A quarter of people with diabetes develop foot ulcers, which are slow to heal due to hypoxic conditions in the wound from impaired blood vessels and increased inflammation. These wounds can become chronic, leading to poor quality of life and possibly amputation.
Jianjun Guan, professor of mechanical engineering and materials science at the McKelvey School of Engineering at Washington University in St. Louis, has developed a hydrogel that delivers oxygen to a wound and decreases inflammation, helps to remodel tissue and speeds up healing. The results are published in Science Advances.
Prof Guan’s new hydrogel uses microspheres to gradually release oxygen to interact with the cells by means of an enzyme coating that converts the microsphere’s contents into oxygen. In this way, the hydrogel delivers oxygen over two weeks, reducing inflammation and promoting healing. “The oxygen has two roles: one, to improve skin cell survival under the low-oxygen condition of the diabetic wound; and two, oxygen can stimulate the skin cells to produce growth factors necessary for wound repair,” Prof Guan said.
An article in Science explores the evidence for the animal origin of COVID, which was first detected in December 2019, but inferred to be present in Hubei province, China, for about a month beforehand.
The current COVID epidemic can be better understood by examining the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak which began in 2002. Investigations later found that horseshoe bats (Rhinolophus) in China harboured related coronaviruses. It was inferred that a sarbecovirus circulating in horseshoe bats seeded the progenitor of SARS-CoV in an intermediate animal host, most probably civet cats Although other possible intermediate hosts for SARS-CoV were identified, it is a population of civet cats within markets that appear to have acted as the conduits of transmission to humans from the horseshoe bat reservoir of SARS-CoV. Presumably a captive civet cat initially became infected by direct contact with bats or was infected before capture.
SARS-CoV-2 first emerged in Wuhan city, over 1500 km from the closest known naturally occurring sarbecovirus collected from horseshoe bats in Yunnan province. Coronaviruses genetically close to SARS-CoV-2 are circulating in horseshoe bats with wide geographic ranges indicate that the singular focus on Yunnan is misplaced. Confirming this assertion, the evolutionarily closest bat sarbecoviruses are estimated to share a common ancestor with SARS-CoV-2 at least 40 years ago, showing that these Yunnan-collected viruses are highly divergent from the SARS-CoV-2 progenitor.
Though the virus may have jumped to humans from direct horseshoe bat–to–human contact, a known risk for SARSr-CoVs, the first detected SARS-CoV-2 cases in December 2019 are associated with Wuhan wet markets. This is consistent with multiple animal-market–associated spillover events in November and December (9). It is currently not possible to be certain of the animal source of SARS-CoV-2, but it is notable that live animals, including civet cats, foxes, minks, and raccoon dogs, all susceptible to sarbecoviruses, were for sale in Wuhan markets, including the Huanan market (identified as an epicenter of the outbreak in Wuhan) throughout 2019.
Together, this suggests a central role for SARSr-CoV–susceptible live intermediate host animals as the primary source of the SARS-CoV-2 progenitor that humans were exposed to, as was the case with the origin of SARS.
Spillover events are not so rare, indicated by evidence of SARSr-CoV–specific antibodies in people living in rural areas, and even higher rates recorded in people living near bat caves. When exposed a densely packed human population, such as in Wuhan city, these spillover events have a much higher chance of resulting in substantial onward spread
Interestingly, the proximity of humans to wildlife may have been increased by demand for alternative meat sources caused by reduced availability of pork in 2019. This was caused by the African swine fever virus (ASFV) pandemic, which led to ∼150 million pigs being culled in China, resulting in a pork supply reduction of ∼11.5 million tonnes in 2019, and from which the country is still recovering. Increased use of cold-chain logistics in the wake of the ASFV pandemic means that frozen animal carcasses carrying SARS-CoV-2 may have been brought from much farther afield.
Once crossed over, SARS-CoV-2 readily established itself in humans by being a generalist, as opposed to being specialised for humans. Ironically, since humans are now the largest reservoir of the virus, animals in contact with humans are at risk of virus spillover. The article authors closed by stressing the need for much greater viral surveillance to spot emerging threats, as current coverage is extremely spotty.
Just as the European Society of Cardiology (ESC) unveiled their new guidelines for the treatment of heart failure, along came some data that the guideline’s authors hint will cause the work to be revised.
