Welcome to our series, 1 Big Question, which asks 1 question to the medical community and we get their feedback on an important infectious disease topic.

In this episode, our 1 Big Question is: Looking at C diff as a whole, would you say the medical community is doing a better job overall of treatment and what challenges remain?

We interviewed Sahil Khanna, MBBS, MS, who is professor of Medicine in the Division of Gastroenterology and Hepatology at Mayo Clinic; Glenn Tillotson, PhD, FIDSA, FCCP, GST Micro LLC; Payal K. Patel, MD, MPH, Division of Infectious Diseases assistant professor, University of Michigan Health System and medical director of Antimicrobial Stewardship, VA Ann Arbor; and Anurag Malani, MD, infectious diseases specialist, St. Joseph Hospital, and a fellow of Infectious Diseases Society of America (IDSA).

Check out our video to hear their insights.

Videos

What are the efforts being made with antibiotic stewardship and treatments, and what areas in clinical care do medical professionals want to see improvements.  

Where Are We With Clostridioides Difficile?

Recently, over 50 major healthcare organizations 

 that called for all healthcare employers, from hospitals to long-term care facilities, to require a COVID-19 vaccine for their employees.

The authors and signatories of that statement cited their reasoning as the protection and safety of not only the healthcare workers themselves, but that of their patients and residents as well.

The healthcare sector, the authors stated, should be a leader when it comes to being vaccinated against 

However, by the end of May, 1 in 4 healthcare employees still didn’t receive a shot, proving there is still a considerable amount of hesitancy in that population.

When it comes to information about vaccines, there is hardly a more knowledge group of individuals than pharmacists. Not only do they know about the medicine itself, but they must be familiar with the entire approval process that a therapy goes through.

So, what role do they play in vaccine advocacy?

Anna Legreid Dopp, Pharm. D, senior director of clinical guidelines and quality improvement at the American Society of Health-System Pharmacists, discussed this topic in a recent interview with 

“As a trusted voice in the community, pharmacists are one of the most accessible healthcare providers,” Dopp said. “They can manage care concerns, they can triage care concerns and having those one on one conversations knowing that the pharmacists understand it, I think they should be leveraged to have those crucial conversations.”

In the interview, Dr. Dopp also discusses the varying reasons why there is still vaccine hesitancy in the healthcare worker population and how pharmacists can use their voice to be champions of vaccination.

Articles

A conversation with Anna Legreid Dopp, Pharm. D.

What Role Do Pharmacists Have in Vaccine Advocacy?

Preferred HIV treatment among patient populations is diversified; among housing-compromised persons, even more factors come into play.

As described in a new study presented at the 

International AIDS Society (IAS) 2021 Conference on HIV Science

 last week, homeless or people with unstable housing living with HIV provided varied feedback on care models preference, physician continuity needs, telehealth resourcing, and incentive-based care.

The findings, presented by Elizabeth Imbert, MD, MPH, associate professor at UCSF and clinical lead of the trial’s POP-UP Program at Ward 86 in San Francisco, suggest the need for more focused care toward the homeless HIV population.

In the second segment of an interview with 

 during IAS 2021, Imbert explained the observed populations’ HIV care preference particularities, such as that with Telehealth.

“I think one of the take-home messages from this is that folks who are homeless or unstably housed with HIV, during COVID-19, did not prefer telehealth, even when we said, ‘Someone can come to you,’” Imbert said. “To me, as a provider, that says we should keep our doors open, because these folks are vulnerable.”

Imbert also discussed the need for personable, tailored care from consistent caregivers dedicated to this HIV population.

A discussion as to why people with unstable housing living with HIV may not prefer telehealth versus consistent in-person care.

Can We Provide Tailored Care for Homeless HIV Patients?

 last week showed COVID-19 severity risks were not more significantly associated with hospitalized people living with HIV.

The findings, presented by author Matthew S. Durstenfeld, MD, Assistant Professor of Medicine in the UCSF Division of Cardiology, dissented from previously-held beliefs that people living with HIV—particularly those receiving therapy—may be at a greater risk of COVID-19 severe illness or even death due to their status.

during IAS 2021, Durstenfeld discussed the early-pandemic uncertainty as to whether immunosuppressed patients on antiretroviral therapy would be compromised in COVID-19 risks.

