Since the first article I wrote addressing the coronavirus epidemic a couple of weeks ago (posted February 26, 2020 Coronavirus section of Health Conditions), some things have changed and some things have not. What has changed is the number of cases in the US and sadly, the number of deaths.
They have increased dramatically! That will continue to be the case for some time. There’s still a lot we just don’t know. Effectively tracking the virus and even understanding just how lethal the infection becomes virtually impossible if we cannot test for it. The failure to have an effective test widely available, not only to screen for potential infections but to get estimates on the prevalence (how common the disease is in the population) of the infection and also for conducting surveillance, seriously hampers efforts to control the infection. This represents a seriously missed opportunity.
I hope that by the time you read this that this situation has been remedied. We still need to make sure we have enough intensive care hospital beds and ventilators; we may not. We are also learning that this infection is much more serious in younger people than we once thought. It is imperative to follow the guidelines (social distancing, hand washing, staying home if sick) and check-in regularly with your Public Health agencies. If you feel sick, call your medical provider or local hospital first to get specific instructions. You do not want to be sitting around in a waiting area. There will not be an effective vaccine anytime soon (if ever) so don’t count on that. Besides preventing infections, we need some drugs that can slow the virus down. Can the treatment of HIV help us in any way?
Kaletra for COVID-19?
While there are no approved drugs to treat COVID-19 disease as of yet, it appears possible that HIV could help provide some solutions.
You May Also Like
In 2003 when there was a serious global outbreak of the SARS Coronavirus, it was discovered that the HIV medicine Kaletra was helpful in getting people with the SARS respiratory distress syndrome to recover from this potentially fatal condition. So how could this work?
Kaletra is a combination drug in the class called protease inhibitors. Recall that viruses use our cells as factories to make more viruses. The HIV virus is made up of four structural proteins. HIV maximizes efficiency when it highjacks our cells. Instead of producing the four structural proteins separately, the four proteins are produced as a single long protein.
Then HIV produces an enzyme called the HIV protease and this enzyme acts like a pair of scissors and cuts the single long protein into the four structural proteins. Those four proteins then become assembled into a new HIV virus that will be released from the cell along with thousands of other new viruses to infect other cells. The drug Kaletra blocks the HIV protease, so the HIV structural proteins don’t get produced and new viruses can’t be assembled.
Coronaviruses, while quite different from HIV (lentiviruses), use a similar strategy producing a single protein that requires a coronavirus protease to release the coronavirus structural proteins. In the lab, we can show the ability of Kaletra to block infections with the new coronavirus.
You May Also Like
This new coronavirus that causes COVID-19 is closely related to the SARS coronavirus. There are some studies, mainly in China, that showed Kaletra was helpful in patients with SARS coronavirus. So is there any evidence that Kaletra will work against COVID-19? There seem to be isolated reports of a potential benefit, but nothing is conclusive and the reports are somewhat limited. Time will tell. Studies are ongoing.
Here in the US, Kaletra is not the preferred protease inhibitor drug for treating HIV. Patients are more likely to be on Atazanavir (Reyataz) or Darunavir (Prezista) which, unlike Kaletra, are dosed once a day and have few side-effects. The good news is Kaletra is widely available in developing countries so if it does have any value in treating COVID-19, anyone can get it.
Alpha-interferon 2b for treating COVID-19?
Interferons are natural proteins that our bodies produce to protect us from viral infections. There is a family of interferons and they have protective actions against most types of viruses. When a virus infects a cell, signals in the cell trigger the production of interferon. Interferon can destroy the viral genetic material so that it cannot reproduce.
Interferons are then released from infected cells and entered uninfected cells and work to protect them from getting infected. While the interferon system is a great mechanism for fighting viruses, some viruses have developed ways to block interferon’s protection and get around its effects.
Alpha-interferon was once used to treat Hepatitis C infection in combination with a drug called ribavirin. Since it is a protein, it cannot be given orally and must be injected intravenously or under the skin like insulin. The doses of interferon used were high and produced many side-effects which are also the case for ribavirin. Also, this combination often failed in curing African-Americans of the disease.
Now, we have combination drugs in a single pill that can cure Hepatitis C in just a couple of months.
But prior to its use in Hepatitis C (and also in hepatitis B), interferon was explored extensively for the treatment of HIV infection. Prior to the availability of potent combination therapy, interferon at fairly high-doses showed some success in treating the cancer Kaposi’s Sarcoma in HIV patients.
Other studies also showed some ability of interferon to lower viral load, especially when combined with other HIV drugs, but not to undetectable levels as we see with the current combination therapies. In the early nineties, there were only a couple of HIV medicines available (AZT/zidovudine, ddI/didanosine) and these were fairly weak and not able to suppress the virus significantly as single drugs.
In addition, they required multiple doses a day and had significant side-effects and toxicities. Other alternatives were desperately sought and studies coming out of Africa at the Kenya Medical Research Institute suggested that low-doses of alpha-interferon taken sublingually (under the tongue) could be effective in HIV disease. In African-American communities, there was a lot of interest in this potential therapy, however, the clinical trials did not show much promise. Combination therapy for HIV disease became available around 1996.
Because of the broad actions of interferons across many types of viruses, it is reasonable to test its effect against COVID-19. Studies are underway.
Remdesivir for COVID-19?
This experimental drug for COVID-19 may be our best bet. It is not currently available for any other use and has not been looked at for HIV disease, though the drug does work against coronaviruses similar to some HIV drugs (nucleoside analogues).
Clinical trials of Remdesivir are ongoing and hopefully, we will see some benefit soon.
Please Note!!! The drugs discussed here HAVE NOT BEEN PROVEN TO BE EFFECTIVE FOR COVID-19!
They may have been effective in the laboratory or for the patient with other coronavirus infections so they are being studied and we will hopefully have some results soon. Keep your fingers crossed.
In the meantime, follow the guidelines from your Public Health Agency and take this pandemic seriously!
