Assessing Kaletra for COVID-19

Segment description: Krutika N. Mediwala, PharmD, BCPS, BCIDP, clinical pharmacy specialist in infectious diseases and antimicrobial stewardship at MUSC Health, provides a recap of available information regarding Kaletra for the treatment of COVID-19.

Interview transcript (modified slightly for readability):

Contagion®: Thanks for joining us for another Contagion® coronavirus video. Today we will be talking about Kaletra.

Our guest today is Dr. Krutika Mediwala, who recently hosted a webinar on the SIDP website about Kaletra. Thanks for joining me, let's get started. Can you describe the mechanism of action of Kaletra?

Mediwala: Thanks a lot for having me on. Kaletra works as an antiviral agent for HIV. It’s been part of our post-exposure prophylaxis. It actually works when inhibiting the HIV-1 protease purview, which leads to the formation of some immature and non-infectious viral particles. This is similar to what we hypothesize in the SARS coronavirus, except the main protease in SARS (severe acute respiratory syndrome) is the Chymotrypsin-like Protease, and that's where we hypothesize Kaletra may inhibit this protease, leading to similar results, such as HIV. Then we also have that ritonavir component in the combo that inhibits . We have increased serum levels in the drug combo.

Contagion®: Great, thank you. What are some of the existing data that we have on Kaletra with other coronaviruses, like SARS or MERS (Middle East respiratory syndrome)?

Mediwala: There are quite a few data for SARS and MERS when Kaletra comes into the picture. There are in vitro data, however, they are kind of equivocal, there's various EC50s, 50% effective concentration that's needed. Most of them say that with no help from ritonavir as well. In my research, I was able to find some positives and some not so positives to balance out the data.

For animal data, there's really not that anything that I could find in SARS, though MERS does have some data in primates and mice. There was a study in primates where they compared an untreated control, 1 with mycophenolate and another group with interferon and then a Kaletra group.

The Kaletra group demonstrated that they have improved clinical scores, and for some a lower mean viral load in the lungs. In mice models, they compared it to remdesivir and interferon, what they found was it did not display any superior activity when they compared it to the 2 other drugs.

When it comes to human data, most of them have been done in combo with ribavirin and steroids. So all the studies will have that as a component and then they either add Kaletra or not to the treatment group. In SARS it shows that early use may show less intubation in patients, have less corticosteroids needed, and even less risk of death. They did another study that showed significantly less patients develop ARDS within 21 days of discharge.

For MERS, and this was kind of a unique study, they did 1 in post-exposure prophylaxis in health care workers and that showed that giving patients this drug in combination with some of the supportive care showed a 40% decrease in risk of subsequent MERS-infection. They don't talk a lot about some of the adverse events that could take place. We'll talk a little bit about that later on, but no severe adverse drug events were noted in any of these studies.

Contagion®: Thank you for that information. My next question is: Kaletra has been studied in an open label individualized trial in China. So what data have we seen from that research so far?

Mediwala: Before this open label, individualized trial in China there were a couple of case reports, but this essentially sealed the deal for use of Kaletra in these patients. So they looked at some SARS-CoV positive, PCR-positive patients, and they compared them to standard care plus Kaletra or just standard care. That was just symptomatic therapy mostly.

What they found was there was no difference in the primary outcome and time to clinical improvement or mortality. They also didn't find any increase in the viral loads with Kaletra either. I did want to point out that the median time before symptom onset to randomization was about 13 days. So that's kind of a long time when you're looking at COVID-19. They did have a high mortality rate of about 22%, they had some 36 patients that they looked at in this study, which is helpful.

Contagion®: Great, thank you so much for that summary of that data. Are there any serious concerns associated with kaletra in regards to adverse reactions, or any drug-drug interactions?

Mediwala: Kaletra does have adverse reactions, so these can be some hypersensitivity reactions. It can prolong the QT and cause some arrhythmias. It also has a lot of adverse events related to some type of hypotriglyceridemia, anemia, leukopenia, neutropenia.

Most of the studies report nausea, vomiting, diarrhea, as some of the most common adverse events. It is contraindicated in some severe cardiac disease, where the patient already has cardiomyopathy and QT prolongation. If you look at our patients that are really at high risk of COVID-19, you've heard a lot about patients with cardiac diseases being at high risk of acquisition as well as mortality.

The last thing when it comes to drug-drug interaction is that ritonavir component for inhibition interacts with some of our other HIV meds, our hepatitis C meds, some antifungals, some of these drugs that are really important for immunocompromised patients.

Contagion®: My next question for you is actually one that we received from an attendee of a contagion webinar that we had this past week. And that audience member wanted to ask if you have any comments on the ribavirin and Kaletra combination?

Mediwala: Most of the studies with Kaletra did have ribavirin on as well as one of the standards of therapy, and then plus/minus, they had steroids as well. And so to look at that literature, the Kaletra dose studied was going from 1.2 to 2.4 grams, up to 3 times a day. And that compared to what we normally use ribavirin for those doses have very, very high. And we really worry about the tolerability of the toxicity that this can cause in our patients. Specifically, the risk of hemorrhagic toxicity is too high.

Contagion®: Based on all of the data that you've included, and the available information, what is your final opinion on kaletra in regard to COVID-19 treatment.

Mediwala: I think kaletra does not appear to have any clinical benefits and clinical improvement or consistent viral load in SARS-CoV-2. That being said we have other options that have come into the front line. We really need a little bit more data, we've had a total of 3 to 4 studies.

Contagion®: My last question for you is, what is your advice to clinicians who are trying to stay up to date on all of the news coming out about COVID-19, while also treating patients and trying to stay focused on treatment?

Mediwala: Obviously the Contagion® website, and then Twitter.

I hop on Twitter twice a day, for a literature check and to see what has come out. There are some accounts that are really good to follow that really are on top of things. But that being said, we are in a time where we are trying to push for information to get out there so quickly.

I take what is out there and then discuss it with my colleagues. I call it my internal peer review of what is out there because I appreciate the transparency but we still need to be really diligent in doing the work that it takes to really look at the flaws of a study, the process of a study, is it feasible to do it in our population?

Contagion®: Thank you so much for joining us today. And for anyone who's interested in watching the SIDP webinar, you can access that on their website. So thanks again, and stay well.

Mediwala: Thanks for having me on.

Mediawala is an active member of the Society of Infectious Diseases Pharmacists. Her webinar presentation is available here.