The guidelines, which appear in the European Heart Journal, state that so far, there is no treatment shown to reduce mortality and morbidity in patients with heart failure with preserved ejection fraction, however there are positive results from the EMPEROR-Preserved study showing that treatment with empagliflozin robustly reduced hospitalisation risk.
“Every guideline we write is out of date a few days after it’s published. I’m, of course, exaggerating a little bit, but guidelines are dynamic documents. They represent what we know at the time that they’re written and then new information comes out and they have to be updated, and that takes time,” Milton Packer, MD, of Baylor University Medical Center in Dallas, told MedPage Today.
“It’s a process, and we all understand that process; there is no real concept of finality here. We do the best we can with the data we have. And so these guidelines coming won’t represent the results of the EMPEROR-Preserved trial, but the next one will,” Dr Packer added.
Carlos Aguiar, MD, of Hospital Santa Cruz in Lisbon, agreed: “We also know that these new indications do need to go through the regulatory authorities, so it does take some time for the whole process to be concluded.”
“We do need to wait for those approvals also from the regulatory agencies in their reviews for physicians to be able to implement this in clinical practice,” he told MedPage Today.
However, the writers of the 2021 guideline did tweak the comprehensive algorithm for the treatment of heart failure, the highlights of which include:
Right heart catheterisation should be considered in patients in whom heart failure is thought to be due to constrictive pericarditis, restrictive cardiomyopathy, congenital heart disease, and high-output states. It may be considered in selected patients with heart failure with preserved left ventricular ejection fraction (LVEF) to confirm the diagnosis.
In patients with chronic heart failure with reduced LVEF, dapagliflozin (Farxiga) or empagliflozin are recommended to reduce hospitalisation and mortality risk. As a Class I recommendation, it is based on evidence gleaned from randomised clinical trials.
Vericiguat (Verquvo) may be considered in patients with New York Heart Association (NYHA) class II to IV heart failure after worsening with treatment with an angiotensin inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist, to reduce the risks of cardiovascular mortality or heart failure hospitalisation.
For treatment of heart failure with midrange LVEF — a change in term from “mildly reduced” ejection fraction — to reduce hospitalisation and mortality risk, the guidelines suggest a number of treatments including angiotensin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and the combination agent sacubitril/valsartan but none have strong clinical trial evidence (Class IIb) .
For patients with heart failure with preserved ejection fraction, the current guidelines recommend (Class I evidence) screening for and treatment of aetiologies, as well as cardiovascular and non-cardiovascular comorbidities.
After hospitalisation for heart failure, the guidelines recommend (Class I evidence) that patients be carefully evaluated to exclude persistent signs of congestion before discharge and to optimise oral treatment, and that evidence-based oral medical treatment be administered before discharge. An early follow-up visit is recommended at 1 to 2 weeks after discharge to assess signs of congestion and drug tolerance, and to start and/or uptitrate evidence-based therapy.
The SGLT2 inhibitors canagliflozin (Invokana), dapagliflozin, empagliflozin, ertugliflozin (Steglatro), and sotagliflozin are recommended in patients with heart failure and type 2 diabetes at risk of cardiovascular events to reduce hospitalisations for heart failure, major cardiovascular events, end-stage renal dysfunction, and cardiovascular death. The SGLT2 inhibitors dapagliflozin, empagliflozin, and sotagliflozin are recommended in patients with type 2 diabetes and heart failure with reduced ejection fraction (Class I evidence). The DPP-4 inhibitor saxagliptin (Onglyza) is not recommended in patients with heart failure (Class III evidence).
Researchers have found a weakness in a key enzyme key for solid tumour cancer cells’ ability to adapt and survive when oxygen levels are low.
The findings, published in Science Advances, will help researchers develop new treatment strategies to limit the progression of solid cancer tumours, which represent the majority of tumour types that arise in the body.
As tumours advance, the blood vessels that they previously relied on become unable to provide oxygen and nutrients to all parts of the tumour, which results in areas of hypoxia. Over time, this hypoxic environment leads to a buildup of acid inside the tumour cells.
To overcome this stress, the tumour cells adapt by releasing enzymes that neutralise the acidic conditions of their environment, enabling the cells to not only survive, but develop into a more aggressive form of tumour capable of spreading to other organs. One of these enzymes is called Carbonic Anhydrase IX (CAIX).
“Cancer cells depend on the CAIX enzyme to survive, which ultimately makes it their ‘Achilles heel.’ By inhibiting its activity, we can effectively stop the cells from growing,” explained senior author Dr Shoukat Dedhar, professor in UBC faculty of medicine’s department of biochemistry and molecular biology and distinguished scientist at BC Cancer.