“I think now we know that’s not the case—that we can treat people living with HIV, at least in the states where the vast majority are, I think we can treat just like any other person,” Durstenfeld explained. “They don’t need a special kind of observational status while we figure that out anymore.”

Durstenfeld additionally discussed the surprising lack of data available for the team’s research.

“The fact it took us including over 21,000 people to find 220 people living with HIV is pretty remarkable and speaks to the fact if people living with HIV were hospitalized at dramatically higher rates, then we would have expected that number to be higher,” he explained.

The risk of COVID-19 severity in people living with HIV may be less than previously anticipated.

Shifting COVID-19 Concerns in the HIV Community

New trial data from Merck showed investigative once-monthly 

 islatravir was associated with good tolerability and predominately mild adverse events versus placebo among patients at low-risk of HIV-1 infection, in 24-week, phase 2A trial data.

The findings, presented this week at the 

, alluded to the therapeutic potential of a longer-duration PrEP option among a broad patient population.

But ongoing phase 3 trials may better inform its absolute potential among other available PrEP.

during IAS 2021, study author Sharon Hillier, PhD, director of Reproductive Infectious Disease Research at UPMC Magee-Womens Hospital in Pittsburgh, discussed the 2 ongoing phase 3 studies for islatravir, in which the agent is being observed for HIV incidence versus available once-daily, fixed-dose marketed PrEP, as well as in populations such as men who have sex with men and transgender women.

As Hillier explained, the trials will help inform investigators as to whether a once-monthly PrEP is as good, if not better, than once-daily combinations.

“And ‘better’ can be a number of things,” Hillier explained. “Better at blocking HIV, or more tolerable, or easier to adhere to.”

Hillier also shared perspective on the aging HIV-risk population, and how research can continue to assure therapeutic prophylaxes are tailored to their needs.

Phase 3 trials for islatravir are underway. What are investigators considering with the Merck investigative drug?

Once-Monthly PrEP May Become a Viable HIV Option

 market is emerging as different medications and treatment options are being studied, there are 2 therapies that are Food and Drug Administration (FDA) approved currently: emtricitabine and tenofovir alafenamide (F/TAF), and emtricitabine and tenofovir disoproxil fumarate (F/TDF). Each of these medications are indicated for a once-daily oral regimen.

Investigators at Howard Brown Health in Chicago wanted to study real-world use patterns and HIV seroconversion for F/TAF and F/TDF.

Laura Rusie, ScM Director of Data, Evaluation, and Epidemiology, Howard Brown Health led the study and presented the oral abstract, Comparing Adherence to HIV PrEP Among New, Male PrEP Users Initiating F/TAF vs. F/TDF, at the 

11th International AIDS Society Conference on HIV Science.

“Because of the fairly recent approval of F/TAF, there is a need for real-world contemporaneous data comparing outcomes among users using these two different regimens,” Rusie said in her presentation. “This work aims to be among the first to use real-world claims data to analyze two outcomes: adherence and HIV seroconversions for each regimen.”

They study had a total of 1113 F/TAF users and 1961 F/TDF users who met the criteria. The investigators performed a retrospective analysis of data from medical and pharmacy claims. The study looking at adult males with their first PrEP prescriptions written between October 2019 through January 2020.

According to the findings—using multivariate analysis—the investigators found that at 180 days, F/TAF users had 1.67 higher odds of adherence as compared to F/TDF users. They also noted that adherence odds increased with older populations and those with private insurance.

When looking at seroconversion, rates were not statistically different, but there was a numerical difference. “F/TAF showed a numerically lower incidence of seroconversion at all time points compared to F/TDF,” Rusie explained in her presentation. The differences in seroconversion demonstrated rates of 1.24/100 person-years for F/TAF users, and 1.80/100person-years in F/TDF users.

 spoke with Rusie about her study, insights on upstream barriers to PrEP initiation, and what motivates people to stay engaged in their therapy.

Investigators wanted to study usage of F/TAF vs F/TDF in clinical practice and HIV seroconversion.

Evaluating Adherence of PrEP Therapies

New phase 2A trial data suggest once-monthly pre-exposure prophylaxis (PrEP) islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor, was generally well tolerated and associated with mostly mild adverse events versus placebo in patients at low risk of contracting HIV-1 infection.

