Gina Battaglia, PhD

Clostridioides difficile (C difficile) infection

, particularly in the recurrent setting, is associated with substantial disease and economic burdens for patients and health care systems. Utilizing patient care strategies that minimize infection risk is vital, according to experts who participated in a recent 

 infection (CDI) is “huge.” An estimated 462,100 cases of CDI occurred in the United States in 2017,1 and the economic cost of CDI was estimated to be $5.4 billion overall ($4.7 billion in health care settings) in 2014, according to a decision-analytic model.2 Recurrence is common and can be debilitating for patients, according to 

“I’ve had patients who’ve had recurrent disease, and they’ve [lost] jobs because of the nuisance it causes with the diarrhea they experience,” she said.

Feuerstadt added that although much of the focus is on the vegetative stage, during which the spores germinate to produce toxins that cause symptoms, the pathogen is hardier and more easily spread in the spore phase, because the spores are resistant to gastric acid and alcohol-based hand sanitizers.

“When we swallow the spore phase, it can get through our gastric acid, it gets to our small bowel,” Feuerstadt said. “In the small bowel, there’s a convergence to the vegetative phase where the vegetative phase multiplies, divides, and multiplies some more.”

Feuerstadt added that CDI risk factors include age greater than 65 years; female gender; immunocompromised state such as chronic kidney disease, HIV infection, or inflammatory bowel disease; recent use of antimicrobials, proton pump inhibitors, or histamine blockers; and residence in a skilled nursing facility or prolonged hospital stay. Chopra added that highly virulent toxigenic strains, such as the North American strain that caused outbreaks in the United States and Canada, are also of concern when considering transmission in the hospital or community setting.

 have been identified, although toxin-producing strains are the only ones associated with illness.3 Colonization by toxigenic strains leads to production of toxin A and toxin B in the gut, which leads to the diarrhea associated with CDI.3 Mortality is relatively higher and may exceed 5% with ribotypes 027 and 078, which have been epidemic since 2000, according to 

. He attributed the high mortality rate in part to the fact that the strain tends to infect older and immunocompromised patients, with the highest rates of mortality reported in patients in their 80s and 90s.

, said that the mortality rate increases substantially in patients older than 65 years, with an estimated rate of 10%. Chopra noted that CDI has been labeled as an urgent threat by the Centers for Disease Control and Prevention (CDC) because of the high rate of associated morbidity and mortality. She added that, although the rate of hospital-acquired infections has plateaued in recent years, the increase in community-acquired infection indicates the need for improvement in community stewardship programs.

 spores are ubiquitous in the environment and even are present at low levels in meat, root vegetables, and lettuce, but health care environments are more contaminated with the spores, Gerding said. A news release from the CDC stated that 82% of patients with community-associated CDI had been in an outpatient setting (eg, doctor’s or dentist’s office, chronic dialysis unit, or ambulatory surgery unit) in the 12 weeks prior to receiving a diagnosis of CDI.4 Gerding attributed this risk to the high rate of patients being prescribed antibiotics as well as the high level of contamination of 

 spores also contributes to their ability to spread infection.

“Those spores can live for a significant period of time on many surfaces, even when exposed to sunlight,” he said. “You’ll see some data that say, ‘Alcohol and certain products can kill the spores,’ but they really have to be used properly, [to have] the liquid [sit] on a surface for a significant period of time to have effect. The fact that the spores can be taken home with you on your lab coat and [remain] in your house and on surfaces for 6 months, a year, or longer, certainly puts [individuals] at risk.”

Recurrence of symptomatic CDI is relatively common, difficult to treat effectively, and a cause of significant morbidity and economic costs. Recurrence occurs in 20% to 30% of cases, with higher rates reported with each subsequent episode.5

“If we saw 100 patients with [CDI] and we treated them all…about 25 patients would come back with their first recurrence,” Reilly said. “If we treated those 25 successfully, about 40% of those patients would come back with their second recurrence. And if we treated those patients successfully, about 60% would come back for their third recurrence. So, for every 100 patients we treat, you wind up [with much more than 100 visits], which is the nature of the beast.”

Lodise added that the level of risk varies among antibiotics and increases with longer duration spent in a health care setting. He said that fluoroquinolones and third-generation cephalosporins are among the most commonly used antibiotics and have a higher risk for selecting for CDI compared with other drugs. “One thing I would say with antibiotics is that every day matters,” he said. “Even 1 dose of an antibiotic can put a patient at a greater risk for [CDI] relative to no antibiotics. That risk increases substantially after 3 days of antibiotics.”

He added that for patients who are older and have a high risk of mortality, morbidity, or recurrences, keeping them on an antibiotic without an indication is “often the worst thing you can do” because the risk of CDI is elevated for at least 3 months after taking antibiotics. Through his stewardship efforts, Lodise communicates how important it is to get patients off antibiotics, particularly broad-spectrum antibiotics.

