HIV Drugs: ART Interactions

Medically Reviewed by Jonathan E. Kaplan, MD on March 05, 2022
6 min read

If you take antiretroviral therapy (ART) to manage HIV, it’s common for your HIV drugs to have interactions with other medicines you take.

Drug interactions are when medications taken together or close to the same time cause problems. One or all may not be as effective. Or the combination may cause you to have side effects.

There are many ways in which drug interactions can happen. Drug interactions with ART can range from unimportant to mild to serious. Before your doctor prescribes ART, they’ll consider all the drugs you take, for any reason, to be sure your ART doesn’t interact with them.

When you start any new drug, it’s always a good idea to make sure your doctor or a pharmacist looks over your list of drugs to check for interactions.

An enzyme called CYP3A plays an important role in how your body metabolizes, or absorbs and processes, your ART drugs. It also affects other drugs you may take. Some of these drugs could interfere with how CYP3A and other enzymes process your medications. This could either lessen or raise the amount of active ingredients in your treatments.

Two ART medicines called boosters or enhancers (cobicistat and ritonavir), make CYP3A less active. But they raise the levels of ART drugs in your system when they combine with them. Doctors give them with some other drugs called protease inhibitors (PIs). These include atazanavir (Anzavir, Evotaz), darunavir (Prezcobix, Symtuza), and lopinavir (Kaletra). They also use them with an integrase strand transfer inhibitor (INSTI), elvitegravir (Genvoya, Stribild). But they may also raise levels of other drugs that you take.

Some of the newer INSTIs (bictegravir, dolutegravir, and raltegravir) tend to have fewer drug interactions than other HIV drugs. This is one of the reasons that INSTIs are now preferred drugs for HIV treatment.

Of the many possible drug interactions, here are some important ones to know about if you’re on ART:



Doctors use direct oral anticoagulants (DOACs), or blood thinners, to stop clots that may cause heart attacks and strokes.

Possible interactions

The anticoagulants apixaban (Eliquis), dabigatran (Pradaxa), edoxaban (Savaysa), rivaroxaban (Xarelto), and warfarin (Coumadin) may interact with ART drugs boosted by cobicistat or ritonavir. They may also interact with some non-nucleoside reverse transcriptase inhibitors (NNRTIs).

What could happen?

Drugs boosted by cobicistat or ritonavir could make your body absorb too much anticoagulant and raise the chances that you’ll bleed. Some NNRTIs can lower the amount of anticoagulant your body takes in, so your blood thinners don’t work as well to stop or break up clots. If you take a blood thinner with some of these ART drugs, you’ll need to do so carefully with the supervision of your doctor or pharmacist.

Warfarin (Coumadin) may also interact with ART in ways you can’t predict. Taking warfarin with drugs boosted by cobicistat or ritonavir, or with some NNTRIs, may change the levels of warfarin in your blood. If you do take these drugs together, your doctor will keep a careful eye on your results.


Calcium Channel Blockers

Calcium channel blockers treat high blood pressure. They block calcium from your arteries or heart. This keeps your arteries more relaxed and open.

Possible interactions

Calcium channel blockers may interact with drugs boosted by cobicistat or ritonavir, and with some NNRTIs.

What could happen?

Drugs with cobicistat or ritonavir may raise the amount of calcium channel blocker you take in. You can use these drugs together, but your doctor may start you on a low dose of a calcium channel blocker. They might adjust your blood pressure medicine. They might also keep track of how you respond with regular electrocardiogram (EKG) tests.

If you take the PI atazanavir with or without cobicistat or ritonavir, your doctor may cut your dose of the calcium channel blocker diltiazem in half. This is because atazanavir can greatly increase the amount of diltiazem you absorb.

Some NNRTIs can lower the amount of calcium channel blocker your body can process. If you take these medications together, your doctor may carefully adjust your dose of calcium channel blocker until it can control your blood pressure.


Proton Pump Inhibitors

Proton pump inhibitors (PPIs) are drugs that cause your stomach to make less stomach acid. Doctors use them to treat acid reflux (GERD) and heartburn. These are common problems for people with HIV.

Possible interactions

The PI atazanavir and the NNRTI rilpivirine are the most likely ART drugs to have interactions with PPIs and other acid-control drugs.

What could happen?

Atazanavir and rilpivirine need an acidic stomach to dissolve so your body can use them easily. If the use of a PPI cuts down on your stomach acid, these drugs may not break down and get into your bloodstream well enough to control your HIV.

If you’ve been taking a PPI and need to start atazanavir, take the drugs at least 12 hours apart. Your PPI dose shouldn’t be higher than the equivalent of 20 milligrams of omeprazole. Don’t take a PPI with atazanavir that’s not combined with cobicistat or ritonavir. If you’ve been on ART and need to take a PPI, you should stay away from atazanavir.

If you take ART with darunavir combined with ritonavir, these drugs may interfere with omeprazole such that this PPI might not work for you. The same is true for tipranavir, which you should not take with omeprazole.

You shouldn’t take any PPI with rilpivirine. Doing this can lower the amount of rilpivirine that your body absorbs to the point where it doesn’t work well anymore.



High cholesterol is common if you have HIV. Statins are drugs that lower your cholesterol levels. They lower your risk of heart attacks and strokes. They also keep plaque in your blood vessels stable so they don’t form clots.

Doctors will often use statins to treat high cholesterol in people who are HIV-positive.

Some ART drugs raise cholesterol levels, so your doctor may switch you to a different ART if you develop high cholesterol instead of putting you on a statin.

Possible interactions

The most common interaction is when you take the statins atorvastatin, lovastatin, or simvastatin with ART that includes cobicistat, efavirenz, or ritonavir. But they’re also possible with some NNRTIs. Statins also cause side effects like muscle pain or weakness. These effects are linked to the amount of statin your body takes in.

What could happen?

You shouldn’t use lovastatin or simvastatin with any ART that contains a PI, whether the PI is combined with cobicistat or ritonavir or not. It can cause muscle weakness or kidney failure. Also, you shouldn’t use these drugs with elvitegravir (which is combined with cobicistat) because you’ll absorb too much statin.

If you take atorvastatin with ART that includes cobicistat or ritonavir, it could make you absorb too much of the statin. Your doctor will prescribe a lower dose, such as 20 milligrams a day or less, to start.

If you take atorvastatin, lovastatin, or simvastatin along with some NNRTIs, the NNRTIs may make your statin less effective at controlling your cholesterol.