Previously, Dr Dedhar and colleagues had identified a unique compound, known as SLC-0111 (which is currently being evaluated in Phase 1 clinical trials) as a powerful CAIX enzyme inhibitor. Though the effectiveness of this compound in suppressing tumour growth and spread has been tested in pre-clinical models, other cellular properties diminish its effectiveness.
In this study, the researchers set out to investiagete these cellular properties and identify other weaknesses of the CAIX enzyme with the help of a powerful tool known as a genome-wide synthetic lethal screen. This tool systematically deletes one gene at a time from a cancer cell’s genome to determine if a cancer cell can be killed by eliminating the CAIX enzyme together with another specific gene.
According to Dr Dedhar, they had surprising results and point to an unexpected role of proteins and processes that control a form of cell death called ferroptosis, a form of cell death that occurs from an iron build up which weakens the tumour’s metabolism and cell membranes.
“We now know that the CAIX enzyme blocks cancer cells from dying as a result of ferroptosis,” said Dr Dedhar. “Combining inhibitors of CAIX, including SLC-0111, with compounds known to bring about ferroptosis results in catastrophic cell death and debilitates tumour growth.”
The development of drugs to induce ferroptosis is underway around the world, and this study is contributing to their work.
A commonly-used pesticide could be contributing to the global obesity epidemic, according to a new study.
Researchers discovered that chlorpyrifos slows down the burning of calories in the brown adipose tissue of mice. Reducing this burning of calories, a process known as diet-induced thermogenesis, causes the body to store these extra calories, promoting obesity. Chlorpyrifos is banned for use on foods in Canada, and also now banned in the US and, as of last year, the EU, but widely sprayed on fruits and vegetables in many other parts of the world. In South Africa it is banned for residential use but is still used in agriculture.
Scientists made the discovery after studying 34 commonly used pesticides and herbicides in brown fat cells and testing the effects of chlorpyrifos in mice fed high calorie diets. Their findings were published in Nature Communications and could have important implications for public health.
“Brown fat is the metabolic furnace in our body, burning calories, unlike normal fat that is used to store them. This generates heat and prevents calories from being deposited on our bodies as normal white fat. We know brown fat is activated during cold and when we eat,” said senior author Gregory Steinberg, professor of medicine and co-director of the Centre for Metabolism, Obesity, and Diabetes Research at McMaster.
“Lifestyle changes around diet and exercise rarely lead to sustained weight loss. We think part of the problem may be this intrinsic dialling back of the metabolic furnace by chlorpyrifos.”
Steinberg said chlorpyrifos would only need to inhibit energy use in brown fat by 40 calories every day to trigger obesity in adults, which would translate to an extra 2kg of weight gain per year.
He said that while several environmental toxins including chlorpyrifos have been associated with increasing obesity rates in both humans and animals, these studies have mostly attributed weight gain to increases in food intake and not calorie burning.
“Although the findings have yet to be confirmed in humans, an important consideration, is that whenever possible consume fruits and vegetables from local Canadian sources and if consuming imported produce, make sure it is thoroughly washed,” said Steinberg.
Screening for atrial fibrillation in 75- and 76-year-olds using thumb ECGS could reduce the risk of stroke, severe bleeding and death, according to a large-scale Swedish study.
Atrial fibrillation (AF) is associated with a five-fold increased risk of stroke, and the symptoms are often deleterious since large blood clots can form in the heart, breaking free and posing a stroke risk. Still, countries do not screen the general population for atrial fibrillation, but rather treat those patients who are discovered during routine care. This study by the Karolinska Institutet in Sweden and published in The Lancet, investigated the effectiveness of screening for AF.
“There has never really been a study that examines if it would be beneficial to screen for atrial fibrillation, which is why we wanted to investigate it,” said Emma Svennberg, cardiologist at the Karolinska University Hospital, Huddinge, and researcher at the Department of Medicine, Huddinge, Karolinska Institutet.
The study included almost 28 000 participants aged 75 or 76, randomised to be invited either to screening or to a control group, who received standard care. Of those invited to screening, more than half choose to participate. They completed a health questionnaire and performed a so-called thumb ECG (electrocardiogram), which involves placing one’s thumbs on an ECG device that measures the heart’s electrical activity.
