What to Know About HIV Booster Drugs (Pharmacokinetic Enhancers)

How Norvir (Ritonavir) and Tybost (Cobicistat) Work

Pharmacokinetic enhancers are drugs used in the treatment of HIV that increase the concentration of other antiretroviral medications in the bloodstream. Popularly referred to as "boosters," the drugs allow healthcare providers to reduce the dose and frequency of the accompanying drug while lowering the risk of side effects and drug resistance.

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There are two pharmacokinetic enhancers approved for use by the Food and Drug Administration (FDA):

  • Norvir (ritonavir)
  • Tybost (cobicistat)

HIV booster drugs should not be confused with vitamins or supplements marketed as "immune boosters," which neither prevent nor treat HIV.


When a class of antiretroviral drugs called protease inhibitors (PIs) were first discovered in the mid-1990s, one of the main challenges was the rapid speed at which the drugs were metabolized and cleared from the bloodstream. As a result, PIs typically had to be taken two to three times a day to maintain a steady therapeutic blood concentration.

The problem with this, of course, is that it exposes people to high doses of the drug. This, in turn, increases the risk of PI-associated side effects, including hepatotoxicity (liver poisoning), lipodystrophy (abnormal body fat redistribution), and urolithiasis (the formation of kidney stones).

Moreover, it made the drugs far less "forgiving," meaning that drug resistance could develop if you had anything less than perfect drug adherence.

All of that changed in 1996 with the introduction of a drug called Norvir.

Norvir (Ritonavir)

Norvir (ritonavir) is classified as a protease inhibitor. While it was first prescribed for its antiviral properties, researchers soon discovered that, even at low doses, Norvir could block the very enzyme—called CYP3A4—used to metabolize PIs. By blocking this action, PIs become more durable (longer-lasting) and required lower doses to achieve the same effect.

The discovery immediately impacted the way in which PIs were prescribed. Today, Norvir is rarely used for its antiviral properties but rather to increase the efficacy of the accompanying PI.

Available in tablet, soft gel capsule, and liquid forms, Norvir is used in combination antiretroviral therapy to boost the concentration of any of the four FDA-approved HIV protease inhibitors.

The drug is also contained in the fixed-dose combination tablet Kaletra (lopinavir + ritonavir). Generic versions are also available under the chemical name "ritonavir."


Norvir is used to treat HIV as part of PI-based therapy. It can be used in adults and children older than 1 month of age. There are no off-label uses for the drug.

Before Taking

If you are newly diagnosed or changing treatment due to a treatment failure, your healthcare provider will order blood tests to determine which drug you are most sensitive to.

This includes genetic resistance testing to determine if you have any drug-resistant mutations that might exclude certain drugs, and phenotypic testing in which the virus is directly exposed to all antiretrovirals to see which ones work best. If a PI is selected based on these tests, it is always accompanied by a booster.

Norvir is contraindicated for use in people who have had a prior hypersensitive reaction to ritonavir.


Norvir is available as a 100-milligram (mg) tablet, a 100-mg soft gel capsule, and an 80-mg-per-milliliter (mg/mL) flavored syrup formulation. The Norvir dosage is always titrated (meaning started at a lower dosage and incrementally increased to full strength).

When used in children, the dosage is calculated based on the child's body surface area (mg per m2).

Group Recommended Dose Administration
Adults 600 mg twice daily with food Start at a minimum of 300 mg twice daily and increase by 100mg twice daily every two to three days, never exceeding 600 mg twice daily
Children 350 to 400 mg per m2 twice daily with food Start at a minimum of 250 mg twice daily and increase by 50 mg twice daily every two to three days, never exceeding 600 mg twice daily

Tybost (Cobicistat)

In 2014, a full 18 years after Norvir was first introduced, a second booster drug called Tybost (cobicistat) was formally approved by the FDA.

Tybost is a drug analog of ritonavir (meaning that it is chemically similar) but has been altered in such a way that it has no antiviral properties. As such, it is classified specifically as a CYP3A4 inhibitor.

Although Tybost is related to Norvir, by stripping the drug of its antiviral effect, it exerts no action on HIV and cannot cause cobicistat-resistant mutations.

Another way that Tybost differs is that can boost drugs other than PIs, most notably the integrase inhibitor elvitegravir. With that being said, Tybost is not interchangeable with Norvir.

Tybost is used solely in combination with the protease inhibitors Prezista (darunavir) or Reyataz (atazanavir) and is not used to boost either Aptivus (tipranavir) or Lexiva (fosamprenavir).

Cobicistat can also be found in the following fixed-dose combination drugs:

Tybost is available as an oral tablet. There are no generic versions of Tybost.


Tybost is used to treat HIV in adults 18 and over as part of combination antiretroviral therapy. There are no off-label uses for the drug.

Before Taking

As with Norvir, genetic resistance testing and occasionally phenotypic testing are performed prior to the start of any new treatment regimen.

Because Tybost can boost Viread (tenofovir disoproxil fumarate), an antiretroviral classified as a nucleoside reverse transcriptase inhibitor (NRTI), kidney function tests are routinely performed if the drugs are used together.

