Detailed information

Ritonavir  is a protease inhibitor, an anti-HIV drug that reduces the amount of virus in the body. Anti-HIV drugs such as ritonavir slow down or prevent damage to the immune system, and reduce the risk of developing AIDS-related illnesses. Protease (or proteinase) is the enzyme that HIV uses to break up large viral proteins from which new HIV particles can be made.

Ritonavir was approved for use in combination with nucleoside reverse transcriptase inhibitors (NRTIs) for treating adults with advanced or progressing HIV disease in Europe and the United States in late 1996.

Ritonavir was first manufactured by AbbVie, under the trade name Norvir. During early trials it was known as ABT-538 and A-84,538. Generic versions of ritonavir are available.

Although it was originally developed for use as a protease inhibitor in a three-drug combination, today ritonavir is used in low doses to boost the effect (blood levels) of one of the other protease inhibitors.


Ritonavir reduces HIV viral load and increase CD4 cell counts in the majority of people taking it in combination with at least two other antiretroviral drugs.

Ritonavir was approved after two main studies demonstrating its effectiveness in reducing AIDS-defining events and viral loads when added to an existing NRTI regimen (Study 247), and in reducing viral loads in treatment-naive patients (Study 245). (Cameron)

Subsequent studies found that ritonavir-based HIV treatment was as effective as treatment based on indinavir (Crixivan) in patients with prior exposure to NRTIs. After over a year of treatment, similar numbers of patients taking each drug developed a new AIDS-defining condition or died, and CD4 cell count increases were similar. (Floridia)

Ritonavir was soon replaced as a third agent in antiretroviral regimens by other protease inhibitors, as its side effects made ritonavir difficult to tolerate at a dose of 600mg twice daily.

Nowadays, low-dose ritonavir is used as a boosting agent to increase blood levels of other protease inhibitors. Ritonavir inhibits the activity of the gut and liver enzymes that break down protease inhibitors and clear them from the body. Taking a low dose of ritonavir alongside another protease inhibitor therefore increases the concentration of the other protease inhibitor in the blood and maintains it at effective levels in the blood for longer. (Cooper)

The boosting effect of ritonavir has been investigated in clinical trials of other protease inhibitors. See atazanavir, darunavir and lopinavir/ritonavir for details of studies of drugs in current use.

Taking it

Ritonavir is available in 100mg tablets, in a liquid formulation (80mg/ml) or as a powder to be dissolved in liquid.

In adults, low-dose ritonavir can be used with other protease inhibitors at the following doses: 

  • Atazanavir: 300mg with 100mg ritonavir once a day.
  • Darunavir: 600mg with 100mg ritonavir twice a day.
  • Lopinavir is only approved for use in combination with ritonavir and is only available in a fixed-dose combination with ritonavir. The standard dose is 400mg lopinavir with 100mg ritonavir twice a day.

See atazanavir, darunavir and lopinavir/ritonavir for further details.

Side effects

At full dose (no longer the way the drug is usually taken), the common side effects of ritonavir are: hives (itchy rash), acne, facial swelling, pins and needles, changes in sense of taste, peripheral neuropathy (nerve damage), headache, dizziness, difficulty in sleeping, anxiety, confusion, fainting, disturbance in attention, seizure, blurred vision, high blood pressure, coldness in the limbs, sore throat, cough, abdominal pain, nausea, diarrhoea, gastrointestinal bleeding, vomiting, indigestion, gastric reflux, loss of appetite, flatulence, mouth ulcers, pancreatitis, jaundice, frequent urination, heavy menstrual bleeding, tiredness, weakness, hot flushes, fever and weight loss.



An enzyme that HIV uses to break up large proteins into smaller ones from which new HIV particles can be made.


An essential organ involved in digestion of food and excretion of waste products from the body.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.


How well something works (in real life conditions). See also 'efficacy'.


A single change in gene sequence. Some HIV mutations cause the virus to become resistant to certain antiretroviral (ARV) drugs.

Lowered white or red blood cell count, low platelet count, raised cholesterol and triglyceride levels, raised liver enzymes or bilirubin, reduced kidney function, increased amylase and reduced thyroxine (thyroid hormone) are common laboratory side effects at full dose.

When used as a boosting agent, disturbances in taste and gastrointestinal side effects are the main side effects of ritonavir. (Cooper) Low-dose ritonavir has been shown to increase lipid levels in healthy volunteers. (Shafran)

While liver toxicity is a side effect of full-dose ritonavir, low-dose ritonavir does not increase the risk of liver toxicity, even in patients with hepatitis C co-infection. (Sulkowski) (Cooper)

Low-dose ritonavir may cause elevations of uric acid in the blood, which may lead to gout, particularly in patients with other risk factors. (Creighton)


Use of ritonavir at a low dose has not been shown to lead to ritonavir resistance. However, previous studies have found that mutations in the protease gene at codons 82 and 84 are associated with resistance to ritonavir, as well as mutations M46I/L, I50V, I54V and L90M. The I84V mutation reduces susceptibility to all available protease inhibitors, whereas V82A/T/F/S reduces susceptibility to indinavir and lopinavir.

Drug interactions

Because it inhibits the P450 liver enzymes, ritonavir interacts with a large number of other medicines. (Kempf) Some of these drug interactions may be life-threatening.

It is extremely important for patients taking ritonavir to check with their doctor before taking any other medications whatsoever.

