Showing posts with label Integrase Inhibitors. Show all posts
Showing posts with label Integrase Inhibitors. Show all posts

Thursday, April 28, 2022

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] 

Image of coronavirus
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.

Protease Inhibitors
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.