According to Feuerstadt, the burden of disease with recurrent CDI is significant. Physical manifestations include abdominal cramps, diarrhea, dehydration, and syncope related to the frequent loose stools. There also are psychological, adaptation, relational, and productivity effects. He added that these effects are observed in patients with active disease as well as those with a distant history of infection.

“One of the concepts that is very important is to acknowledge for patients is that this is real and that what they’re going through is not just them,” Feuerstadt said. “[Patients] feel stressed about this. They have posttraumatic stress disorder; they feel anxiety or depression. Sometimes they feel [as though] they can’t be the person they were before. Educating ourselves as clinicians about this disease, both the physical manifestations and the emotional manifestations, will make all of us better clinicians and better equipped to approach these individuals and help them get better physically and emotionally.”


Professor of Anesthesiology
Columbia University Irving Medical Center
New York, New York


Professor of Internal Medicine, Division of Infectious Diseases
Wayne State University School of Medicine
Detroit, Michigan


Gastroenterologist, Department of Internal Medicine
Yale New Haven Hospital
New Haven, Connecticut


Research Physician
Edward Hines Jr Veterans Administration Hospital
Chicago, Illinois


Professor
Albany College of Pharmacy and Health Sciences
Albany, New York


Pharmacy Residency Program Director
Clinical Pharmacist Specialist
AtlantiCare Health System
Galloway, New Jersey

Guh AY, Mu Y, Winston LG, et al; Emerging Infections Program Clostridioides difficile Infection Working Group. Trends in U.S. burden of 

. 2020;382(14):1320-1330. doi:10.1056/NEJMoa1910215

Desai K, Gupta SB, Dubberke ER, Prabhu VS, Browne C, Mast TC. Epidemiological and economic burden of 

 in the United States: estimates from a modeling approach. 

. 2016;16:303. doi:10.1186/s12879-016-1610-3

Dayananda P, Wilcox MH. A review of mixed strain 

. 2019;10:692. doi:10.3389/fmicb.2019.00692

Nearly half a million Americans suffered from 

 infections in a single year. News release. Centers for Disease Control and Prevention. Updated March 22, 2017. Accessed January 31, 2021. 

https://www.cdc.gov/media/releases/2015/p0225-clostridium-difficile.html

Cole SA, Stahl TJ. Persistent and recurrent 

. 2015;28(2):65-69. doi:10.1055/s-0035-1547333

Articles

Experts discuss the bacteria’s transmission in the community setting, how to reduce disease and economic burdens, and ways to improve quality of life for patients.

Advances in the Management of C difficile

On September 10, 2020, MJH Life Sciences™ introduced the 

, a partnership with renowned health care thought leaders across multiple medical disciplines. The coalition will present biweekly webinars that give providers resources to improve patient outcomes during the 

 pandemic. The first 5 webinars addressed issues related to influenza and COVID-19, myths and controversies, treatments, vaccines and prophylactic therapies, and long-term physical and psychological effects.

Battling Dual Threats: Influenza and COVID-19 Coverage

, of Columbia University Mailman School of Public Health; 

, of the College of Public Health at the University of Georgia; and 

, of the University of California, Riverside, participated in this webinar on September 15, 2020.

COVID-19 and Influenza: A Tale of 2 Viral Pathogens

Rasmussen noted that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses have distinct taxonomy, genomics, and evolutionary origin, as well as modes of entry into and replication inside the cell. In addition, the higher mutation rate of the influenza virus is related to its ability to reassort its genome. She added that SARS-CoV-2 appears to have a stronger effect on the central nervous system and gastrointestinal tract and infects the cardiovascular system directly. Pathogenic strains of the influenza virus, on the other hand, affect the cardiovascular system through the increased entry of macrophages. Rasmussen also noted that the differential pattern of pathway induction in the immune response suggests that these viruses induce distinct host responses. She added that case reports show coinfection of SARS-CoV-2 and influenza does occur, but the effect on disease severity is unclear. “We need more data from a broader range of patients,” she concluded.

Population-level Patterns of COVID-19 and Influenza: What Should We Expect?

Handel said that behavior changes and the nonpharmaceutical interventions (NPIs) implemented for COVID-19 have likely had an effect on the influenza rate. He pointed to data showing that rates in the 2019-2020 season were lower than expected in multiple countries which, along with lower test positivity rates in China and a minimal number of influenza-related hospitalizations in Australia, suggests a true decrease in influenza cases (versus reduced reporting of cases). He concluded that key factors that will dictate the interaction between COVID-19 and influenza in the long-term include the effects of a COVID-19 vaccine on influenza vaccine uptake, NPIs, and individual behavior patterns; development of a universal flu vaccine; and COVID-19 treatments.

Morrison noted that although several COVID-19 vaccines are currently in phase 3 trials, their rapid development has contributed in part to high levels of vaccine hesitancy among the general public. She added that this skepticism has prompted vaccine developers to make a historic pledge stating that they will uphold the integrity of the scientific process, and ensure that regulatory filings and approvals are up to par and no corners are being cut. Morrison cited the example of AstraZeneca putting their trial on hold when a participant developed an illness that may have been related to the vaccine. She concluded that educating the public about the perceived threat of COVID-19 and the effectiveness and safety of the vaccines that become available are key to fighting vaccine hesitancy.

