A HIV drug combination used to treat some coronavirus patients could cause their hearts to slow down or stop completely, doctors have warned.
A 67-year-old given lopinavir/ritonavir — which is being used experimentally around the world — needed a pacemaker to recover from his episode.
The man, who had high blood pressure and coronary artery disease, was given the drugs after catching Covid-19 and ending up in hospital.
And within days the unnamed patient in the case report — at a hospital in Singapore — saw his resting heart rate drop from 84 beats per minute, within the healthy range, to below 30.
His blood pressure also dropped to a dangerously low level and doctors had to fit a pacemaker to restore his heart to a healthy function.
The medics have now warned the drug combination — marketed as Kaletra — should be used with caution in patients who already have heart problems.
It is still not clear whether lopinavir/ritonavir — an antiviral which can prevent viruses from reproducing — protects against Covid-19. But studies suggest it could shorten recovery time.
But it is a known possible side effect of the drug that it can interfere with the heart, causing it to slow down and even stop because it interferes with electrical signals in the body.
A 67-year-old coronavirus patient almost died after his heart stopped when he was given a promising drug (pictured, lopinavir/ritonavir – brand name Kaletra) in a bid to cure his disease
Kaletra is one of dozens of drugs being trialed on Covid-19 patients around the world.
However, the World Health Organization announced at the beginning of July that it was no longer recommending the drug’s use because it ‘produced little or no reduction in the mortality of hospitalised Covid-19 patients when compared to standard of care’.
In the report from experts in the National University Health System in Singapore, the unidentified coronavirus patient was given the drug 10 days after he developed Covid-19 symptoms when his condition severely deteriorated.
His heart rate, which had started off at a healthy 84bpm, plummeted to 30bpm just three days after he was given the drug and his blood pressure dropped to dangerous levels. A normal rate is between 60 and 100.
WHAT IS LOPINAVIR/ RITONAVIR?
Lopinavir/ritonavir is a fixed-dose combination medication used mainly for the treatment and prevention of HIV.
It combines lopinavir – a substance that helps to stop viruses from being able to reproduce inside the body – with ritonavir – a substance that slows the breakdown of the lopinavir.
It was first approved as a single medication in the US in 2000 and is currently on the World Health Organization’s list of essential medicines.
It is taken as a capsule or in a solution but can also be injected.
The drug is known to produce a number of adverse side effects including: Diarrhea, headache, weakness, nausea, vomiting, stomach upset, drowsiness, dizziness, a bad taste in the mouth, trouble sleeping, skin rash, and changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).
There are other more serious side effects caused by the drug, one of which is bradyarrythmia (when the heart slows below 60bpm).
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Doctors were forced to attach him to a temporary electric pacemaker to regulate his heartbeat, something the authors of the report deemed to have been life-saving — especially during a pandemic when precious seconds could be lost while doctors put on protective equipment before resuscitating a dying patient.
The authors wrote: ‘This could be life-saving as delays in attending to emergencies are expected, due to the need to don personal protective equipment.’
Even the pacemaker struggled to regulate the patient’s heartbeat and backups were needed throughout the rest of the day but the medics didn’t reveal exactly why this happened.
Doctors then decided to take him off the drug and his heart rate stayed stable over the next two days. He then fully recovered.
In hindsight, the experts have said doctors should think carefully about whether to give Kaletra to Covid-19 patients who already have heart problems, and to consider putting pacemakers in straight away if they do decide to use the treatment.
The heart problem suffered by the man is known as a bradyarrhythmia — a sudden drop in the heartbeat because of an interruption to the electrical signals which control the organ’s tempo.
Bradyarrhythmia can cause the blood pressure to drop and oxygen levels to fall, leading to dizziness, fainting, shortness of breath, chest pain and tiredness.
Lopinavir/ritonavir can trigger this because it works by blocking electrical signals.
Because of the way it works the drug can block the hERG gene (The Human Ether-a-go-go gene), which helps to regulate heart beats, from being able to work properly.
In rare cases, HIV patients have suffered heart blocks – when the organ slows down and in severe cases, stops beating because of an interruption in the electric impulses that the brain sends it – after taking the drug.
Doctors in France found in July that administering the drug caused bradyarrthymia in nine out of 41 Covid-19 patients after 48 hours of administration.
Once doctors stopped giving the patients the drug, their heart rates went back to normal.
They wrote: ‘After cessation of lopinavir/ritonavir, no further bradyarrhythmias were observed.’
The authors noted that ‘current evidence on the efficacy and safety of any protease inhibitors for treating Covid-19 infection is debated’.
One study from January at the Jin Yin-Tan Hospital in Wuhan – the centre of the outbreak of coronavirus – found there was no difference between coronavirus patients treated with lopinavir ritonavir compared to those given ‘standard care’.
The authors split a group of 199 coronavirus patients into two groups of 100 and 99. The group of 99 patients was given lopinavir/ritonavir.
The authors noted that there wasn’t a significant difference in the time it took patients to recover and in roughly the same number of people in each group died.
They concluded that this showed using the drug was not beneficial. However, a review of the study noted that coronavirus patients who were given the drug had shorter stays in ICUs and shorter hospital stays in general.
The review added that there were also fewer complications in the group that was given lopinavir ritonavir and the only patients who had to be taken off the drug were ones who suffered severe gastrointestinal effects.
The most recent report, published in the Journal of Microbiology Immunology and Infection, suggests that if lopinavir/ritonavir is used then a pacemaker should be attached before just in case it causes a massive reduction in heart rate.
They believe their patient is the first reported case of a coronavirus sufferer needing a temporary pacemaker because of long gaps between heartbeats.
However they noted that one patient previously had a problem with electrical signals getting to his heart and it stopped beating.
And another two cases were found who suffered from similar problems and an arrhythmic heartbeat.
Tests of lopinavir + ritonavir have come amid a global scramble to find drugs that work on Covid-19 patients to reduce their risk of dying.
Only one drug so far has been proven to work – a £5 steroid called dexamethasone.
An Oxford University scientist who led a British trial of the drug, Professor Peter Horby, said that every eight people treated with the drug could save one life and cost just £40 in total.
It could save up to 35 per cent of patients relying on ventilators – the most dangerously ill – and reduce the odds of death by a fifth for all patients needing oxygen at any point.
And another drug initially developed to treat Ebola, remdesivir, has also shown promising results when treating Covid-19 patients.
Gilead Sciences, a California-based company that developed the drug, reported that after 11 days patients taking the drug showed small signs of improvement. It was the first medicine approved by the NHS to specifically treat coronavirus patients, and UK Health Secretary Matt Hancock said at the time that the approval had been the ‘biggest step forward’ so far in treatment of the disease.
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