by Liz Highleyman
January 2004 (Reviewed and Revised December 2005)
Zerit – brand name
d4T – commonly-used name
stavudine – generic name
Zerit belongs to a class of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs), also known as nucleoside analogs or “nukes.”
Zerit and the other NRTIs block reverse transcriptase, a protein that HIV needs to make more copies of itself. This may slow down HIV disease.
The Food and Drug Administration (FDA) has approved Zerit for use in combination with other HIV drugs for the treatment of HIV infection in adults and children more than six months old.
The FDA also granted tentative approval of a generic formulation of Zerit. This version is not yet available in the U.S.
Zerit comes in:
- 15 milligram (mg), 20 mg, 30 mg, and 40 mg capsules
Dosing depends on body weight:
- If you weigh more than 132 pounds, the dose of Zerit is 40 mg twice daily
- If you weigh less than 132 pounds, the dose of Zerit is 30 mg twice daily
Zerit XR (extended-release formulation) was FDA approved in 2002, but due to manufacturing issues it will not be made commercially available.
If you have liver, kidney, or pancreas problems, or peripheral neuropathy, your dose may need to be adjusted.
Check with your child’s doctor for children’s dosing.
Zerit must be used with other HIV medications to treat HIV.
You can take Zerit with food or on an empty stomach, but taking it with food may cut down on nausea or other side effects.
As with all HIV drugs, it is important to take Zerit as prescribed. Missing or skipping doses can cause your blood levels of the drug to fall too low and resistance can develop. When your virus becomes resistant to an HIV medication, that drug may stop working.
Zerit can be used if you are beginning treatment for the first time.
You may be able to use Zerit if you have developed resistance to another NRTI.
Your doctor can run a resistance test to help determine whether Zerit is likely to work for you.
Zerit crosses the blood-brain barrier (which protects the brain and spinal cord), so it may be able to fight HIV in the brain.
If your virus develops resistance to Zerit then it may stop working or not work as well for you. You also may not get as much benefit from the other NRTIs.
Sometimes taking more than one medication can cause drug interactions. Taking certain drugs with Zerit can change the amount of each drug in your blood; your doctor may need to adjust the doses of your drugs to avoid under- or overdosing.
Several other medications can make the side effects of Zerit worse, such as Hivid (zalcitabine or ddC) and hydroxyurea. Be sure your doctor knows about all the medications you are taking (including over-the-counter, prescription, street drugs, and herbs), even if you only use them occasionally.
For more information and additional resources to check interactions between the particular drugs you are taking, see our info sheet on drug interactions.
Zerit seems to cause more side effects than many of the other NRTI drugs, especially fat loss in the arms, legs, face, and buttocks (lipoatrophy), peripheral neuropathy, and lactic acidosis. Some of these side effects can be very serious and are more likely to occur if Zerit and Videx EC are taken together.
However, most Zerit side effects are likely to be temporary and go away as your body adjusts to the medication. If you are experiencing any of the side effects listed below, call your doctor for advice. Do not just stop taking your medication.
- Diarrhea or constipation
- Fatigue (unusual tiredness)
- Skin rash
More serious side effects:
- Peripheral neuropathy (numbness, pain, or tingling, especially in your feet and hands).
- Pancreatitis (inflammation of the pancreas) can be a serious threat to your health. Symptoms include sudden or sharp pains in the middle of the abdomen, fever, nausea, or vomiting.
- An increase of lactic acid in the blood (lactic acidosis), an enlarged and fatty liver, and liver failure have been reported in people using NRTIs. Lactic acidosis is a rare but potentially fatal side effect. Symptoms include nausea, vomiting, or stomach pain; feeling very weak and tired; shortness of breath.
- Lipodystrophy, which may include elevated blood sugar (glucose), elevated lipid levels ( cholesterol and triglycerides), and fat gain or loss in certain areas. The exact causes of lipodystrophy are not known, but may include HIV and/or HIV drugs. Zerit may cause more fat loss than other HIV drugs, but it is unclear if Zerit will cause or impact other symptoms of lipodystrophy. For more information on lipodystrophy, see our info sheet.