Fact or Fiction? COVID-19 Myths and Controversies

 infectious disease epidemiologist and infection preventionist in Phoenix, Arizona; 

 of the National Institute of Allergy and Infectious Diseases, National Institutes of Health; and 

, addressed common COVID-19 myths and controversies in a COVID-19 Coalition webinar on September 29, 2020.

MYTH 1: “SARS-CoV-2 is totally airborne”

Rasmussen said that SARS-CoV-2 is primarily transmitted through short-range respiratory droplets or aerosols between individuals in close contact for long periods of time. “The word ‘airborne’ is often misleading because a lot of times people think of long-range transmission,” she said.

Ricotta added, “We need to be clearer in the way that we’re communicating this, and I think that’s where some of the confusion has come in.” However, both panelists agreed that these discrepancies in definition do not affect current recommendations for preventing transmission (such as mask usage).

MYTH 2: “Herd immunity is achievable through natural infection”

Ricotta said that herd immunity through natural infection would likely require 40% to 70% of the population to be infected and have sustained immunity. In addition, as not all the long-term effects of COVID-19 are known, many people would be put at risk with this strategy. Rasmussen added that global herd immunity through natural infection has not been achieved for any pathogen and does not keep the pathogen out of the environment in the long-term.

MYTH 3: “We can’t trust data quality”

Ricotta said that the data source, consistency in data reporting, interruptions in data collection, and consistency in criteria for positivity can affect data. “It’s not necessarily the quality of data. You just have to be really careful when you’re working with and interpreting them,” she said.

Rasmussen added that communicating with the public about the appropriate use of mathematical models has been a “tremendous challenge.” They’re only as good as the information that goes into building them at the time, and that’s constantly changing.”

MYTH 4: “There is no asymptomatic transmission”

Rasmussen said that distinguishing asymptomatic from presymptomatic transmission and estimating the prevalence of asymptomatic cases, which is a substantial source of transmission, has been difficult. This is because most asymptomatic cases are based on self-reported data, symptoms can develop after a positive test, and people may not recognize that mild, nonspecific symptoms are related to COVID-19.

MYTH 5: “Any SARS-CoV-2 vaccine won’t be safe”

Rasmussen said the purpose of clinical trials is to ensure vaccine safety and efficacy. Ricotta added that postmarket evaluation of vaccines is performed and possible vaccine-associated events are reported in a tracking system. Although vaccines have risks, Ricotta said they are often considered acceptable relative to the risks associated with the disease.

MYTH 6: “Young people can’t get sick”

According to Ricotta, although young patients often have fewer symptoms than older patients, some require hospitalization and have had blood clots, strokes, and myocarditis. Rasmussen added that symptoms in children can be vague and difficult to associate with COVID-19, and she and Popescu pointed out that cases in children may be underreported.

The immune system response to SARS-CoV-2 immunoglobulin G (IgG) is consistent with that of other viruses, Rasmussen said. Memory immune cells likely persist, even if IgG decreases to undetectable levels, and assumptions about long-term immunity cannot be made based on antibody levels.

MYTH 8: “Hydroxychloroquine is a miracle drug”

Rasmussen said that none of the high-quality randomized controlled trials and observational studies show a clinical benefit for prophylaxis or treatment, and the drug can cause ocular problems or cardiac arrhythmias.

MYTH 9: “COVID-19 is no worse than the flu”

Although both viruses affect the respiratory tract and have similar modes of transmission, comparing COVID-19 to influenza is “like comparing apples to oranges, ” Ricotta said. Getting tested for both viruses is important to guide treatment. Rasmussen added that aside from the fundamental differences in the viruses, the 2 diseases should not be compared because of the differences in treatment and vaccination recommendations.

Navigating the COVID-19 Treatment Landscape

This October 13, 2020, webinar included moderator 

, of the University of Michigan College of Pharmacy; 

, of Temple University School of Pharmacy.

Davis said that although updated results showed differences in mortality at day 15, illness severity, hospital stay, and time to recovery are also important measures to consider when deciding whether to give remdesivir. Additionally, the guidelines for use from the National Institutes of Health and the Infectious Diseases Society of America were based on the drug’s limited availability early in the pandemic. The increase in availability and advent of new therapies since then may change when and which patients receive the drug, according to Davis.

The panelists stated that a wide range of patients, including those with minimal need for supplemental oxygen, would likely benefit from dexamethasone. Gallagher cautioned against making assumptions about when a patient is in the “inflammatory phase” of the disease, given that knowledge about its clinical course is continuing to evolve. Moving forward, he recommended focusing on clinical data when assessing clinical benefit from dexamethasone.