The new 24-week data, presented by Merck at the 

 this week, also showed islatravir levels in peripheral blood mononuclear cells (PBMCs) remained above investigators’ pre-specified efficacy pharmacokinetic threshold at both 60 mg and 120 mg doses, 8 weeks following the final trial dose.

In an interview regarding the findings at IAS 2021, study author Sharon Hillier, PhD, director of Reproductive Infectious Disease Research at UPMC Magee-Womens Hospital in Pittsburgh, discussed the implications of a tolerable and potentially efficacious one-month PrEP.

“Bottom line, pretty stellar safety profile for this drug at either concentration,” Hillier said.

Hillier also discussed ongoing phase 3 trial assessment of islatravir for HIV-1 PrEP, the benefit of these findings toward prescriber confidence, and the role of emerging preventive agents in the evolving HIV response capability.

New 24-week findings from Merck highlight the potential of a 1-month PrEP option for low-risk patients.

Islatravir Safe, Tolerable for HIV-1 PrEP in Phase 2A Trial

Earlier this year, the Pew Trusts released a 

 that showed there were only 43 new antibiotics in development. Typically it takes 10 to 15 years from development to approval for antibiotics, but it only takes 2 years to develop bacterial resistance to new antibiotics.

This is compounded by the fact more than 2.8 million antibiotic-resistant infections occur in the United States and at least 35,000 people die as a result according to the US Centers for Disease Control and Prevention’s (CDC) Antibiotic Resistance Threats in the United States report.

While there is certainly a need for new therapies, there are significant barriers for development. With the process taking several years, many smaller companies end up dropping out of development. In addition, the market for reimbursement is low for antibiotics and further disincentivizes pharmaceutical companies from developing them.

The US federal government is looking to create incentives to encourage companies to develop new antibiotics. The US National Action Plan for Combating Antibiotic-Resistant Bacteria directed federal agencies to accelerate a response to antibiotic resistance and take action to expand the ability of our health care system to prevent, identify, and respond to the infection pandemic threat posed by antimicrobial resistance. Part of this plan was to increase and incentivize development of innovative antimicrobial drugs to treat resistant infections.

The Pioneering Antimicrobial Subscriptions to End Up surging Resistance (PASTEUR) Act, is a bipartisan, bicameral piece of legislation aimed to incentivize innovative drug development targeting the most threatening infections, improve the appropriate use of antibiotics, and ensure domestic availability when needed. Initially introduced in Congress by U.S. Senators Michael Bennet (D-Colo.) and Todd Young (R-Ind.) in September of last year, Bennet and Young along with and Representatives Mike Doyle (D-Pa.) and Drew Ferguson (R-Ga.) reintroduced the bill in June.

The prospective bill if passed, would do the following:

Establish a subscription model to encourage innovative antimicrobial drug development aimed at treating drug-resistant infections. This model will be fully delinked, meaning that participating developers would not receive income, as a part of their subscription payments, based on volume or quantity of sales.

Subscription contracts would contain terms and conditions including product availability to individuals on a government health insurance plan, supporting appropriate use, and completion of postmarketing studies. These contracts could be valuated between $750 million and $3 billion.

Build on existing frameworks to improve usage of the CDC National Healthcare Safety Network, the Emerging Infections Program, and other programs to collect and report on antibiotic use and resistance data.

Include transition measures such as smaller subscription contracts to support novel antimicrobial drug developers that need a financial lifeline.

 spoke with Wes Kim, PhD, senior officer 

, Pew Trusts who provided further insights about the Pasteur Act, discussed the economic pull incentives to stimulate antibiotic development, and the role COVID-19 played in the antibiotic market.

The Pasteur Act in Congress is designed to incentivize pharmaceutical companies to develop new antibiotics. 

Offering Market Incentives to Address Antimicrobial Resistance 

When people are considering a newer therapy, they will weigh the potential benefits against their concerns. Barriers to usage can include costs, side effects, frequency of administration, and in some cases, stigma. Sometimes these barriers remain too much for people, and prevents them from beginning a regimen.

 is certainly a therapy that warrants consideration before beginning it. While overall it has seen an increase in usage every year, it has not realized a widespread utilization in candidates who could benefit from it. According to the US Centers for Disease Control and Prevention, as many as 1.1 million Americans could benefit from PrEP, including 175,000 women and 780,000 people of color.

Yet, statistics on usage remains low compared to the prospective benefactors.

