Protease Inhibitors and Integrase Inhibitors Show Early Promise in Protecting Against Covid-19

By: Ranier Simons, ADAP Blog Guest Contributor

The scientific and medical world is still actively researching and learning about Covid-19. This is especially true regarding how Covid-19 affects the populations of people living with HIV. Generally, HIV-positive people are more susceptible to community-spread diseases or opportunistic infections. However, current research indicates that people living with HIV are not at increased risk for severe COVID-19 illness or hospitalization.[1] This realization is only valid for HIV -positive people who have healthy CD4 counts greater than 200 and are on a consistent, stable medication regimen. Those with advanced HIV disease and low CD4 counts do not fare as well. Ongoing research also shows that unvaccinated HIV-positive people are more likely to develop long Covid.[2] 

Photo Source: AIDSmap

Not only are otherwise healthy HIV-positive individuals not at a higher risk for Covid-19, but small early studies suggest that they may be at a lower risk due to their antiretroviral therapy (ART). Specifically, protease inhibitors and integrase inhibitors show early promise in protecting against Covid-19.

One such study, presented at the European Congress of Clinical Microbiology & Infectious Diseases this week in Lisbon, Portugal, shows promise in protease inhibitors. Protease inhibitors work by blocking a critical enzyme viruses, like HIV, need for replication which allows infection of more cells.[1] This study was a multicenter cohort study that examined how long-term usage of protease inhibitors (PI) influenced the incidence of Covid-19. The study group was 169 people with HIV on ART with PI and 338 HIV patients on ART without PI. None of the patients had ever contracted Covid-19. They had been on PI treatment for at least a year.

Seventy-seven percent of the PI group was treated with darunavir/ritonavir, 8 percent with atazanavir/ritonavir, and the remainder used other PI’s. After being followed for a year, 12 percent of those treated with PI’s contracted Covid-19 compared to 22 percent of those in the non-PI group.[1] This is an observational study and cannot be used to imply direct proven clinical causality. Yet, it is a promising step of initial inquiry.

Photo Source: Viral Zone

Integrase Inhibitors are the focus of another recent study. In a study recently published in the International Journal of Molecular Sciences, researchers report two drugs that prevent SARS-CoV-2 (Covid-19) from entering host cells. SARS-CoV-2 enters cells via a pathway involving its spike protein (S) and the angiotensin-converting enzyme 2 (ACE2) receptor on host cells. Utilizing an assay they developed to detect the interaction between S and ACE2; scientists selected a library of drugs to screen in regards to possibly preventing the interaction.[3] Out of the 1068 integrase inhibitors considered, Dolutegravir and Etravirine were the most successful at prohibiting SARS-CoV-2 into host cells.[3] They were both also found to be effective at neutralizing the Omicron variant as well as wild-type virus and other variants of concern. 

Investigating the possible Covid-19 protection offered by protease and integrase inhibitors may lead to additional weapons in the arsenal against Covid-19. Utilizing these drugs’ off-label effects could lead to new pre/post-exposure prophylactic treatments for Covid-19 infection.

[1] Henderson, E. (2022, March 27). HIV patients on antiretroviral treatment with protease inhibitors may have lower COVID-19 risk. Retrieved from https://www.news-medical.net/news/20220327/HIV-patients-on-antiretroviral-treatment-with-protease-inhibitors-may-have-lower-COVID-19-risk.aspx
[2] Alcorn, K. (2022, March). COVID-19 and coronavirus in people living with HIV. Retrieved from  https://www.aidsmap.com/about-hiv/covid-19-and-coronavirus-people-living-hiv
[3] Lee, R. et al. (2022) "Identification of Entry Inhibitors against Delta and Omicron Variants of SARS-CoV-2", International Journal of Molecular Sciences, 23(7), p. 4050. doi: 10.3390/ijms23074050.https://www.mdpi.com/1422-0067/23/7/4050

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.