Although an emergency use authorization (EUA) was given, Gallagher said the data from the nonrandomized Mayo Clinic Expanded Access Program are difficult to interpret. Further, he remarked that the benefits appear to be primarily in patients who have not produced their own antibodies to SARS-CoV-2. Davis noted that the primary intention of the program was to improve access for patients and that it was not designed as a clinical trial. Pogue added that convalescent plasma may have lower levels of antibodies than the levels the patient has produced.

Although the data published in press releases appear promising, Davis said such data from pharmaceutical companies is insufficient for rational decision-making in the clinic. When companies apply for an EUA, closer communication with the FDA can expedite additional treatment options in a pandemic, but a completed clinical trial is necessary for an agent’s widespread use in the clinical setting, she continued.

“EUA is a tool for a health emergency,” said Davis. “It is not a replacement for the normal drug approval process.”

Gallagher added that monoclonal antibodies may predict progression in patients who are readmitted to the hospital but the logistical challenges, such as the need for intravenous infusion, will likely limit their overall impact on reducing transmission and improving outcomes.

Race for a Vaccine: The Latest Updates in COVID-19 Prevention

 CEO of PAX Therapeutics and chairman of the board of the International Society for Vaccines; 

, head of monoclonal antibody clinical testing in the COVID-19 Prevention Trials Network; and 

, head of vaccine testing in the COVID-19 Prevention Trials Network, participated in this webinar, held October 27, 2020.

According to Cohen, key advantages of monoclonal antibody therapy include the ability to offer immediate protection to exposed or unvaccinated individuals in high-risk settings, provide an option for patients unlikely to respond to or who are allergic to a vaccine, and stop viral replication and disease progression. Several phase 3 trials are ongoing for monoclonal antibody therapies, including one (NCT04452318) that is evaluating the efficacy of REGN10933 + REGN10987 (which prevents the receptor binding domain of the spike protein from reaching the ACE2 receptor) for preventing infection in the household contacts of individuals who test positive for COVID-19. Another is the BLAZE-2 trial (NCT04497987), which is investigating the antibody LY-CoV555 for preventing infection in residents and staff of skilled nursing and assisted living facilities.

Corey said that several features of SARS-CoV-2, including its relatively high infection cure rate, mutation rate of 2 base pairs per month with little variation in neutralizing areas of the spike protein, and recent evidence of past infection protecting against acquisition, have made COVID-19 vaccine development more straightforward than that for HIV.

The conceptual framework for COVID-19 vaccine development involves developing multiple vaccine platforms (protein-, viral vector–, and RNA-based) and having a coordinated effort from the US government to involve global vaccine manufacturing companies, said Corey. He also emphasized the importance of having a common data safety monitoring board for these efficacy trials using different vaccine platforms, with decisions for a given candidate based on the context of the other trials.

According to Corey, the main goal of these trials is to evaluate each candidate vaccine for safety and efficacy for reducing COVID-19 disease, with approximately 30,000 individuals enrolled per trial; measure 150 disease end points; enroll Black, Latinx, and tribal communities; and evaluate vaccines in epidemiologic settings of individuals at greatest risk for complications based on comorbidities, age, and race.

“COVID-19 vaccines provide the leading approach for changing the societal and medical complications of the COVID-19 pandemic. A vaccine that protects from medically complicated COVID-19 disease would provide enormous help in relieving the uncertainty that accompanies work, travel, and gatherings with family, friends, and community,” said Corey.

Thinking Long-Term: COVID-19’s Clinical Consequences and Mental Health Effects

, of Feinberg School of Medicine at Northwestern University; 

, of Emory School of Medicine and Grady Health System; and 

, executive director of the Center for Childhood Resilience, participated in this November 12, 2020, webinar.

Tan pointed out that although most children and infants generally present with mild or no symptoms, they may have persistent and long-term symptoms even if they have mild illness and no underlying medical conditions. Multisystem inflammatory syndrome in children is the most serious and can result in long-term cardiac, neurologic, and gastrointestinal problems.

Long-Term Health Consequences of Covid-19

Del Rio estimated that 10% to 15% of patients do not recover quickly based on findings from the COVID Symptom Study, and the persistence of symptoms is independent of age, comorbidity burden, and severity of acute illness. He added that cardiac injury, myocarditis, arrhythmias, cardiogenic shock, and thromboembolic disease may occur in the acute phase. These can lead to myocardial fibrosis or scarring, arrhythmias with cardiac arrest outside the hospital setting, and cardiomyopathy in the postacute phase. Pneumonia, acute respiratory distress syndrome, and hypoxic respiratory failure can occur during the acute phase and be followed by restrictive lung disease in the postacute setting. In addition, major mood swings and “brain fog” can persist for several months. Del Rio added that renal function may also be compromised long-term, with persistent kidney dysfunction or requirement for dialysis even in patients who did not require renal replacement therapy during hospitalization. Finally, he cited emotional and behavioral concerns, including feelings of isolation and loneliness, a sense of hopelessness, and ongoing psychological effects, and identified the need for an integrated research agenda to conduct observational studies and randomized trials and a multidisciplinary approach to treatment in post–COVID-19 clinics.

