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. 

Medical Debt is a Severe Financial Burden in the United States

By: Ranier Simons, ADAP Blog Guest Contributor

Medical debt is a major financial crisis in the United States. It is a major barrier to financial health and even physical health. Studies show that medical debt is negatively correlated with health issues. People who have problems paying their medical bills have a shorter life expectancy, poorer mental health, health issues like hypertension, and lower self-reported health status.[1] 

Photo Source: The Sycamore Institute

Even though over 90 percent of the U.S population has some semblance of health insurance, medical debt is still a pervasive and debilitating issue.[2] Present-day medical insurance plans have many cost-sharing requirements that saddle patients with bills they cannot pay. With high monthly premiums, these requirements, such as high deductibles and co-payments, result in bad life decisions. People face juggling basic needs such as food, clothing, and housing with paying medical bills generated by necessary care. Moreover, people borrow from family or even financial institutions, going into even further debt to take care of their medical bills.

The Kaiser Family Foundation published a brief shining light on the burden of medical debt in the United States. The overall finding was that the burden of medical debt is stratified along racial and economic lines, age cohorts, strength of insurance coverage, and health status. The data source was the Survey of Income and Program Participation (SIPP). Significant medical debt was defined as people who owed more than $250 in unpaid medical bills as of December 2019.[2]  The survey shows that people in the United States owe, at the minimum, approximately $195 billion in medical debt. Roughly six percent of adults have over $1,000 in medical debt, and one percent (about 3 million people) owe over $10,000.[2]

Photo Source: KFF

Along racial lines, African-Americans are reported to be more likely to have significant medical debt. Of the 9 percent of adults surveyed who meet the study threshold of high debt, 16 percent of those are non-Hispanic African-American. This contrasts to 9 percent of non-Hispanic White Americans and 4 percent of non-Hispanic Asian-Americans. Regarding gender, more women report having high medical debt than men; 11 percent and 8 percent, respectively. Part of this discrepancy could be attributed to women having lower incomes and increased healthcare expenditures associated with childbirth.

Unsurprisingly, older adults are more likely to have significant medical debt than younger people. However, there is a distinction apparent among those later in life. The report shows that the percentages decrease when older adults reach Medicare age. Twelve percent of adults aged 50-64 report significant medical debt, in contrast to 6 percent of those aged 65-79.[2] 

In terms of income, those with lower or moderate incomes are more likely to have high medical debt. Twelve percent of adults with incomes below 400% of the federal poverty level have such debt. Income is essential because some do not have liquid assets to pay out of pocket maximums, deductibles, and co-insurances, even with insurance. Sixteen percent of adults stated they would need to take on credit card debt to meet an unexpected $400 expense.[2] Four hundred dollars could easily be an emergency room visit co-pay for a privately insured person or even an urgent care visit for someone who was not insured.

Health status in combination with income is another relationship leading to medical debt. Those with more medical issues, by definition, have more medical expenditures due to chronic health maintenance needs, and higher utilization of services generates more bills that accumulate over time. Those with more serious medical issues cannot earn as much income being hindered physically by their medical problems in both ability and maintaining consistent employment.

Geography was also shown to be a factor by the report. People living in rural states in the South reported as being 12% of those reporting high medical debt, as opposed to 10% in the Midwest, 6% in the West, and 8% in the northeast. Related to this geographical distribution is Medicaid. Twelve states that have not expanded Medicaid under the Affordable Care Act are Alabama, Florida, Georgia, Kansas, Mississippi, North Carolina, South Carolina, South Dakota, Tennessee, Texas, Wisconsin, and Wyoming.[3]

The KFF report is proof that expanding coverage is not a panacea to alleviating the financial burden associated with medical debt. Effective change will come with restructuring healthcare finance, socioeconomic infrastructure, wholistic population needs assessment, and re-examining the country’s value system.