Those without atrial fibrillation were asked to record their heart rhythm twice daily for two weeks using the ECG device which they took home. If the device registered irregular heart rhythms, the participants were referred to a cardiologist for a standardised work-up and, if there were no contra-indications, initiation of oral anticoagulant therapy.
The study’s 28 000 participants were then followed for at least five years. More detections of atrial fibrillation were recorded in the screening group, which also had a slightly lower incidence of death, stroke and severe bleeding than the control group.
“In total, 31.9 percent of those in the screening group experienced a negative event compared to 33 percent in the control group,” said Johan Engdahl, adjunct lecturer at the Department of Clinical Sciences, Danderyds Hospital, at Karolinska Institutet. “Now, that may sound like a small difference, but you must bear in mind that only about half of those invited to screening participated and it’s possible we would have seen a more pronounced difference had more people turned up for screening. Those who participated in the screening had significantly fewer negative events.”
Based on the findings, the researchers estimated that at least 2300 cases of stroke or death could be avoided per year in Sweden if a national screening of atrial fibrillation in the elderly was introduced.
In a study of more than 40 000 COVID cases, those infected with the delta variant have about twice the hospitalisation risk as those infected with the alpha variant. The findings were published in The Lancet Infectious Diseases.
The risk of hospitalisation or emergency hospital care within 14 days of infection with the delta variant was 1.45 times greater than the alpha variant. This is the first study reporting hospitalisation risk for the delta versus alpha variants based on cases confirmed by whole-genome sequencing.
Dr Gavin Dabrera, one of the study’s lead authors and a Consultant Epidemiologist at the National Infection Service, Public Health England, said: “This study confirms previous findings that people infected with Delta are significantly more likely to require hospitalisation than those with Alpha, although most cases included in the analysis were unvaccinated.”
The delta variant emerged in India in December 2020 and early studies found it to be up to 50% more transmissible than the alpha variant, which first appeared in the UK. A preliminary study from Scotland previously reported a doubling of hospitalisation risk with the delta variant over the alpha variant and it is suspected that delta is associated with more severe disease. The previous study used patients’ initial PCR test results and determined which variant they had by testing for a specific gene that is more common in the delta variant.
The researchers analysed healthcare data from 43 338 COVID-positive cases in England between 29 March and 23 May 2021. During the study period, there were 34 656 cases of the alpha variant (80%) and 8682 cases of the delta variant (20%). While the proportion of delta cases in the study period overall was 20%, it eventually encompassed two thirds of new COVID cases in the week starting 17 May 2021 (65%), effectively becoming the dominant strain in England.
Around one in 50 patients were admitted to hospital within 14 days of their first positive COVID test (2.2% alpha cases; 2.3% delta cases. After accounting for factors that are known to affect susceptibility to severe illness from COVID, including age, ethnicity, and vaccination status, the researchers found the risk of being admitted to hospital was more than doubled with the delta variant compared with the alpha variant (2.26-fold increase in risk).
It has been shown in multiple studies that full vaccination prevents both symptomatic infection and hospitalisation, for both alpha and delta variants. Indeed, in this study, only 1.8% of COVID cases (with either variant) had received both doses of the vaccine; 74% of cases were unvaccinated, and 24% were partially vaccinated. With the small number of vaccinated people being hospitalised, it is not possible to statistically compare hospitalisation risk between alpha and delta in such cases, so the results of the study apply to unvaccinated or partially vaccinated cases.
One of the study’s lead authors, Dr Anne Presanis, Senior Statistician at the MRC Biostatistics Unit, University of Cambridge, said: “Our analysis highlights that in the absence of vaccination, any Delta outbreaks will impose a greater burden on healthcare than an Alpha epidemic. Getting fully vaccinated is crucial for reducing an individual’s risk of symptomatic infection with Delta in the first place, and, importantly, of reducing a Delta patient’s risk of severe illness and hospital admission.”
Limitations to the study included some demographic groups possibly being more likely to seek hospital care, which could have biased the results, and there may have been changes in hospital admission policy during the period of the study, although adjustment for demographics and calendar time should have minimised such bias. The authors also did not have access to information about patients’ pre-existing health conditions, which are known to affect the risk of severe illness from COVID. By using age, gender, ethnicity, and estimated level of socioeconomic deprivation, they were able to account for this.