The Uninvited Guest: Promoting Mental Health & Wellness During COVID-19

Cicchetti said that issues related to the COVID-19 pandemic, racism, and economic downturn in 2020 have contributed to multiple layers of stress in many individuals. Ongoing mental health challenges for many individuals include a sense of inequity, structural racism, heightened exposure to stress and trauma, social isolation and disconnection, limited access to community programs and support, changes to routine and structure, barriers to accessing health care and other services, and educational disruptions for children.

Cicchetti emphasized the importance of providers addressing stress directly with clients using tools such as Stoddard and Kaufman’s Coronavirus Impact Scale and the UCLA Brief COVID-19 Screen for Child/Adolescent PTSD. She recommended that parents respond to their children using principles of trauma-informed care, including creating a safe environment, building relationships and connectedness, and supporting and teaching emotional regulation. She added that the majority of children will do well, and often look to parents for coping strategies and leadership during times of crisis. Create a sense of predictability and establish routines to enhance children’s safety and security, she suggested, as well as providing them with love and support. Additionally, allowing them to ask questions, supporting their emotional regulation, and letting them figure out how to support themselves with self-care activities will help them reduce stress, cope with challenges, and enhance their sense of well-being.

The biweekly webinars hosted by renowned health care thought leaders provide resources to improve patient outcomes during COVID-19. Here's a recap of the first 5 discussions.

Lessons Learned from the COVID-19 Coalition


Professor of Medicine, Division of Infectious Diseases
University of North Carolina School of Medicine
Chapel Hill, NC


Associate Professor of Pediatric and Adult Infectious Diseases
Johns Hopkins University School of Medicine
Baltimore, MD


Professor of Medicine
University of Pennsylvania Perelman School of Medicine
Philadelphia, PA


Associate Professor of Medicine, Division of Infectious Diseases
Emory University School of Medicine
Atlanta, GA


Infectious Disease Epidemiologist
Associate Professor, Department of Population Medicine
Harvard Medical School and Harvard Pilgrim Health Care Institute
Boston, MA

New antiretroviral drugs with unique mechanisms of action and delivery provide promising options for treatment and pre-exposure prophylaxis (PrEP) of HIV infection and may improve adherence in certain subgroups of individuals. However, the development of an effective vaccine remains elusive, according to experts who participated in a recent 

Fostemsavir (formerly BMS-663068/GSK3684934), a prodrug whose active metabolite (temsavir) is a first-in-class attachment inhibitor that binds directly to the viral envelope glycoprotein 120 near the CD4+ binding site,

 was approved by the FDA on July 2, 2020, for adults living with HIV who have tried multiple HIV medications and whose infection cannot be treated with other therapies because of resistance, intolerance, or safety reasons.

 This approval was based largely on results from a phase 3 trial, which showed a virologic response (HIV-1 RNA <40 copies/mL) at week 48 in 54% of patients with heavily pretreated, multidrug-resistant HIV infection who received fostemsavir plus optimized background therapy.

, said that its oral dosing is advantageous over ibalizumab, which is dosed intravenously, although he said that fostemsavir will probably be limited for patients with few or no treatment options.

, added that long-acting injectable and oral agents, capsid inhibitors, and monoclonal antibodies are also being studied in the HIV space, as are alternative delivery approaches, such as subcutaneous injections, pumps, implants, and patches. However, she pointed out that access to and the cost of these novel options will be key issues moving forward, particularly when currently available oral agents are highly effective for suppressing HIV viral load in the majority of cases.

“The discussions we’ll have to have on how and who and where are going to be very important,” said Agwu. “It doesn’t mean we shouldn’t have those discussions because for the people who are living with HIV, these are maybe life-saving, game-changing remedies for them.”

Long-Acting Injectable Therapies to Treat HIV

The panelists discussed potential uses and challenges with the long-acting injectable therapy containing cabotegravir (an HIV-1 integrase strand-transfer inhibitor) and rilpivirine (a non-nucleoside reverse-transcriptase inhibitor), which is injected in 2-mL doses in the gluteus medius every 4 weeks for the maintenance of virologic suppression in patients who are initiating or transitioning therapy. Although the FDA declined to approve the combination in December 2019 due to concerns related to chemistry manufacturing and controls, the drug manufacturer (ViiV Healthcare) stated that no related safety issues have been reported and the safety profile of the products has not changed. ViiV Healthcare submitted another new drug application that was accepted in April 2020.

, said that a benefit of long-acting injectable dosing is that it may help reduce the internalized stigma for many individuals living with HIV who take a daily oral medication. “It’s a constant reminder when you have that pill bottle on your bathroom stand that says, ‘I am HIV positive,’” she noted.

However, the panelists pointed out potential drawbacks with long-acting injectables, such as the risk for drug resistance in patients who miss injections and the possible need to modify the clinic set-up to ensure availability of nursing staff when patients are receiving injections.

