Most protease inhibitors are prescribed with another drug (also a protease inhibitor) called ritonavir or an alternative boosting agent cobicistat. These drugs are both used to boost the effects of the protease inhibitor in your body. Without these boosters, your body would metabolise (break down) the protease inhibitor too quickly and it would not work effectively against the virus.

Protease inhibitors, including ritonavir, have multiple drug interactions. Most of these are caused by the boosting effect of ritonavir or cobicistat, which increase the levels of many drugs, including other protease inhibitors.

Do not take any protease inhibitors with the following medication:

• drugs for certain heart conditions, such as amiodarone, astemizole, flecainide, lercanidipine, quinidine and dabigatran
• alfuzosin (used to treat urinary problems)
• the anti-TB drug rifampicin
• the lipid-lowering drug simvastatin. Other statins such as rosuvastatin and atorvastatin can be used, but at lower doses
• the anticoagulant (a drug that prevents blood clotting) rivaroxaban
• midazolam, a benzodiazepine used as an anaesthetic. Midazolam can be used at reduced dose when injected as a sedative for certain procedures
• erectile dysfunction drugs, such as sildenafil (Viagra), tadalafil (Cialis) or vardenafil (Levitra) used at full dose. Get advice from your HIV doctor or pharmacist before taking any drugs for erectile dysfunction
• ergot derivatives (used to treat cluster headaches and migraines and to manage labour)
• antimalarial medications
• St John’s wort, the herbal antidepressant.

Some drugs can interact with protease inhibitors and change blood levels of one or both drugs, so dose adjustments with careful monitoring may be needed. This is the case for:

• calcium channel blockers (for example, diltiazem and verapamil)
• the heart drug digoxin
• the anticoagulant warfarin
• the asthma and allergy drugs fluticasone, salmeterol, budesonide, mometasone (including inhalers or nasal sprays)
• dexamethasone eye drops
• some steroid creams, especially if applied to large areas of skin
• treatments for acid reflux and ulcers called proton pump inhibitors and H2 receptor antagonists
• indigestion remedies
• some anti-fungal treatments (although not shampoos)
• anticonvulsants (drugs used to treat epilepsy; for example, phenytoin, carbamazepine). Some anticonvulsants should never be used with some PIs (see individual entries)
• the anti-TB drugs rifabutin and rifapentine
• immunosuppressants
• injectable steroids such as triamcinolone (Kenalog)
• some chemotherapy drugs.

Methadone levels may be reduced by protease inhibitors, and require an increase in dose to achieve the same effect.

Protease inhibitors may reduce the effectiveness of some hormonal contraceptives (such as the pill, patches or an implant). If you are using this type of contraceptive to prevent pregnancy you may need to use an additional or different type of contraception.

Names: Atazanavir, ATZ, Reyataz, and also available as a generic product. Also available as Evotaz, containing the boosting agent cobicistat.

Approved dosage: One 300mg capsule together with one 100mg ritonavir tablet taken together once a day. Evotaz: one pink combination tablet containing 300mg of atazanavir and 150mg of cobicistat once a day. Atazanavir is also available as a generic so its appearance will depend on which type your clinic dispenses.

Tips on taking it: Take once daily with food to improve absorption.

Common side-effects: (Atazanavir) Nausea, diarrhoea, rash, abdominal pain, headache, vomiting, heartburn, tiredness, raised bilirubin levels, sometimes leading to jaundice. (Evotaz) Increased appetite, difficulty in sleeping, abnormal dreams, headache, dizziness, altered taste, raised bilirubin levels, sometimes leading to jaundice, nausea, vomiting, diarrhoea, indigestion, abdominal pain, bloating, flatulence, dry mouth, rash, tiredness.

Developing some yellowing of the skin and/or eyes (jaundice) is fairly common, especially when you first start the drug. Although this can look alarming, it is harmless and does not mean that your liver is damaged, or not working in any way.

Rare side-effects: Kidney stones, severe rash and fever, changes in heart rhythm.

Children: Reyataz is approved for use in children aged 6 years and over. Powder also available for infants over 3 months.

Key drug interactions: See the start of this section on protease inhibitors for more information on possible interactions.