SARS-CoV-2 viruses (yellow) infecting a human cell. Credit: NIH
Dr Shankara Chetty, a general practitioner with a natural science background in genetics, advanced biology, microbiology and biochemistry, has been critically reviewing information that has arisen from observations of the COVID pandemic from around the world. Knowledge gained from a broad natural science background convinced him that there was a missing element in these reports. This is a summary of an article published in Issue 5 of Modern Medicine in 2020.
“A wealth of knowledge of hospital presentations, pathology and investigations has been generated, but there has been a distinct lack of information regarding initial presentation, progression and pathogenesis,” said Dr Chetty. Type 1 hypersensitivity reaction When COVID arrived in South Africa, Dr Chetty isolated himself so as to limit interactions with family and the public and erected a tented field clinic in his practice parking so as to be able to examine and follow up on every COVID patient without risk to his other patients. According to him he had a theoretical understanding of the possible pathogenesis but needed to verify his suspicions.
“From the examination, treatment and follow up of over 200 symptomatic COVID patients, it is my opinion that COVID illness has two aetiologies. It is initially a respiratory viral infection with typical symptoms, progression and outcomes over the initial 7 days. On around day 7, a Type 1 hypersensitivity reaction is triggered in those that are sensitive, leading to the sequelae typically seen on admission.
“This reaction causes the release of chemical mediators in the ling, resulting in inflammation, oedema, and in time, massive cell damage. The resultant cellular disruption is what triggers the ‘cytokine storm’ in an attempt to repair damaged cells and remove debris. This release of cytokine produces the variety of pathologies that are seen,” said Dr Chetty.
Rapid response to treatment His treatment protocol included the use of hydrochloroquine, azithromycin and doxyclcline to combat the viral component and antihistamines, leukotriene receptor antagonists and steroids, amongst others, for the Type 1 hypersensitivity reaction. This protocol produced consistent outcomes, no sequelae, and rapid recovery of all patients. In all, they had no deaths, no hospitalisations and recover of all patients, regardless of age, within 14 days.
“Outcomes of identifying and treating a Type 1 hypersensitivity reaction were most telling in the more severe dyspnoiec patients, with saturations below 85% on presentation that had improvement to over 95% in 24 hours, with outpatient management on room air, negating the need for oxygen or hospitalisation,” said Dr Chetty.
According to Dr Chetty, the rapid response to these medications used to treat Type 1 hypersensitivity reactions confirmed its existence. This could have some serious implications for the future management of the COVID pandemic. Monitoring for a hypersensitivity reaction and prompt treatment would decrease morbidity and mortality significantly.
SARS-CoV-2 viruses (yellow) infecting a human cell. Credit: NIH
Viral load as determined by cycle threshold (Ct) has limited utility in guiding decisions regarding isolation and quarantine of COVID patients, according to a study of COVID cases in university students.
Though some in vitro studies indicate that virus load levels in infected individuals affects the successful rate of virus transmission, whether the viral load carried at the individual level can determine transmissibility was unknown. In this study published in The Journal of Molecular Diagnostics, university students underwent regular testing and contact tracing after positive tests, and significant overlap in cycle thresholds (Ct) was found between spreaders and nonspreaders. This brings into question using Ct values to determine transmission rates, with even those with low viral loads able to transmit the virus. Real-time RT-PCR Ct values represent the number of amplification cycles required for the target gene to exceed a threshold level. Ct values are therefore inversely related to viral load and can provide an indirect method of quantifying the copy number of viral RNA in the sample; however, the use of Ct values as a proxy of viral load is influenced by the assay itself (correlation would stand in the linear dynamic range of the specific RT-PCR assay used) and factors within the sample matrix that can affect amplification efficiency
“We wanted to find whether there was a scientifically sound way to quickly triage students with potential high-risk exposure to COVID positive students for quarantine,” explained co-lead authors Patrice Delafontaine, MD, Department of Medicine, and Xiao-Ming Yin, MD, PhD, Departments of Pathology and Laboratory Medicine, Tulane University School of Medicine. “Some studies have found that the Ct value of the RT-PCR assay is a surrogate for infectivity, and cutoff Ct values have been proposed as a way to guide isolation practices. Through testing and contact tracing, we found that Ct value could not predict transmissibility. We should not overlook positive patients with low viral load, and all positive patients should be quarantined.”