“Although there may be some adherence problems that get solved by the injections, I think that there are other adherence risks that get created,” said 

. “It’ll be more incumbent upon us as providers to ensure that our patients are coming in at the appropriate frequency, and we may need to modify our practices.”

Long-Acting Injectables as Pre-Exposure Prophylaxis

Long-acting injectable therapy with cabotegravir may provide a discreet option for PrEP that does not require daily dosing, according to a recent interim analysis of the phase 2b/3 HPTN 083 trial (NCT02720094).

 The interim results from the trial showed that cabotegravir injection every 8 weeks was superior to daily oral emtricitabine/tenofovir (Truvada) for preventing HIV acquisition in cisgender men who have sex with men and transgender women who have sex with men.

To have population-level effectiveness, long-acting injectable PrEP needs to cater to a population of individuals who are eligible for and interested in receiving it but are not interested in daily oral PrEP, according to 

. “If the only people who are interested in long-acting PrEP are people who are already taking daily PrEP…it’s not going to have any population-level effectiveness,” she said.

Marcus added that identifying individual barriers to receiving oral PrEP is important to assess whether long-acting injectable PrEP is appropriate for them, noting that it would be more likely to benefit an individual who forgets to take daily medications than one who has difficulty with coming into the clinic.

“If their [issue is] that they don’t want to be coming into the clinic every 3 months, long-acting injectables may not help them,” she said. “They may have to come in even more.”

Other individuals who may be good candidates for long-acting injectable PrEP include those for whom having oral medication may put them at risk for bodily or emotional harm, such as people in unequal power relationships, commercial sex work, or homeless living situations, said Eron and Marcus. Individuals who use injectable drugs or are on methadone maintenance may also be good candidates for PrEP if they come in frequently for syringe changes, said Marcus.

Agwu added that long-acting injectable PrEP could also expand the options in the armamentarium for a given patient at different times of their life.

“If a patient has to go abroad for 2 months, maybe that’s the time to get your shot,” she said. “You don’t have to worry about taking your pills to Morocco.”

She said that further work is needed to optimize system and administration issues and improve practices for delivering long-acting injectable therapy in the clinic. Eron concluded that further research to ensure the efficacy and demedicalization of PrEP is important to improve uptake, as the perception that PrEP care is more intensive than HIV care continues to persist among individuals who are eligible for PrEP.

Preventative and Therapeutic HIV Vaccines

Although the phase 2b/3 HVTN702 trial (NCT02968849), which studied the RV144 Thai vaccine regimen for the prevention of HIV infection in South Africa, was recently discontinued because of a lack of efficacy, Kelley said that this outcome does not mark the end of the journey for finding an effective vaccine, which will be the key to ending the HIV epidemic.

“There’s still more work to be done and no reason to lose hope,” she said. “We’re thinking about monoclonal antibodies and long-acting antiretrovirals in place of a traditional vaccine.”

Kelley said that researchers are getting closer to identifying what the immune system needs to do to protect itself from HIV infection. “If these neutralizing antibodies are the key, how do we make our human immune system create those neutralizing antibodies? ….That’s been extremely difficult to do,” she said. “We can make the antibodies outside the person, but we can’t make the person produce the antibodies. This is the biggest barrier right now.”

Frank added that therapeutic vaccines are also being investigated as a strategy for curing HIV, with “cure” defined “in the context of doing something other than requiring people to take regular antiretroviral therapy to control the virus replication.” Specifically, the goal of a therapeutic vaccine is to improve the individual’s immune response against the infection to enable the withdrawal of antiretroviral therapy and promote an improved immune response to control virus replication, said Frank. He concluded that although therapy and prevention continue to improve, the absence of an effective vaccine and a cure are “the real vacuum” in HIV prevention and treatment, respectively.

Advice for Physicians Treating Patients with HIV

At the conclusion of the exchange, the panelists discussed tips for physicians in the screening, diagnosis, and treatment of patients living with HIV. Agwu stressed the importance of asking patients about risk factors for HIV, including sexual activity, and testing and offering PrEP for patients at high risk. Kelley added that in addition to routine discussions about sexual health, maintaining consistency in the treatment of each patient and identifying other issues that are common to those living with HIV, such as other sexually transmitted infections, is important.

Marcus added that discussing sexual health in an open-ended, nonjudgmental, patient-centered way is important for optimal communication with patients and that communicating the U = U (undetectable = untransmissible) message can be “transformative” for them.

Frank concluded that although undetectable viral load is often the primary focus of antiretroviral therapy, providers should also consider additional factors, such as comorbid conditions, when optimizing HIV therapy and managing overall care for patients.

“It’s important that we remind our patients that they may have other medical conditions, or they may develop other medical conditions, and those medical conditions may pose as great a risk, if not a bigger risk, than their HIV disease,” said Frank. “I have many patients with uncontrolled hypertension and uncontrolled diabetes and lipids that are high. I tell them that they’re going to die of a heart attack or a stroke or be on dialysis long before they ever get a complication of their HIV. Dying of a heart attack with an undetectable viral load isn’t my goal of their treatment. It’s not just about their HIV.”