, there were only 77,120 PrEP users in the US in 2016. They also found that there was a 73 percent increase year over year in persons using PrEP across the US from 2012 to 2016. Although this would suggest a growing trend in the right direction, its obvious many more people could take advantage of the therapy.

And it does not appear to be an issue of awareness with PrEP. A team of investigators 

 of 202 young, minority men and transgender women to try and gain an understanding as to why some individuals were more likely to take PrEP than others. Findings from the study demonstrated that 98% of the participants were aware of PrEP, but less than 25% were currently taking it.

Additional findings showed that there were racial and ethnic differences in certain factors associated with the use of PrEP. While White participants likelihood of using PrEP increased with age, participants of color were more likely to take the therapy if they were given information by a healthcare provider and if they had positive beliefs about using it.

With the prospective addition of long-acting injectables for PrEP in the near future, having another treatment option that requires less administration may make it is easier to maintain and therefore lead to greater utilization. Investigators associated with Johns Hopkins, Emory’s Rollins School of Public Health, and ViiV Healthcare surveyed the MSM population to gain insights into their attitudes towards the therapy as well as the concerns associated with taking it.

Principal investigator of the survey, S. Wilson Beckham, PhD, MPH, MA, assistant scientist, Department of Health, Behavior and Society, and Department of International Health—Social & Behavioral Sciences, Johns Hopkins Bloomberg School of Public Health, is presenting his study, Variation in Preferences for Long-Acting Injectable PrEP Among US Men who Have Sex with Men: a Latent Class Analysis

The investigators used the the 2019 American Men’s Internet Survey (AMIS). This annual, cross-sectional online survey has been ongoing since 2013, has approximately 10,000 cisgender men ages 15+ living in the US recruited per cycle, and they identify as gay, bisexual, and/or reported sex with men.

They added a few questions geared towards attitudes and preferences about long-acting injectable PrEP.

They matched potential barriers or disutility against each other. For example, they took side effects against another barrier, such as costs, to find out in a series of questions which has greater disutility. “The methodology I used was the discreet choice experiment,” Beckham explained. “It is a quantitative way of measuring preferences and trading off those preferences against each other.”

They then added another layer using a pattern of the participants’ responses with the aid of a computer’s artificial analysis to help identify the men into three classes, which included a cost-conscious class; the side effects class; and the stigma class. These classes categorized the greatest concerns for survey participants.

 spoke to Beckham to learn more about the methodology in their survey, gain further insights into the various classes of men, and understanding the respondents’ concerns about injectables.

Investigators surveyed men who have sex with men (MSM) about long-acting injectable pre-exposure prophylaxis (PrEP) including attitudes towards potentially taking it and barriers to usage.

Understanding PrEP Preferences in a Select Population

Patients with HIV who received treatment from a San Francisco drop-in, incentivized care program for homeless or unstably-housed patients shared diverse feedback on their preferred HIV care model, according to a new study.

 this weekend, did show one interesting consistency among the population, however: telehealth services were not preferred, even during the COVID-19 pandemic.

Presented by study author Elizabeth Imbert, MD, MPH, associate professor at UCSF and clinical lead of the trial’s POP-UP Program at Ward 86, the 115-participant discrete choice experiment provided a detailed yet vital scope of patient perspective in a region where less than 40% of all people with 

 experiencing homelessness or unstable housing have achieved viral suppression.

during IAS 2021, Imbert explained the particular motivations of the trial, which combined patient feedback on care models, physician continuity, telehealth resourcing, and incentive-based care.

“We really wanted to go back and ask patients, ‘How should we change? How should we think about telehealth? Is that going to work for you or not?’” she explained.

The leading take-home message, Imbert said, was as simple as this: HIV care preferences among unstably-house patients differs.

“Some people want a more flexible model, some people want the same doctor,” Imbert explained. “So I think we need to really think about service models that really allow for provider continuity, but also have enough flexibility that people can tailor their preferences among all the other things we provide.”

The lack of telehealth buy-in—at a time when worry for severe COVID-19 risk among patients with HIV was raised, no less—more so spoke to the strength of programs such as Imbert’s in the first place.

“This is really telling that people want in-person care, and even when these big structural things happen like COVID, we need to be able to serve people and do it in a way that they want and will be successful for them,” she said.

Perspective gained from persons treated a real-world clinic may help better inform strategies to treat an HIV population that often struggles with viral suppression and consistent care.