The body metabolizes (breaks down) the drugs you take. This process involves the liver and kidneys:

• Proteins in the liver called enzymes break down the drug
• The kidneys remove the drug from the bloodstream
• The drug is eliminated from the body in urine or feces

Sometimes, one drug affects the way another drug is metabolized. This is called an interaction. Some interactions do not cause problems and may even be beneficial. However, some interactions decrease a drug’s effectiveness and increase side effects.

Potential drug interactions should be taken into consideration when selecting a new HIV regimen or when any new drug is added to an existing regimen.

Some drugs inhibit (slow down) the action of the liver enzymes. This causes other drugs to be metabolized and eliminated from the system more slowly, which:

• Increases the amount of other drugs in the body
• Increases the length of time other drugs stay in the bloodstream

This can be useful in HIV therapy. For example, the protease inhibitor (PI) Norvir (ritonavir) significantly slows down the liver enzymes. Low doses of Norvir are often used to increase or “boost” the concentration of other PIs. This can make the other PI work so much better that you can take fewer doses and fewer pills.

Unfortunately, increased blood levels of drugs can also cause overdoses or increased side effects. If you are taking a drug that slows down liver enzymes, your doctor may need to adjust the doses of your other medications.

Some drugs induce (speed up) the action of the liver enzymes. This causes other drugs to be metabolized and flushed out of the system more rapidly, which:

• Decreases the amount of other drugs in the body
• May cause other drugs to be less effective

Some drugs used to treat HIV-related conditions speed up the liver enzymes. This can be a serious problem if it causes the HIV drugs to be metabolized too quickly. If HIV drug levels drop too low:

• HIV can multiply
• Viral load can go up
• Resistance can develop
• HIV drugs can stop working

If you are taking a drug that speeds up liver enzymes, your doctor may need to increase the doses of your other medications.

If drugs cause similar side effects, combining them may increase the amount or seriousness of those side effects. For example, combining d4T (Zerit) with ddI (Videx) may increase the risk of lactic acidosis (high levels of lactic acid in the blood), especially in pregnant women. HIV+ pregnant women should not take d4T and ddI together.

Some drugs work against each other and should not be taken together. An example is AZT (Retrovir) and d4T (Zerit).

There is a long list of drugs that may have significant interactions with HIV medications. Below are a few examples:

Birth control pills containing ethinyl estradiol can interact with HIV drugs. This can make the pills less effective and increase the chances of pregnancy. If your HIV drugs affect the levels of your birth control pills, you should switch to another form of birth control.

Levels of the PI Agenerase are decreased by birth control pills, which can put you at risk for drug resistance. For this reason Agenerase is not recommended for use with birth control pills.

Many HIV+ people use complementary therapies such as vitamins or herbs. While most of these have not been studied with HIV drugs, St. John’s Wort (an herbal anti-depressant) and garlic supplements have been shown to decrease levels of PIs. Make sure to tell your doctor if you take any complementary therapies. 

There have been reports of overdoses, some fatal, caused by taking recreational drugs and HIV drugs. Interactions between ecstasy or amphetamines (crystal meth, speed) and PIs are particularly dangerous.

Alcohol affects body processes and is often responsible for drug interactions. Combining alcohol and certain HIV drugs like ddI can put you at risk for developing pancreatitis (inflammation of the pancreas).

Methadone can interact with many HIV drugs. Tell the doctor at the methadone program and your HIV doctor what you are taking. This way necessary adjustments can be made to insure you get enough methadone to prevent withdrawal symptoms and enough HIV drugs to fight the virus effectively.

What you eat can affect how much of your drugs get into your system. Certain drugs need to be taken on an empty stomach and others work better with food. Check your drug labels and follow the food instructions carefully.

If you are having problems with side effects or drugs not working well, it may be helpful to have your drug levels checked using a test called Therapeutic Drug Monitoring (TDM). If your levels are too high or too low, your doctor may adjust your doses or switch some of your medications. (At this point, TDM is not widely used in HIV treatment.)

HIV+ people often have to take many different drugs. To get the best results, it is a good idea to:

• Keep a list of all your drugs (including prescription, over-the-counter, vitamins, supplements, herbs, and recreational drugs) and ask your doctor to review it for possible interactions
• Give a copy of your drug list to all of your health care providers
• Discuss all your medical conditions with your doctor
• Each time you are prescribed a new medication, check with your doctor to see if it can be combined safely with your other therapies
• Have all your prescriptions filled at one pharmacy
• Learn about all the possible side effects of your drugs
• Learn how, when, and with what to take your drugs
• Don’t stop or change your drugs without talking to your doctor
• Report any side effects to your doctor

1		Falkner, B. & Kosel, B. (2003). Methadone and HIV medications: Drug interactions. Who needs to care? STEP Perspective, 2(3).
2		U.S. Department of Health and Human Services’ AIDSInfo (2003). Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents: Retrieved July 2003 from http://aidsinfo.nih.gov/guidelines/default_db2.asp?id=50.