1. Langley DR, Kimura SR, Sivaprakasam P, et al. Homology models of the HIV-1 attachment inhibitor BMS-626529 bound to gp120 suggest a unique mechanism of action. 

. 2015; 83(2):331-350. doi:10.1002/prot.24726

2. FDA approves new HIV treatment for patients with limited treatment options. Press release. FDA. July 2, 2020. Accessed October 13, 2020. 

https://www.fda.gov/news-events/press-announcements/fda-approves-new-hiv-treatment-patients-limited-treatment-options

3. Kozal M, Aberg J, Pialoux G, et al; BRIGHTE Trial Team. Fostemsavir in adults with multidrug-resistant HIV-1 infection. 

. 2020;382(13):1232-1243. doi:10.1056/NEJMoa1902493

4. Long-acting injectable form of HIV prevention outperforms daily pill in NIH study. News release. National Institutes of Health. July 7, 2020. Accessed October 13, 2020. 

https://www.nih.gov/news-events/news-releases/long-acting-injectable-form-hiv-prevention-outperforms-daily-pill-nih-study

An expert panel discussion around long-acting injectables' role in both preventing and treating HIV.

Emerging Options for Treatment and Prevention of HIV Infection

Although the overall incidence rate of HIV infection has declined slightly in recent years, increases in the incidence in certain subgroups emphasize the importance of early diagnosis, risk-based screening, and preexposure prophylaxis (PrEP) for individuals at high risk for infection, according to panelists who participated in a 

Burden of HIV in the United States and Associated Symptoms

According to a CDC estimate, approximately 1.2 million people 13 years and older in the United States were living with HIV in 2018, with nearly 38,000 new infections that year.

 While the overall incidence rate decreased by 11% from 2010 to 2017, 

, pointed out that rates of new diagnoses are increasing in certain subgroups, notably Hispanic/Latino, Asian, and American Indian/Alaska Native men who have sex with men (MSM).

 Data from the CDC’s HIV Surveillance Report also showed increases in incidence in the 15- to 19-, 25- to 29-, and 30- to 34-year-old age groups.

“Unfortunately, young people seem to account for about 25% of new infections,” said 

. “We’re not really making a dent in that.”

 added that the HIV epidemic has shifted to the southeastern United States, with more than half of new US cases occurring in that region in 2017.

 “There [are] many sociological and political reasons for that,” he said. “It’s really important for us to be aware of and to consider [when] making public health decisions in this country.”

Agwu said that many of her patients report having a flu-like illness prior to diagnosis, which may include fever, chills, muscle aches, and rash. She added that identification and intervention in the early stages is particularly important for preventing transmission because the viral load is high then.

“They present with the ‘flu,’ but it’s a viral illness, and it’s the acute presentation of HIV,” Agwu said. “Often they seek medical care and are treated for the flu, or they’re sent home with symptomatic management, and that’s when they actually could have been tested and diagnosed with HIV. In these cases, it’s an opportunity and important for us to recognize that people can present like that.”

Frank added that he has observed a recent increase in known acute infections in Philadelphia because of the improved methodologies to perform rapid testing on individuals coming into the emergency department. “We’ve helped our [emergency department] faculty become a little more sensitive to that diagnosis,” he said.

Agwu, who frequently treats patients in the later stages of disease, said that the patients she sees may be asymptomatic; report nonspecific symptoms like sore lymph nodes, fatigue, rashes, yeast infections, and night sweats; or have signs of end-stage disease, such as a CD4 count less than 200 cells/mm

“There are some deficits in our health care system where the system is not engaged, so we really do see the range [of presentations],” Agwu said.

, added that many patients who are diagnosed in the late stages had touched the health care system multiple times over the course of their disease but were not tested for HIV.

“There were missed opportunities for diagnosis where we could have intervened early on and preserved their health, as well as reduced their risk of transmission to [sexual] partners,” Kelley said.

Screening Recommendations for HIV and Risk Stratification

The United States Preventive Services Task Force (USPSTF) recommends that all individuals aged between 15 and 65 years should be tested for HIV at least once in their life; pregnant women and individuals younger than 15 years and older than 65 years who are at high risk for infection should also be tested.

 Although the USPSTF did not have sufficient evidence to establish optimal screening intervals, they stated that repeat screening is reasonable for individuals at increased risk for HIV infection, including sexually active MSM and individuals who have a sexual partner living with HIV, use injectable drugs, have transactional sex or perform commercial sex work, or have at least 1 new sexual partner with unknown HIV status since their last HIV test.

 Frank added that pregnant women who have been tested earlier and may have been exposed to HIV should be tested again in the third trimester because a woman with acute infection is at high risk for transmitting the infection to her newborn.

However, identifying high-risk individuals in clinical practice remains a challenge, according to Marcus. Although some risk assessment tools are available, she pointed out that the tool is primarily designed for MSM.

“A provider already has to know that a patient was in that risk group before they’re going to use one of these tools,” said Marcus. “They’re hard to use in a busy clinical practice, and they also underestimate HIV risk in black men who have sex with men. HIV risk for that community is much more driven by network factors.”

