- Barcelona doctors reported on the cases of five HIV-positive patients with COVID-19
- These patients represented 1% of all hospital patients diagnosed with the coronavirus
- Four of the patients have recovered, and their cases may offer guidance to clinicians
Doctors at the University of Barcelona, Spain, have published a detailed report on five people with HIV who were co-infected with SARS-CoV-2, the virus that causes coronavirus disease-2019 (COVID-19). All were under the age of 50 and four out of the five people had recovered from COVID-19 at the time of publication. The report from Barcelona is a small case series and no firm conclusions can be drawn about the effectiveness of the potential anti-SARS-CoV-2 treatments.
Case details
The doctors stated that by March 9, 2020, the University’s hospital clinic had admitted 543 people who were diagnosed with SARS-CoV-2 infection. Five of these people (about 1%) were HIV positive—three were men who had sex with men (MSM) and two were transgender. The five people sought care because they had fever and cough and, in some cases, other symptoms (such as lack of energy, shortness of breath and headache). Underlying health conditions were only noted for two people—one man had lower-than-normal levels of thyroid hormones in the blood (hypothyroidism) and another man had asthma.
All of the people with COVID-19 underwent a chest X-ray. In two people with mild COVID-19, the X-ray images were clear. In the remaining three people, the X-ray images were suggestive of an infection or pneumonia. In these three people COVID-19 was assessed as severe (two people) or moderate (one person).
Four of the five people were taking HIV treatment prior to their admission to hospital. Their CD4+ cell counts were greater than 400 cells/mm3 and their viral loads were undetectable (less than 50 copies/mL). The fifth person was diagnosed with HIV while hospitalized, with a CD4+ count of 13 cells/mm3 and a viral load of 45,500 copies/mL.
The HIV treatments (ART) taken prior to hospitalization were as follows:
- darunavir + cobicistat + TAF + FTC – two people
- dolutegravir + abacavir + 3TC – two people
Revisiting Kaletra
There is no treatment or combination of treatments that is approved in Canada or other high-income countries for SARS-CoV-2 infection. However, in the current emergency situation, doctors caring for people with COVID-19 may choose to prescribe an unusual combination of drugs in the hope of keeping people alive, particularly those with severe symptoms.
In theory, an older class of HIV drugs called protease inhibitors might inhibit an enzyme used by SARS-CoV-2. One HIV protease inhibitor is called lopinavir. It is available in a fixed-dose formulation with a small dose of another drug called ritonavir. The purpose of ritonavir is to raise or boost levels of lopinavir so that twice- or once-daily dosing is possible. This small dose of ritonavir has no antiviral activity. Lopinavir-ritonavir is sold under the brand name Kaletra and is available in generic formulations. Kaletra was once widely used as part of HIV combination therapy in Canada and other high-income countries. However, over the past 15 years it has been replaced by more potent and better-tolerated medicines.
A clinical trial of Kaletra recently found that it did not have significant clinical benefit in people with severe symptoms of COVID-19. However, other clinical trials of Kaletra in COVID-19 are underway.
Another HIV protease inhibitor, darunavir, was reputed to have anti-SARS-CoV-2 activity, but the manufacturer, Janssen, performed lab experiments with cells and this virus and found that darunavir did not have significant effects.
Some changes to regimens
The person with moderate COVID-19 symptoms was kept on their pre-hospital darunavir-based regimen and did not receive additional interventions (see below). Another person who was diagnosed with HIV in the hospital had severely depleted CD4+ cell counts and was given darunavir-based ART, as they had developed life-threatening pneumonia that is the hallmark of AIDS (pneumocystis pneumonia, or PCP). For the remaining three people, doctors explained that they were going to change their HIV regimens to one based on Kaletra because, they said, it “might” have antiviral activity against SARS-CoV-2. Once people recovered from COVID-19 doctors would reinstitute their previous HIV treatments. Doctors instituted the following new regimen designed for COVID-19 and HIV:
- Kaletra + Truvada
Truvada was added to help maintain HIV suppression.
Additional interventions
As part of an anti-SARS-CoV-2 regimen, some people received additional treatments:
- Two people received interferon beta-1b, at a dose of 8 million units every 48 hours via injection for several days.
- Four people received hydroxychloroquine, at a dose of 400 mg twice daily on the first day and then 200 mg twice daily for four days.
- Three people received the antibiotic azithromycin, at a dose of 500 mg on the first day followed by 250 mg per day for four consecutive days.
None of these interventions have been proven effective against SARS-CoV-2, but they appear promising in lab experiments with cells and the virus and in small studies with people. These drugs are in clinical trials and/or were widely used by doctors in China in the early part of the pandemic.
The person with PCP received additional antibiotics for this pneumonia—trimethoprim-sulfamethoxazole for 21 days.
One of the people with severe COVID-19 was given the powerful anti-inflammatory drug tocilizumab, a one-time injection of 400 mg. This drug is used for the treatment of arthritis and suppresses a chemical signal called IL-6 (interleukin-6) that incites inflammation. Some scientists suspect that the severe lung injury associated with some cases of COVID-19 may be caused in part by the immune system releasing inflammatory chemical signals.
Results
Four people were subsequently assessed as cured from SARS-CoV-2 and discharged from the hospital.
However, one person who was on HIV treatment prior to hospitalization has remained hospitalized and is in intensive care. His lungs are severely injured and do not work properly. As a result, doctors have had to pass his blood through an external apparatus that enriches it with oxygen and removes carbon dioxide. The blood is then returned to his circulation. This process of external oxygenation is called ECMO (extracorporeal membrane oxygenation). ECMO has been used around the world in cases of severe lung injury arising from COVID-19.
Bear in mind
The Barcelona doctors made the following points about the five people under their care:
- HIV-positive people have so far accounted for about 1% of people hospitalized with COVID-19 in their hospital.
- They were all under the age of 50.
- As most of the people in this case series were transgender or MSM, the doctors called for research with other populations who have HIV and who develop COVID-19, such as older MSM, substance users, women and heterosexual men.
- The doctors noted that two people in the case series “were sex workers, one reported participating in a chemsex party six days prior to admission to hospital. During this pandemic, implementing health education programmes is very important to [help] explain that such activities as these could cause clusters of SARS-CoV-2 transmission.”
- It is possible that some people with previously undiagnosed HIV infection will develop COVID-19 and AIDS-related pneumonia in the future. The Barcelona doctors encourage other clinicians to be vigilant for such a situation.
–Sean R. Hosein
Resources
Kaletra disappointing in people severely ill with COVID-19 – CATIE News
Coronavirus disease (COVID-19): Outbreak update – Public Health Agency of Canada
Having sex and staying safe during the COVID-19 pandemic – Health Initiative for Men
Coronavirus COVID-19 – Terrence Higgins Trust
COVID-19: What people with HIV should know – US Centers for Disease Control and Prevention (CDC)
Interim guidance for COVID-19 and persons with HIV – US Department of Health and Human Services
REFERENCE:
Blanco JL, Ambrosioni J, Garcia F, et al. COVID-19 in patients with HIV: Clinical case series. Lancet HIV. 2020; in press.