Viread is associated with an increased risk of kidney impairment, and the combined use may cause kidney failure in those with pre-existing kidney disease.

Tybost is not recommended in a tenofovir-based regimen for people who have a creatinine clearance (a measure of kidney function) of less than 70 milliliters per minute (mL/min).

Tybost should not be used by anyone who has had a prior hypersensitive reaction to cobicistat.


Tybost is manufactured as a 150-mg tablet. The recommended dosage varies by the accompanying PI as well as whether the person is newly treated (treatment-naive) or has been previously exposed to antiretroviral therapy (treatment-experienced).

Accompanying PI Recommended Dose Approved Use
Reyataz (atazanavir) 300 mg once daily Tybost 150 mg once daily taken with food Treatment-naive or treatment-experienced
Prezista (darunavir) 800 mg once daily Tybost 150 mg once daily taken with food Treatment-naive only

Side Effects

Although Norvir and Tybost share similar mechanisms of action, their side effects are far different. While most are tolerable and tend to resolve as your body adapts to treatment, some can be severe and require the immediate discontinuation of treatment.


Comparatively, Tybost has fewer side effects than Norvir, mainly because it exerts no direct antiviral action.

Tybost is also far less likely to cause side effects. While as many as 6% of Tybost users will report side effects, more than half of Norvir users will report gastrointestinal side effects while one in four will report a rash.

Common side effects, by order of frequency, include:

  • Diarrhea

  • Nausea

  • Altered taste

  • Fatigue

  • Vomiting

  • Rash

  • Abdominal pain

  • Coughing

  • Joint pain

  • Dizziness

  • Flushing

  • Itchiness

  • Upset stomach

  • Peripheral neuropathy

  • Jaundice

  • Rash

  • Nausea

  • Diarrhea

  • Headache

Always advise your healthcare provider about any side effects you experience, particularly if they are persistent or worsening.


Tybost is also less likely to cause severe side effects than Norvir. There are many reasons for this, but, among them, Tybost doesn't cause mitochondrial toxicity as Norvir can. Mitochondria are the energy units within cells. Damage to them can affect normal metabolism and trigger an array of adverse effects.

Although severe side effects are uncommon, people with certain pre-existing conditions (like liver disease or obesity) may be at a bigger risk. Possible complications include:


Warnings and Interactions

As both Norvir and Tybost inhibit the CYP3A4 enzyme, they are often avoided with other drugs that rely upon CYP3A4 for metabolism. The competition for the enzyme can alter the concentration of the booster drug and/or accompanying drug in the bloodstream. Reduced concentrations lower the effectiveness of the drugs, while increased concentrations increase the risk of drug toxicity.

Norvir carries a black box warning from the FDA advising consumers that the drug can boost certain classes of drugs to dangerous and potentially life-threatening levels, including sedatives, antiarrhythmics, or ergot alkaloids.

Advise your healthcare provider if you take any of the following and are prescribed Norvir or Tybost:

  • Altoprev (lovastatin)
  • Antabuse (disulfiram)
  • Demerol (meperidine)
  • Dilantin (phenytoin)
  • Halcion (triazolam)
  • Inspra (eplerenone)
  • Mellaril (thioridazine)
  • Orap (pimozide)
  • Pacerone (amiodarone)
  • Percocet (oxycodone)
  • Propulsid (cisapride)
  • Ranexa (ranolazine)
  • St. John's wort
  • Serevent (salmeterol)
  • Sular (nisoldipine)
  • Tambocor (flecainide)
  • Tasigna (nilotinib)
  • Tegretol (carbamazepine)
  • Tracleer (bosentan)
  • Versed (midazolam)
  • Vfend (voriconazole)
  • Zocor (simvastatin)

To avoid interactions, always tell your healthcare provider about any drugs you take, whether they are prescription, over-the-counter, herbal, or recreational.

Norvir and Tybost are generally considered safe for use during pregnancy. Animal studies have shown no evidence of fetal harm, although well-controlled studies in humans are lacking. Always speak with your healthcare provider about the benefits and risks of treatment if you are pregnant, planning to conceive, or of child-bearing age.

8 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. Abbvie. Package insert - Norvir.

  3. Gilead Sciences. Package insert - Tybost.

  4. National Institute of Diabetes and Digestive and Kidney Diseases. Protease inhibitors (HIV). In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

  5. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Laboratory testing for initial assessment and monitoring of patients with HIV receiving antiretroviral therapy.

  6. Greenblatt D. Antiretroviral boosting by cobicistat, a structural analog of ritonavir. Clin Pharmacol Drug Dev. 2014 Sep;3(5):335-7. doi:10.1002/cpdd.159

  7. Deeks ED. Cobicistat: A review of its use as a pharmacokinetic enhancer of atazanavir and darunavir in patients with HIV-1 infection. Drugs. 2014 Feb;74(2):195-206. doi:10.1007/s40265-013-0160-x

  8. U.S. Department of Health and Human Services. FDA-approved HIV medications.

By James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.