A preliminary study to be presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Lisbon, Portugal (April 23-26), suggests that people living with HIV who are on antiretroviral therapy (ART) with protease inhibitors (PIs), may have a lower risk of COVID-19 infection. The study is being carried out by Dr Steve Nguala of the Center hospitalier intercommunal de Villeneuve-Saint-Georges and the General Hospital of Melun in France and his colleagues.
Despite these important findings, the authors emphasize that this is a small, early observational study and should not be taken as conclusive evidence that long-term use of protease inhibitors will protect people living with HIV versus COVID-19.
People living with HIV are at higher risk of community-acquired or opportunistic infections, but they do not appear to be at increased risk of severe COVID-19, possibly due to their use of ART. Antiretroviral therapy was proposed as a protective factor against Severe Acute Respiratory Syndrome (SARS) in 2003, but the small number of cases did not allow conclusions to be drawn.
Protease inhibitors, a class of antiviral drugs used to treat HIV, work by blocking an essential enzyme (called protease) that viruses need to replicate and infect more cells. Although they have not been shown to cure COVID-19 infections in the general population, their effectiveness in preventing COVID-19 is unknown.
To investigate this question further, Nguala and colleagues conducted a multicenter cohort study in six hospitals in Ile-de-France to assess the impact of long-term use of PI in HIV-positive patients on the incidence of HIV infection. COVID-19. Between May 1, 2020 and May 31, 2021, they registered 169 HIV-positive people who were treated with ART with PI and 338 HIV-positive patients on ART without PI. None of the participants had been previously diagnosed with COVID-19, the average age was 50 years (48% female; 52% male).
Among participants treated with PIs, more than three-quarters were taking darunavir/ritonavir (131/169; 77%), about 8% were taking atazanavir/ritonavir (14/169), and the remainder were treated with other PI (24/169; 14%). On average, they had been taking PIs for at least one year.
All patients had regular clinical assessments and screening for COVID-19 during routine HIV follow-up (every 6 months). Modeling was performed to identify potential risk factors associated with COVID-19.
Over one year of follow-up (with some patients lost to follow-up in both groups), 12% (18/153) of participants taking PIs and 22% (61/283) of those in the non-PI group contracted COVID-19 assessed by positive SARS-COV-2 serology at the end of the study, and four patients in the non-PI group were admitted to hospital with COVID-19.
After adjusting for factors linked to an increased risk of COVID-19, including gender, age, CD4 cell count, number of people living in the household, contact with a positive COVID-19 case, researchers found that patients in the protease inhibitor group were 70% less likely to be infected with COVID-19 than those in the non-PI group.
Patients in both groups who had contact with COVID-19 in the 14 days prior to their consultation were twice as likely to test positive for COVID-19; while those living in the same household with at least three other people were three times more likely to test positive; and those who had lost their sense of taste were six times more likely to be diagnosed with COVID-19 (see table in notes to editors).
Protease inhibitor drugs have a long history of use, a good safety profile, and are generally well tolerated. By attacking the virus before it has a chance to multiply, they potentially provide an opportunity to prevent the spread of infections and the mutation of future variants. The lower occurrence of COVID-19 in patients treated with a protease inhibitor regimen raises the question of a preventive effect that should be further investigated. Further studies with larger numbers of patients, and in randomized trials in people without HIV, are needed to confirm these preliminary results. The challenge will be to produce robust data within a limited timeframe that can inspire new prevention or therapeutic strategies. »
Dr Steve Nguala, Center Hospitalier Intercommunal de Villeneuve-Saint-Georges and General Hospital of Melun in France
European Society for Clinical Microbiology and Infectious Diseases