Peter Shalit, MD, PhD - Internal Medicine
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