The panelists also discussed the importance of discussing sexual activity and behaviors with patients, a topic often not addressed in clinical practice.

“There are studies that showed the average provider, even the [provider who specializes in caring for] adolescents, spends only 30 seconds talking to adolescents about sex,” said Agwu. “Imagine what’s happening in [terms of discussing sex with] the group of people aged over 55 years. Some physicians and patients may be uncomfortable, and we may not even bring it up. Essentially, we have a whole problem talking about sex.”

PrEP Therapy for High-Risk HIV Candidates

Evaluation of high-risk behaviors is also important to identify whether a patient is a good candidate for PrEP, but asking patients, particularly older ones, about their behaviors can be challenging, according to Frank.

“Older folks are less likely to be asked these questions because assumptions are being made,” said Frank. “You can preface the questions by saying, ‘I ask all my patients these questions.’ So that already means, ‘I’m not asking you because I’m worried about you. I ask all my patients these questions. Are you in or have been in a sexual relationship? Is it with a man? Is it with a woman? Is it with men and women?’ It’s not hard to ask these questions in 30 seconds and receive a lot of information.”

According to the USPSTF and CDC, candidates for PrEP include sexually active MSM who have a partner living with HIV, use condoms inconsistently during anal sex, or have had a sexually transmitted infection (STI) within the past 6 months; heterosexual men and women who have a sexual partner living with HIV, use condoms inconsistently with a high-risk partner whose HIV status is unknown, or have had an STI within the past 6 months; and individuals who inject drugs using shared equipment or are at high risk for sexual acquisition of HIV.

, and the panelists also acknowledged that women often underestimate their risk for contracting HIV.

The CDC says a risk factor for women “is having sex with a high-risk partner,” said Agwu. “If you ask the question like that, of course they’re going to underestimate their risk. If you’re living in a high-risk zip code and you say, ‘Are you having sex with a high-risk partner?’ [the patient will likely answer,] ‘No, I have had 1 partner. No, I’m not.’ However, just living in that zip code, your partner is at higher risk of obtaining HIV. We have to think about how we ask those questions and routinize how we offer treatment, offer testing, and then offer PrEP.”

Kelley agreed that knowing the local epidemiology is also important to consider when assessing a patient’s risk. “Are you in a place where there is high prevalence and new infections that are still turning up, like many places in the Southeast? Or are you in a place where you know there’s maybe not a lot of transmission ongoing?”

Safety Profiles of FDA-Approved PrEP Agents

The 2 combinations approved by the FDA for PrEP are tenofovir disoproxil fumarate-emtricitabine (TDF-FTC; Truvada) and tenofovir alafenamide-emtricitabine (TAF-FTC; Descovy). Frank said that the newer TAF-FTC, Descovy, is as effective and slightly safer than TDF-FTC; it has lower renal toxicity and causes less of a decrease in bone mineral density. He emphasized that PrEP is very effective when people adhere to taking it, but he cautioned that women may need to have higher rates of adherence than men because of the differences in how the drugs enter the tissues and the drugs’ concentrations in mucosal tissues, where patients are most likely to be exposed.

Marcus added that although the newer TAF-FTC is thought to be safer, it is not approved for women at risk for HIV through receptive vaginal sex because it has been evaluated only in MSM and a small number of transsexual women. She added that adverse effects have been observed with TAF-FTC, including increased cholesterol and weight gain, but that both drugs are generally very safe with low rates of discontinuation.

Because of the relative safety of both regimens, Marcus concluded that cost may be a more important consideration when choosing a PrEP regimen, as a generic version of TDF-FTC will be available later in 2020 that could save tens of thousands of dollars. “The cost issue is really relevant here,” said Marcus. “It could make a huge difference once the cost begins to go down on generics.”

1. Statistics overview: HIV surveillance report. CDC. Reviewed June 8, 2020. Accessed June 10, 2020. 

https://www.cdc.gov/hiv/statistics/overview/index.html

2. HIV in the United States and dependent areas. CDC. Reviewed June 10, 2020. Accessed June 10, 2020. 

https://www.cdc.gov/hiv/statistics/overview/ataglance.html

3. HIV surveillance report, volume 30: diagnoses of HIV infection in the United States and dependent areas, 2018 (preliminary). CDC. November 2019. Accessed June 10, 2020. 

https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-report-2018-preliminary-vol-30.pdf

4. HIV in the United States by region. CDC. Updated October 30, 2019. Accessed June 10, 2020. 

https://www.cdc.gov/hiv/statistics/overview/geographicdistribution.html

5. US Preventive Services Task Force; Owens DK, Davidson KW, Krist AH, et al. Screening for HIV infection: US Preventive Services Task Force recommendation statement. 

Although overall incidence rate has declined slightly in recent years, increases in the incidence in certain subgroups emphasize the importance of early diagnosis, risk-based screening, and PrEP for at-risk individuals.