Anti-HIV Drug Interactions

A Guide to the Interactions Found Between Anti-HIV Drugs and Common HIV-Related Therapies


With the number of drugs available to treat HIV and with those that prevent or treat opportunistic infections (OIs), the potential for drug interactions increases. Developing a health management plan and deciding which therapies to include in that plan may seem a daunting task. Not only does each therapy have possible side effects, but each might increase or decrease the benefit of the other drugs you take.

Talking to Your Doctor About Drug Interactions

Is it the medications that I am taking that make me feel sick ... Or is it the symptoms of the disease?Many people take a variety of therapies at the same time. These can range from experimental and approved anti-HIV drugs to complimentary and over-the-counter medicines. Drug interactions may play a major role in the success of any treatment plan. Unfortunately, they’re not always considered when developing a treatment strategy. The following are some suggestions to help prevent drug interactions:

  • Brown bag medicine checkup. Each time you see your healthcare provider, put all your meds -- including over-the-counter and complimentary products -- in a bag. Take the bag with you and have your doctor review those medicines for safety, appropriateness, compatibility and instructions for use.
  • New prescriptions. Each time your doctor prescribes you a new medication, ask him or her if it can be combined safely with your other therapies.
  • Regular discussion. Talk to your doctor about making the medicine checkup part of your regular visits. Discuss how best to check for possible drug interactions. (Bring Project Inform's publication, Drug Interactions, with you to your appointment.)

Drug interactions can take various forms, occurring immediately or over several weeks. Some drugs simply should not be used together, while others can be combined only if done with careful monitoring to detect emergency problems. Interactions can also occur when one therapy alters the effect of another. This includes how the other is absorbed in the body, broken down (metabolized), distributed or excreted.

A common interaction can occur when two drugs have similar side effect profiles. For example, both ddI and ddC can cause a tingling or pain in the legs, hands or feet (peripheral neuropathy). It’s not recommended that they be used together because the similar side effects may increase the potential for neuropathy. Similarly, AZT and ganciclovir (a treatment for CMV) may both cause bone marrow suppression, resulting in anemia. However, adding a third drug, G-CSF (Neupogen), can help manage this interaction. In addition, higher blood levels of a drug increase the chance of more side effects.

Patient: I started taking Aspirin for the pain recently. Doctor: I'm glad you told me about the meds you're taking.As it has become standard medical practice to prevent multiple OIs with different drugs, drug interactions become more of a concern. In some prevention regimens, drug interactions may even cause more harm than good. For example, one drug might reduce the blood levels of another drug, leading to drug resistance. This could result in a particular disease (like HIV or hepatitis) becoming unresponsive to treatment. The added toxicity of many therapies taken together may also outweigh their hopeful benefit for preventing disease. Therefore, healthcare providers and people with HIV should make informed decisions about combining therapies and OI prevention regimens and should carefully check for drug interactions and other side effects.

Unfortunately, most drug interaction studies have compared only two drugs, although most people with HIV often take many more than two. As a result, very little is known about how all the commonly used drugs interact with each other.

In the meantime, it's important to discuss possible drug interactions with your doctor and pharmacist. Before starting a new therapy (experimental, approved or complimentary), consider the possible drug interactions and side effects. Not everyone experiences side effects; and many drug interactions can be managed by monitoring carefully, adjusting the doses, or stopping the therapy as needed.

The following chart should only be used as a guide for possible drug interactions. Remember that these interactions might occur in some people, but not in others. This chart was put together with information from prescription package inserts, anecdotal reports, discussions with pharmacologists and doctors who treat HIV disease, and discussions with drug companies.

Drug List

Anti-HIV Medications + Street Drugs: Some Cocktails Don't Mix

Reprinted from Notes from the Underground, Winter 1998-99, #38

For most drugs to be effective and not kill you, they need to be metabolized [broken down] by the liver or kidneys. These organs have limited resources and a set number of chemicals which accomplish this task. Because of this, certain drugs, whether they're HIV medications or recreational drugs, can affect how other drugs act. This is called a drug interaction -- and some of them can be deadly.

There hasn't been much research on how street drugs and HIV medications interact -- because there is little financial incentive for the pharmaceutical companies to do the work, and because the government believes "just say no," is the only way to deal with drugs. Certainly, your best bet is not to take street drugs at all if you are taking HIV medications. Bus some interactions are deadlier than others.

