Norvir, also known as ritonavir, is an HIV medication in the class called protease inhibitors (PIs) that works by preventing HIV from completing the final step in making new copies of itself after it infects the T cell. While it’s not the first PI approved by the U.S. Food and Drug Administration (FDA), Norvir—which has been around since 1996—is remarkable for both its longevity in the HIV treatment field and for its evolution over time.
The History of Norvir as an HIV Medication
Initial studies showed that Norvir—when combined with two nucleoside reverse transcriptase inhibitors (NRTIs) like AZT, D4T, 3TC, or others—was an effective HIV treatment regimen. In fact, a study of Norvir plus two NRTIs first reported in 1996 was among the first to demonstrate a significant survival benefit associated with the use of a protease inhibitor in combination with older HIV drugs.
In those days, there were no single-tablet regimens, so it was the norm to have regimens consisting of multiple medications that had to be taken two or three times daily. In 1996, when Norvir was first FDA-approved, the dosing was six 100-mg soft-gel capsules twice a day—that’s a total of 12 soft-gel capsules daily, taken with food—with a refrigeration requirement to maintain its integrity. It also came in an oral solution for both children and anyone who had trouble swallowing capsules, as well as a powder form. Over time, the pill formulation and dosing fell out of favor due to pill burden, refrigeration requirements, and side effects.
The Evolution of Norvir Into a Booster Drug
In the 2000s, scientists discovered that Norvir could be used at a much lower dose—as low 100 mg once daily—and paired with another PI as part of a complete antiretroviral therapy (ART) regimen. The reason behind this switch was the discovery that Norvir has the ability to block an enzyme in the liver that processes other protease inhibitors. By increasing and prolonging the levels of these other protease inhibitors in the body, it made them work better at suppressing HIV from making copies of itself.
This began the concept of “boosting” other protease inhibitors with Norvir, in which the drug was prescribed along with other PIs (like Prezista [darunavir] or Reyataz [atazanavir]) at a lower dose. Not only did this help the other medications work better, but it also reduced their dosing, which had additional benefits: Without Norvir “boosting,” Prezista and Reyataz needed to be taken twice a day. With boosting, they could be taken once a day, at least by people starting a protease inhibitor–based regimen for the first time. Using Norvir as a booster also required a much lower dose of Norvir, which reduced the frequency and severity of Norvir side effects experienced by people living with HIV.
One of the most famous and popular pairings of Norvir was with another PI named lopinavir, marketed together with Norvir under the brand name “Kaletra,” which was approved by the FDA in 2000. Kaletra was the first coformulation of two protease inhibitors into a single tablet.
Kaletra became one of the first truly durable “workhorses” in combination ART, demonstrating superiority to other PIs in suppressing viral loads to less than 50 copies/mL (i.e., making a person’s viral load undetectable), as well as showing a higher genetic barrier to resistance compared to other PIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs). As a result, Kaletra became one of the most popular PI-based regimens for providers and patients alike during the 2000s, and the standard of care by which other ART regimens were often measured.
Norvir has also been effectively paired with all the other PIs as a boosting medication, demonstrating both durability and effectiveness in sustained viral suppression among people living with HIV.
Norvir’s Changing Role in Treatment Regimens
In 2010, the FDA approved Norvir in a 100-mg tablet form that didn’t require refrigeration and made it much easier for people with busy lives to fit dosing into their schedules.
Nowadays, Norvir’s higher twice-a-day dosing is rarely (if ever) used. As a component of Kaletra and other “boosted” PI regimens, it had enjoyed status as part of a recommended initial combination ARV regimen for patients who are ARV-naive by the Department of Health and Human Services (DHHS) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV for many years. Over time, however, its utility as part of a boosted ART regimen has taken a back seat to the newer single-tablet regimens and other ART combinations that boast reduced pill burden, durable medications with higher genetic barriers to resistance, fewer side effects, and no need for an additional medication as a booster.
Additionally, with the emergence of cobicistat (Tybost) as an alternative HIV medication booster that offers a better side-effect profile, it is clear why Norvir has fallen out of favor as a preferred initial ART medication.
How to Take Norvir
Norvir is FDA-approved in the United States to be taken as part of ART in several ways.
- Twice a day with food when taken as a 600-mg soft-gel capsule.
- Twice a day as an oral solution at 80 mg/mL up to 600 mg with food.
- Boosted 100-mg tablet dosing with other PIs, either twice a day or once daily with or without food.
- Boosted 100-mg oral powder sachets in suspension, 600 mg twice daily with food.