Drugs that affect the acidity of your stomach and gastrointestinal tract can stop atazanavir being absorbed, meaning it may not be effective at suppressing the virus:

• Proton pump inhibitors (indigestion remedies that reduce gastric acid, such as lansoprazole, pantoprazole or omeprazole) should not be taken with atazanavir, unless they have been prescribed by your HIV doctor and the dose of atazanavir is increased.
• H2 blockers (treatments for ulcers, such as ranitidine (Zantac)) should be taken only once a day, 4 to 12 hours after atazanavir (Reyataz). Evotaz should be taken with food at the same time as, or 10 hours after, anH2-receptor antagonist. If atazanavir is taken with tenofovir, you should never take H2-receptor antagonists without speaking to your doctor or pharmacist first.
• Indigestion remedies or calcium supplements should be taken at least two hours before or one hour after atazanavir.
• ‘Buffered’ medicines (drugs that have been prepared so they are released slowly into the body) should be taken at least two hours before or one hour after atazanavir.

Talk to your HIV doctor or pharmacist before taking any of these drugs with atazanavir, even if you only take them occasionally.

Atazanavir should not be taken with the anti-HIV drug nevirapine or the chemotherapy drug irinotecan.

Taking NNRTI drugs with atazanavir is not recommended.

Names: Darunavir, DRV, Prezista (also Rezolsta)

Approved dosage: Darunavir is available as a generic drug, so its appearance will depend on which type your clinic dispenses.

One 800mg tablet together with one 100mg ritonavir tablet taken together once a day. For more resistant HIV, your doctor may prescribe one 600mg tablet together with one 100mg ritonavir tablet taken together twice a day. Alternatively, you may be prescribed darunavir boosted by cobicistat (Rezolsta) (a light pink-coloured combination tablet containing 800mg of darunavir and 150mg of cobicistat once a day) if you do not have drug resistance. See also Symtuza in Single-tablet regimens.

Tips on taking it: Must be taken once or twice daily with food to improve absorption.

Common side-effects: Diarrhoea, vomiting, nausea, indigestion, rash, itching, abdominal pain, bloating, flatulence, headache, fever, peripheral neuropathy (damage to nerves in the hands or feet), lipodystrophy, difficulty in sleeping, weakness, tiredness, diabetes, raised creatine or amylase or triglyceride or cholesterol or liver enzyme levels. (Peripheral neuropathy, lipodystrophy and weakness are not common side-effects of Rezolsta or Symtuza.)

Rare side-effects: Abnormal liver function, changes in heart rhythm. 

Resistance: The drug works well in many people with resistance to other protease inhibitors.

Children: Approved for use in children. Prezista oral solution or reduced dose tablets available.

Key drug interactions: See the start of this section on protease inhibitors for more information on possible interactions.

The lipid-lowering drug pravastatin should be taken with caution with darunavir.

Names: Lopinavir/ritonavir, LOP, Kaletra.

Lopinavir is only available in combination with ritonavir.

Approved dosage:400mg lopinavir plus 100mg ritonavir twice a day, in yellow tablets containing 200mg lopinavir and 50mg ritonavir; two tablets are taken twice daily. Once-daily dose of four yellow tablets each containing 200mg of lopinavir and 50mg ritonavir is also available for people starting treatment for the first time.

Tips on taking it: The tablet can be taken with or without food, but must not be broken, chewed or crushed. Taking the doses with food can reduce potential irritation of the stomach.

Common side-effects: Nausea, vomiting, diarrhoea, abdominal pain, bloating, flatulence, tiredness, weakness, headache, heartburn and indigestion, pancreatitis, raised lipids or blood sugar, diabetes, high blood pressure, raised liver enzymes, cough, sore throat, runny nose, sinus infections, skin infections, rash, itching, allergic swelling, peripheral nerve damage, difficulty in sleeping, dizziness, muscle pain, erectile dysfunction, menstrual disorders.

Rare side-effects: Changes in heart rhythm, reduced kidney function.

Resistance: High-level resistance to other protease inhibitors may reduce the effectiveness of lopinavir/ritonavir.

Children: A Kaletra tablet containing 100mg of lopinavir and 25mg of ritonavir is available for use by children who can swallow a tablet. A liquid formulation is also available.

Key drug interactions: See the start of this section on protease inhibitors for more information on possible interactions.

Efavirenz and nevirapine reduce levels of Kaletra and dose adjustments are sometimes recommended when taking twice-daily Kaletra.

Once-daily Kaletra should not be taken with carbamazepine, phenobarbital or phenytoin (used to treat epilepsy).

Do not take Kaletra with fentanyl (for pain relief); trazodone; Zyban; or anti-cancer drugs called tyrosine kinase inhibitors.