[1] Pellegrin, M. (2021, May 19). How medical debt affects health. Retrieved from https://www.sycamoreinstitutetn.org/how-medical-debt-affects-health/
[2] Rae, M., Claxton, G., Amin, K., Wager, E., Ortaliza, J., & Cox, Cynthia. (2022, March 10). The burden of medical debt in the United States. Retrieved from https://www.healthsystemtracker.org/brief/the-burden-of-medical-debt-in-the-united-states/
[3] Holahan, J., Buettgens, M., Banthin, J., & Simpson,M. (2021, June 30). Filling in the gap in states that have not expanded Medicaid eligibility. Retrieved from https://www.commonwealthfund.org/publications/issue-briefs/2021/jun/filling-gap-states-not-expanded-medicaid

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. 

Industry’s Changes to 340B Drug Discount Program

By: Brandon M. Macsata, CEO, ADAP Advocacy Association, and Jen Laws, President & CEO, Community Access National Network (CANN)

The Community Access National Network (CANN) and ADAP Advocacy Association, back in October 2020, issued a Dear Colleague letter to our industry partners in the pharmaceutical manufacturing space surrounding HIV therapies. We detailed our concerns regarding the 340B Discount Drug Program and the necessity to ensure safety-net public health programs do not “get caught in the crossfire between pharmaceutical companies and contract pharmacies.” Our efforts led to constructive conversation, as well as a commitment to protect patients access to timely, appropriate care and treatment. Essentially, we sought a “carve out” for certain Covered Entities, namely the Ryan White Grantees (“Grantees”) serving clients living with HIV/AIDS. 

Photo Source: CANN

In the time since, considering our collective concerns for the sustainability, stability, and honest efforts to provide necessary services to PLWAHA, many of our industry partners have ensured additional efforts at transparency and accountability do not add to already existing reporting burdens of the Grantees. We still contend that the carve-out is essential to avoiding possible damaging effects on the safety-net programs crucial to the HIV-positive community.

Unfortunately, a few of our industry partners have express concerns about “bad actors” trying to encroach on the federal grantee carve-outs industry partners have thus far offered in requesting additional reporting of 340B Covered Entities. It has been our earnest position that solving the problems facing the 340B Drug Discount Program are achieved in a way that preserves benefit to patients and intent of the program while protecting against bad actors. However, any effort requires a scalpel, not a hatchet. The carve-out of these additional reporting requirements, in light of the oversight already offered by being federal grantees, has helped our industry partners align their values with their actions in working to ensure program integrity and minimize risks to patient benefit. 

It is important to recognize the historical and current reality many Grantees face. Yet, should pharmaceutical manufacturers insist on blanket reporting requirements for all Covered Entities void of any carve-outs, it should be done by supporting these Grantees, and thus the services and medications their patients rely upon. We urge our industry partners to pair any new reporting requirements with funding for the following activities:

• necessary expertise to navigate the establishment of third-party administrator and contract pharmacy agreements.
• extend program initiation funding for the 3 years after qualification to meet the labor needs of fulfilling this reporting requirement.
• develop other programming clinics specifically identify to work collaboratively.

Whereas our two organizations have long-supported reforms to the 340B Drug Pricing Program, because they are overdue and opportunities exist to ensure every single penny squeezed out of the program directly benefits patients, let’s not throw the baby out with the bathwater. Provided our industry partners are genuine in their expression and desire to preserve 340B’s intent to benefit patients, the aforementioned steps are modest and support appropriate transparency and accountability.

Respectfully, we believe any genuine effort to introduce added reporting burden on Grantees, of which are already most closely monitored in the 340B space, must also include support to meet these burdens. Any adjustments to Grantees’ reporting supported by funding and programming designed for Grantees to be “set up for success” on all accounts. We believe our industry partners are up to the task at hand and maintain the integrity to align actions and values.

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.