The older, higher dosing of Norvir (capsules, powder, and liquid) is recommended to be taken with food for both absorption and reducing potential side effects. The lower boosted dose of 100 mg, when paired with other PIs, can be taken either with or without food.
How Much Does Norvir Cost in the U.S.?
The cost of Norvir can range from $278/month for the 100-mg powder or tablet formulation to $1,513/month for the oral liquid solution.
If you have insurance, monthly copays for Norvir can typically run between $50 and $100 depending on the plan, though you may qualify for cost-sharing assistance provided by the manufacturer.
If you don’t have insurance or your insurance won’t cover the majority of Norvir’s cost (you are “underinsured”), the [patient assistance program](https://www.abbvie.com/patients/patient-assistance/program-qualification/ orvir-program-selection.html) can also help reduce or eliminate the cost, depending on your financial situation.
The first generic version of Norvir, sold as ritonavir, became commercially available in the U.S. in early 2018. Today, several generic versions are available, and their average cost is significantly lower than that for brand-name Norvir.
Side Effects of Norvir
As with many ART regimens, there is the potential for mild side effects, particularly when first starting out on meds or switching to Norvir. Most often, the following mild symptoms may occur:
- Mild rash
- Upset stomach
A general rule of thumb is what we call “the two-week rule”—when starting your HIV treatment regimen, give your body about two weeks for it to get adjusted to the medication.
Sometimes rashes, mild fever, joint pain, or other symptoms may happen. This could be related to the medication working and your immune system getting stronger, which can manifest as these symptoms. Keep in touch with your medical team and let them know as you move forward.
If, after a couple of weeks, you are still having bothersome symptoms or they are getting worse, let someone from your medical team know so that you can schedule a virtual or in-person meeting to discuss.
In this day and age, we have varying options for HIV treatment, and even if a medication worked well for one of your friends, that doesn’t necessarily mean that your body will respond to it in the same way. Speak up, let your provider know, and discuss whether they feel labs are needed and/or recommend switching up your regimen altogether.
Other Potential Side Effects of Norvir Worth Noting
There are very rare concerns of buildup of lactic acid in the blood or liver problems, so pay attention to any new or worsening symptoms of fever, abdominal pain, nausea/vomiting, or unusual muscle aches.
Norvir has been found to increase cholesterol levels as well as contribute to fat buildup in the back of the neck and/or waistline (lipodystrophy), so watching for body or weight changes is important when on Norvir.
Side Effects of High-Dose (Older) Norvir
Perhaps the most striking side effects that have dogged Norvir from the early days of its use in the 1990s are the gastrointestinal ones. Symptoms like abdominal pain, cramping, nausea/vomiting, gas, and diarrhea are commonly noted among people who are on Norvir, particularly at the higher 600-mg, twice-a-day dosing schedule.
These side effects often discouraged adherence with Norvir if people were prescribed it by their clinicians and also fostered reluctance to even start it when recommended by providers.
Fortunately, there are more potent ART options today with fewer side effects, and patients often will comment on how much better they feel overall when switching off of an older Norvir-based regimen.
Interactions Between Norvir and Other Drugs
As a boosting medication, Norvir helps other PIs stay in the bloodstream longer, thereby making them more effective at keeping HIV virally suppressed. However, this also means it has the potential to interact with many other medications, when you consider that it blocks one of the proteins in the liver that helps process many common medications. This could cause their drug levels to increase in the body, increasing the potential for side effects.
Common medications likely to interact with Norvir include:
- Steroids like fluticasone (typically found in inhalers for asthma and COPD).
- Cholesterol medications like simvastatin.
- Blood-pressure medications like certain calcium-channel blockers and beta blockers.
- Some antidepressants.
- St. John’s wort.
If you are on Norvir and taking medications for other conditions, make sure your medical provider knows about all the medications you take, in order to help safeguard against potential interactions. The website HIV Drug Interactions has a helpful “interactions checker” where you can review potential interactions between medications you are on. You can also find useful drug-interaction information on the Department of Health and Human Services (DHHS) website on ART.
What’s the Verdict on Norvir?
Norvir is an old-school HIV medication from the 1990s that enjoyed an evolution and resurgence in utility in the 2000s due to its effectiveness as a booster medication that makes other HIV drugs work better.
While still used in some settings and circumstances, the ship has sailed on Norvir being incorporated in current ART regimens, particularly for individuals who have recently received a new HIV diagnosis. The combination of gastrointestinal side effects and pill burden is a deal breaker for many, and with the advent of both single-tablet regimens with minimal side effects and other boosting medications like cobicistat that are created in coformulations and single-tablet regimens, it is likely that Norvir’s glory days as a go-to HIV medication are long gone.