If you are experiencing persistent, unusual, or serious side effects, call your doctor right away.
Zerit has been studied in both men and women. Its effectiveness and side effects seem very similar for both men and women. But some research suggests that women are more likely than men to develop liver problems while taking NRTI drugs.
Zerit has been studied in many women. The START I trial compared Zerit plus Epivir (lamivudine or 3TC) plus Crixivan (indinavir) to Retrovir plus Epivir plus Crixivan. The START II trial compared Zerit plus Videx plus Crixivan to Retrovir plus Epivir plus Crixivan. In START I, the two regimens worked about equally well, while in START II, the regimen containing Zerit appeared to work slightly better.
Together, these trials included 19 percent women, or about 77 women out of total 409 participants. In a combined analysis of both START trials, researchers found that men responded slightly better to treatment with Zerit than women, but this trend was not statistically significant.
In terms of side effects, several studies have shown that people taking Zerit are more likely to experience loss of fat in the arms and legs (lipoatrophy). In one such trial, a sub-study of ACTG 384, 156 participants (15 percent women – about 23 women) received body scans to determine fat changes. Unfortunately, there were not enough women in this study to determine whether fat loss differed in women and men.
Zerit has also been linked to lactic acidosis (high levels of lactic acid in the blood). The ESS40002 study compared Retrovir plus Epivir plus Ziagen (abacavir) to Retrovir plus Epivir plus Viracept (nelfinavir) or Zerit plus Epivir plus Viracept. This small study was unusual because it included 50 percent women (about 129 women out of 258 total participants), 40 percent African Americans, and 37 percent Latinos.
In this study, women taking Zerit were more likely to develop elevated lactic acid levels. Studies of medical records indicate that women (especially overweight women) taking NRTIs, including Zerit, are more likely than men to develop elevated lactic acid levels and enlarged fatty livers.
Studies have shown that pregnant women who use HIV drugs can greatly reduce the risk of passing HIV on to their babies. Zerit has been used during pregnancy without any significant negative effect to mother or baby; however, long- term effects on the child are not known.
There have been a few cases of fatal lactic acidosis in pregnant women taking Zerit plus Videx EC. In 2001, the FDA issued a warning about use of this drug combination by pregnant women. Pregnant women should not take Zerit and Videx EC together.
Check with your doctor about the best treatment options for you and your baby if you are thinking of getting pregnant.
Click this link for more information about pregnancy.
People who are starting HIV treatment for the first time may develop Immune Reconstitution Syndrome or IRS (also called Immune Reconstitution Inflammatory Syndrome or IRIS). IRS can happen as a result of the immune system getting stronger and responding to an HIV-related infection such as Mycobacterium avium infection (MAC), cytomegalovirus (CMV), Pneumocystis jirovecii pneumonia (PCP), or tuberculosis (TB). People may have been treated for these infections in the past or not even know they have them. If you notice any unusual symptoms soon after starting HIV drugs for the first time, let your doctor know right away so you can be evaluated and, if necessary, treated.
Eron, J.J, et. al. (2000). A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: selection of thymidine analog regimen therapy (START II). AIDS, 14(11).1601-10.
Gallant, J.E, et. al. (1999). Stavudine in zidovudine (ZDV)-experienced compared with ZDV-naive patients. AIDS, 13(2). 225-9.
John, M., et. al. (2003). Randomized, controlled, 48-week study of switching stavudine and/or protease inhibitors to Combivir/abacavir to prevent or reverse lipoatrophy in HIV-infected patients. Journal of Acquired Immune Deficiency Syndromes, 33(1). 29-33.
Molina, J.M, et. al. (1999). The ALBI trial: a randomized controlled trial comparing stavudine plus didanosine with zidovudine plus lamivudine and a regimen alternating both combinations in previously untreated patients infected with human immunodeficiency virus. Journal of Infectious Diseases, 180(2). 351-358.