A Rare Personal Appeal to My POZ Brothers & Sisters; Please Protect Yourself

By: Brandon M. Macsata, CEO, ADAP Advocacy Association

For nearly 15 years, I've had the distinct honor of serving as the CEO of the ADAP Advocacy Association. The position has afforded me the opportunity to advocate for greater access to care and treatment for people living with HIV/AIDS, as well as to encourage patients to become stronger self-advocates, and also to mentor some new advocates along the way. And although it is a rare occurrence for me, today I'm making a personal appeal to my POZ brothers and sisters to protect themselves against Covid-19. Please get vaccinated, and boosted!

Over the weekend, and only after playing the "rona-dodge-ball" game for over two years, my luck finally ran out and I tested positive for Covid-19. Last year, I had received both series of the Pfizer–BioNTech Covid-19 vaccine, as well as the first booster shot. I did so to protect myself as an immunocompromised patient, but more importantly to protect my son, Sebastian, who is too young to be vaxx'd. In retrospect, it was the best thing that I could have done for both him and me. 

My ongoing recovery from Covid-19 has also been helped with a prescription for Merck's monoclonal antibody, called molnupiravir. That, and a lot of fluids and rest.

Although vaccines don't guarantee full protection against acquiring Covid-19, they most certainly do provide undeniable protection after testing positive. I have experienced 48-hours of severe Flu-like symptoms, but it could've been much worse if I had been unvaccinated.

Too many people living with HIV/AIDS remain unvaccinated, and it is concerning to me. We've witnessed enough needless suffering from this coronavirus, and far too many deaths. Please don't ignore the facts made available by the U.S. Centers for Disease Control & Prevention on the rates of Covid-19 cases, associated hospitalization, and deaths by vaccination status. The broader issue isn't about protecting you from SARS-CoV-2 infection, but rather what will happen if you do indeed get it. It is undeniable the full vaccine series and booster is very likely to keep you out of the hospital, and more importantly, out of the funeral home.

Photo Source: CDC

My personal appeal comes in response to recent troubling conversations about vaccination hesitancy; one was with an unvaccinated young, African-American male, and another with an unvaccinated middle-aged, white female. The former believed the Covid-19 vaccinations actually cause people to get the coronavirus, and not provide any protection. The latter argued the unvaccinated were actually faring better against Covid-19 than their vaccinated (and boosted) peers. Neither of these beliefs could be further from the truth, but they exist. Unfortunately, a lot of misinformation is fueled by certain cable news outlets, social media-fueled conspiracy theories, and ill-informed politicians with bad hair lusting over sound bites.

The intersection between the HIV/AIDS epidemic and the Covid-19 pandemic has become the new normal. A recent headline in Business Insider read, "Over the last four decades, HIV/AIDS has killed at least 700,000 Americans. COVID-19 has killed more in two years." We've previously been down this road, together. So let's learn from the past!

The science and technology behind the current vaccinations against Covid-19 are deeply rooted in the same life-saving therapies we rely on to keep us all healthy...and alive! Why not embrace the Covid-19 vaccination as an extension of your HIV-related care and treatment? Why not trust in the advent of the medical and treatment advances to keep you healthy? Why not take a leap of faith the same way we'd collectively do, if a cure for HIV is eventually discovered?

There could be numerous reasons why protecting yourself against Covid-19 is important. For me, especially as a single parent, it is my son. The mental health toll that this pandemic has placed on me cannot be understated with respect to him. I lay awake at night playing the what if game. If something happens to me, then who will care for him? If I test positive, then will I expose him to this terrible illness? If he gets sick, then will he end up in the pediatric intensive care unit? What I do know, getting that jab in my arm is my best line of defense.

In other words, our choices have consequences.

If you're HIV-positive and still unvaccinated, then please... please... please protect yourself by getting vaccinated against this potentially deadly virus. Talk to your physician. Talk to your pharmacist. Talk to your social worker. Talk to your clergy. Talk to your vaccinated peers. I invite you to email me and let's set-up a time to talk about why it is so important to protect yourself and the people important to you. You're important to me, and that's why I'm making this rare appeal.

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.