A high-throughput SARS-CoV-2 surveillance testing program was established at Tulane University to support isolation and contact tracing efforts at the campus. Students were tested twice weekly and asked about symptoms they may be experiencing. Contact tracers spoke to all positive case subjects to identify close contacts. The study looked at 7440 patients who were screened between September 1, 2020 and October 31, 2020, among whom 602 positive cases were identified. From this group, 195 index cases were identified with one or more reported close contacts, who were then tested during their mandated 14-day quarantine period for evidence of transmission from the associated index cases. Of these index cases, 48.2% had at least one contact who became COVID positive, whereas 51.8% of the index cases were nonspreaders with no contacts who subsequently tested positive. Mean Ct values of the spreaders and the nonspreaders were nearly identical.
The researchers then reversed approach, where index cases were traced for 481 students undergoing quarantine due to known exposure to the disease. Eighteen percent of the students became positive during their quarantine. Index cases for the 481 quarantined students were considered spreaders if they were linked to one or more quarantine students with a positive test result, or nonspreaders if they were associated only with students with negative test results. Mean Ct values of the spreader and the nonspreader groups were similar.
The researchers next identified and evaluated 375 positive cases to assess the relationship between symptom presentation and Ct values. Reported symptoms included lethargy, fever, headache, cough, runny nose and gastrointestinal symptoms. Mean and median Ct values were lower in symptomatic cases than in asymptomatic cases, indicating a higher viral load, This suggests that infections with a higher viral load could more often lead to symptom development, or that symptomatic individuals tend to have higher viral loads or maintain their viral loads for a longer period of time. Ct levels may be useful at a population level, in association with symptomatic presentation, to indicate the likelihood of transmission. These values may thus have epidemiologic or surveillance importance.
“Taken together, these index cases suggest that Ct values alone do not predict transmission risk and reporting of Ct values at the individual level, such as by setting a cutoff value of 32, would provide little diagnostic value for case management,” note Dr. Delafontaine and Dr. Yin. “A sensitive and robust SARS-CoV-2 diagnostic testing method is needed to effectively control viral transmission by maximizing the ability to identify and quarantine even those with a low level of virus.”
HIV infecting a human cell. Credit: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases/NIH
A large, in-depth look at US patients taking HIV-prevention drug therapy found strong adherence soon after patients get the prescription, but less consistent use thereafter, particularly among groups considered to be high-priority.
The study, published in JAMA Network Open, examined data from 13 906 members of Kaiser Permanente referred for pre-exposure prophylaxis, or PrEP, therapy between 2012 and 2019. The study found certain groups were more likely to stop taking PrEP: young people, Black and Latino individuals, women, and people with substance use disorders.
The findings suggest targeted strategies are needed to support use of this effective prevention in high-risk groups, said lead author Carlo Hojilla, RN, PhD, a research fellow with the Kaiser Permanente Northern California Division of Research.
“The findings have important implications that suggest access to health care is a great way to get people in the door, but we need more effective strategies for making sure people who have an ongoing need for PrEP stay on the medication,” said Dr Hojilla. “These are groups we want to reach, and we need innovative approaches to keep them engaged in PrEP care.”
Some 88% of patients referred for HIV prevention care received a PrEP prescription, and most (98%) of them filled their initial prescriptions. “These findings were encouraging,” Dr Hojilla said. “Kaiser Permanente has managed to do really well increasing uptake of PrEP therapy.” However, significant inconsistency in use was seen with about half of users discontinuing PrEP at least once; 60% of those filled a prescription again though the study did not explore the reasons for this. Some users may have discontinued PrEP because of a decrease in risk for HIV acquisition, the authors speculated. Medical mistrust, stigma, homophobia, and transphobia as barriers to PrEP uptake and persistence in some communities have been documented in prior studies. Cost was known to be a concern for some, and the study was done before PrEP was provided at no cost, Dr Hojilla said.
The study was also done before the introduction of a new dosing scheme known as 2-1-1, or on-demand, which allows the user to take PrEP only around the time of a potential exposure to HIV, with a similar level of effectiveness as daily dosing. It’s possible that some of the discontinuation reflected in the study was from patients who opted to not take the drug daily because they had only occasional risk exposure, even prior to 2-1-1 dosing being formally recommended, said senior author Jonathan Volk, MD, an infectious disease specialist with The Permanente Medical Group.
No new HIV infections were seen in those remaining on PrEP, the study found. “This shows how incredibly well PrEP works when taken,” Dr Volk said. “But there are important opportunities for us to maximise the population level impact of this vital therapy. To do this, we need to avoid attrition along the care continuum, especially by assisting patients to stay on PrEP throughout periods of risk for HIV acquisition.”