The following drugs should be avoided or used with caution:

  • Abemaciclib (avoid unless essential)
  • Afatinib
  • Alfuzosin (avoid use)
  • Amiodarone (avoid use)
  • Amitryptiline
  • Amlodipine
  • Apalutamide (avoid use)
  • Astemizole (avoid use)
  • Atovaquone
  • Avanafil (do not use as treatment for pulmonary arterial hypertension, reduce dose when used as treatment for erectile dysfunction)
  • Bepridil (avoid use)
  • Bosentan
  • Budenoside
  • Buspirone
  • Carbamazepine
  • Cisapride (avoid use)
  • Ceritinib
  • Clarithromycin (avoid doses above 1g per day)
  • Clorazepate (avoid use)
  • Clozapine (avoid use)
  • Colchicine (use with caution in people with impaired liver or kidney function)
  • Cyclosporine
  • Dasitinib
  • Delaminid (do not use unless essential)
  • Dexamethasone
  • Diazepam (avoid use)
  • Dihydroergotamine (avoid use)
  • Diltiazem
  • Divalproex
  • Dronedarone (avoid use)
  • Encainide (avoid use)
  • Encorafenib (avoid use unless essential)
  • Ergonovine (avoid use)
  • Ergotamine (avoid use)
  • Erithromycin
  • Estazolam (avoid use)
  • Everolimus
  • Fexofenadine
  • Flecainide (avoid use)
  • Flurazepam (avoid use)
  • Fluticasone
  • Fostamatinib
  • Fusidic Acid
  • Glecaprevir / pibrentasvir (avoid use)
  • Haloperidol
  • Ibrutinib (avoid unless essential)
  • Itraconazole
  • Ketoconazole (reduce dose)
  • Lamotrigine
  • Levothyroxine
  • Lomitapide (avoid use)
  • Loratadine
  • Lovastatin (avoid use)
  • Lurasidone (avoid use)
  • Methylergonovine (avoid use)
  • Midazolam (oral) (avoid use)
  • Midazolam (parenteral) (use in intensive care unit only)
  • Neratinib (avoid use)
  • Nifedipine
  • Nilotinib
  • Pethidine (avoid use)
  • Phenytoin
  • Pimozide (avoid use)
  • Piroxicam (avoid use)
  • Prednisolone
  • Propafenone (avoid use)
  • Propoxyphene (avoid use)
  • Quetiapine (avoid use)
  • Quinidine (avoid use)
  • Ranolazine (avoid use)
  • Rifabutin (reduce dose to 150mg three times a week)
  • Riociguat (avoid use)
  • Risperidone
  • Rivaroxaban (avoid use)
  • Salemeterol (avoid use)
  • Sildenafil (do not use as treatment for pulmonary arterial hypertension, reduce dose when used as treatment for erectile dysfunction)
  • Simvastatin (avoid use)
  • St John's wort
  • Tacrolimus
  • Tadalfil (do not use as treatment for pulmonary arterial hypertension, reduce dose when used as treatment for erectile dysfunction)
  • Trazodone
  • Triamcinolone
  • Triazolam (avoid use)
  • Thioridazine
  • Vardenafil (avoid use)
  • Venetoclax
  • Vinblastine
  • Vincristine
  • Vorapaxar (avoid use)
  • Voriconazole (avoid use)
  • Warfarin

Co-administration of ritonavir with efavirenz  can increase the likelihood of side effects such as dizziness, nausea and unusual skin sensations, as well as elevated liver enzymes.

When ritonavir is used as a boosting agent, consult the drug interactions for the other protease inhibitor.

Ritonavir decreases the blood concentrations of the oral contraceptive ethinylestradiol, so alternative forms of contraception should be used.


Ritonavir is approved for use in children aged two years and over. See atazanavir, darunavir and lopinavir/ritonavir for details of the use of ritonavir-boosted protease inhibitors in children.

The liquid formulation of ritonavir is bitter. If children cannot stand the taste, it can be disguised by being given after peanut butter and followed with chocolate sauce or cheese. Alternatively, it can be mixed into chocolate milk.


See atazanavir, darunavir and lopinavir/ritonavir for details of the use of ritonavir-boosted protease inhibitors in pregnancy.


Cameron B et al. Randomised placebo-controlled trial of ritonavir in advanced HIV-1 disease. The Advanced HIV Disease Ritonavir Study Group. The Lancet, 351: 543-549, 1998.

Floridia M et al. A randomized trial comparing the introduction of ritonavir or indinavir in 1251 nucleoside-experienced patients with advanced HIV infection. AIDS Research and Human Retroviruses, 16: 1809-1820, 2000.

Cooper CL et al. A review of low-dose ritonavir in protease inhibitor combination therapy. Clinical Infectious Diseases, 36: 1585-92, 2003.

Shafran SD et al. The effect of low-dose ritonavir monotherapy on fasting serum lipid concentrations. HIV Medicine, 6: 421-425, 2005. You can read more about this study in our news report.

Sulkowski MS et al. Hepatotoxicity associated with protease inhibitor-based antiretroviral regimens with or without concurrent ritonavir. AIDS, 18: 2277-2284, 2004. You can read more about this study in our news report.

Creighton S et al. Is ritonavir boosting associated with gout? International Journal of STD & AIDS, 16: 362-364, 2005.

Kempf D et al. Coadministration with ritonavir enhances the plasma levels of HIV protease inhibitors by inhibition of cytochrome P450. Third Conference on Retroviruses and Opportunistic Infections, Washington, abstract 143, 1996.

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