Ecstasy (X, MDMA)

There has already been one death in England which resulted from a regular dose of ecstasy (MDMA, X) taken with ritonavir. Ritonavir acts to slow down the liver enzyme that breaks down X -- so it makes the dose 5-10 times stronger. In addition, between 3-10% of the white population (the figure for other populations is not known) have a deficiency in this enzyme, which may be why some people overdose on what may be a safe dose for others. If you are taking any protease inhibitor [ritonavir, nelfinavir, indinavir, saquinavir (Fortovase)] or NNRTI [nevirapine delavirdine or efavirenz], X can be extremely dangerous. Of these, ritonavir and delavirdine seem to be the most dangerous, while nevirapine and efavirenz may be less so -- although because effects in the test tube have sometimes been opposite to those seen in the body, this is hard to predict.

If you do take X with a protease inhibitor, wait as long as possible after taking the protease inhibitor to take the X, and be sure to have someone with you who knows what you've done in case you have difficulties. These overdoses are often not reversible, so it's really better not to mix these drugs!

Recent research has found that X damages serotonin neurons, so avoid it if you have a family or personal history of depression or anxiety disorders.


ddI can increase the risk of pancreatitis (intense stomach pain that feels like it's going all the way through to your back. So, if you're using alcohol regularly, don't use ddI. There are other nucleosides to choose from.

Occasional and light use of alcohol is not known to interact with other HIV medications; however, chronic, heavy use can be destructive to the liver. This can be dangerous because the way drugs are broken down can be hurt. More drugs will stay in your system for the most part, which is likely to cause overdoses and worse side effects. Alcohol can cause dehydration; so be sure to drink lots of water to help your body deal with any alcohol you drink.


Protease inhibitors may increase THC levels (the active ingredient in marijuana) -- so smaller doses may make you more stoned. This is also true of the synthetic version (Marinol) used in the treatment of weight loss. Since THC overdose is impossible, this interaction is not dangerous.


The sedatives Halcion (triazolam), Valium (diazepam), Ambien (zolpidem) and Versed (midazolam) can also be deadly if mixed with protease inhibitors. Norvir has the largest negative effect. At high doses these drugs can stop your breathing. Ativan (lorazepam), Serax (oxazepam) and Restoril (temazepam) are safer with Norvir, and may actually be weakened by it.


Crixivan may increase blood levels of phenobarbital (Luminal), making overdose more likely. Other protease inhibitor interactions are also possible.

Cocaine (coke, blow)

There are no known interactions between cocaine and HIV medications, but in the test tube, cocaine doubles the speed at which the virus reproduces, meaning it may speed up how sick you get.

Heroin (smack, brown, junk, China White)

Ritonavir seems to reduce heroin levels by 50% making overdose less likely. However, this drug and the other protease inhibitors have sometimes been known to have opposite effects (they cut methadone levels in real life, while test tube experiments predicted they would increase them), so caution is in order. Some synthetics sold as heroin (fentanyl, alpha-methyl-fentanyl) are potent in tiny doses and could be deadly if mixed with another drug.

GHB (gamma-hydroxy-butyrate, grievous bodily harm, liquid X)

GHB is potentially dangerous with Norvir and other protease inhibitors.

Amyl nitrite (amyl nitrate/poppers)

Glutathione is used by the liver to process amyl nitrite, and high glutathione is linked with survival. If using amyl nitrite cuts glutathione, it could lead to disease progression.

LSD (acid)

No known interactions.

Ketamine (Special K)

When combined with ritonavir, special K can lead to "chemical hepatitis," an unpleasant inflammation of the liver resulting in jaundice. A New York HIV doctor has seen two cases of it. Both went away in several weeks. But anything which damages the liver can be a serious problem for people living with HIV.

Amphetamines (dexedrine, amphetamine, methamphetamine, crystal meth)

Ritonavir is predicted to increase amphetamine levels in the blood by a factor of 2-3. The other protease inhibitors should have less of an impact, but strange opposite results are always possible.


Norvir and other similar drugs can either strengthen Ritalin's effects or make it weaker.


Interactions not listed could be deadly. Street drugs are often not what they are sold as, they are frequently cut with substances that may interact with drugs themselves and their potency can vary wildly, even in the same batch. With the lack of research in this area, it's better to avoid potential interactions if at all possible.