Researchers found that small declines in blood lead levels were associated with long-term cardiovascular health improvements in American Indian adults. Participants who had the greatest reductions in blood lead levels saw their systolic blood pressure fall by about 7mmHg, comparable to the effects of antihypertensives.
The findings as reported from researchers at Columbia University Mailman School of Public Health and NIEHS and NHLBI are published in the Journal of the American Heart Association.
“This is a huge win for public health,” said senior author Anne E. Nigra, PhD, assistant professor of environmental health sciences at Columbia Mailman School of Public Health.
“We saw that even small decreases in a person’s blood lead levels can have meaningful health outcomes.”
Nigra and her co- authors, including Wil Lieberman-Cribbin, MPH, also at Columbia Mailman School, credit these improvements in large part to public health and policy changes that have occurred over the last few decades.
In addition to seeing improvements in systolic blood pressure, the investigators found that reductions in blood lead levels were associated with reductions in a marker associated with hypertrophic cardiomyopathy and heart failure.
To conduct this research, investigators partnered with 285 American Indian adults through an extension of the Strong Heart Study, the largest study following cardiovascular health outcomes and risk factors among American Indian adults.
The researchers looked at blood lead levels and blood pressure readings over time in participants living in one of four tribal communities. Lead was first measured in blood collected during the 1997–1999 study visit and again in blood collected during a follow-up visit between 2006–2009.
During this time, participants’ blood pressure was taken and they participated in medical exams, including echocardiographs to assess their heart’s structure and function. Multiple factors were controlled for, including social variables, cardiovascular disease risks, and medical history.
At the start of the study, the average blood lead level was 2.04µg/dL. Throughout the study, the average blood lead level fell by 0.67µg/dL, or 33%.
The most significant changes, categorized by participants with average starting blood lead levels of 3.21 µg/dL and who experienced reductions of about 1.78 µg/dL, or 55%, were linked to a 7mmHg reduction in systolic blood pressure.
“This is a sign that whatever is happening in these communities to reduce blood lead levels is working,” said Mona Puggal, MPH, an epidemiologist in the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI). “The reductions in blood pressure are also comparable to improvements you would see with lifestyle changes, such as getting 30 minutes of daily exercise, reducing salt intake, or losing weight.”
The reductions in blood lead levels observed in the study are similar to those seen in the general US population following policies and efforts implemented within the past 50 years to reduce lead exposure through paint, gasoline, water, plumbing, and canned items.
A mouse-based study to investigate memory loss in people who experience repeated head impacts, such as athletes, suggests the condition could potentially be reversed. The research in mice finds that amnesia and poor memory following head injury is due to inadequate reactivation of neurons involved in forming memories.
The study, conducted by researchers at Georgetown University Medical Center in collaboration with Trinity College Dublin, Ireland, is reported in the Journal of Neuroscience.
Importantly for diagnostic and treatment purposes, the researchers found that the memory loss attributed to head injury was not a permanent pathological event driven by a neurodegenerative disease.
Indeed, the researchers could reverse the amnesia to allow the mice to recall the lost memory, potentially allowing cognitive impairment caused by head impact to be clinically reversed.
The Georgetown investigators had previously found that the brain adapts to repeated head impacts by changing the way the synapses in the brain operate, which can cause trouble in memory storage and retrieval.
In their new study, investigators were able to trigger mice to remember memories that had been forgotten due to head impacts.
“Our research gives us hope that we can design treatments to return the head-impact brain to its normal condition and recover cognitive function in humans that have poor memory caused by repeated head impacts,” says the study’s senior investigator, Mark Burns, PhD, a professor and Vice-Chair in Georgetown’s Department of Neuroscience and director of the Laboratory for Brain Injury and Dementia.
In the new study, the scientists gave two groups of mice a new memory by training them in a test they had never seen before. One group was exposed to a high frequency of mild head impacts for one week (similar to contact sport exposure in people) and one group were controls that didn’t receive the impacts. The impacted mice were unable to recall the new memory a week later.
“Most research in this area has been in human brains with chronic traumatic encephalopathy (CTE), which is a degenerative brain disease found in people with a history of repetitive head impact,” said Burns.
“By contrast, our goal was to understand how the brain changes in response to the low-level head impacts that many young football players regularly experience.”
Researchers have found that, on average, college football players receive 21 head impacts per week with defensive ends receiving 41 head impacts per week.
The number of head impacts to mice in this study were designed to mimic a week of exposure for a college football player, and each single head impact by itself was extraordinarily mild.
Using genetically modified mice allowed the researchers to see the neurons involved in learning new memories, and they found that these memory neurons (the “memory engram”) were equally present in both the control mice and the experimental mice.
To understand the physiology underlying these memory changes, study first author Daniel P. Chapman, PhD, said, “We are good at associating memories with places, and that’s because being in a place, or seeing a photo of a place, causes a reactivation of our memory engrams. This is why we examined the engram neurons to look for the specific signature of an activated neuron. When the mice see the room where they first learned the memory, the control mice are able to activate their memory engram, but the head impact mice were not. This is what was causing the amnesia.”
The researchers were able to reverse the amnesia to allow the mice to remember the lost memory using lasers to activate the engram cells.
“We used an invasive technique to reverse memory loss in our mice, and unfortunately this is not translatable to humans,” Burns adds.
“We are currently studying a number of non-invasive techniques to try to communicate to the brain that it is no longer in danger, and to open a window of plasticity that can reset the brain to its former state.”
Daniel P. Chapman, Sarah D. Power, Stefano Vicini, Tomás J. Ryan, Mark P. Burns. Amnesia after repeated head impact is caused by impaired synaptic plasticity in the memory engram. The Journal of Neuroscience, 2024; e1560232024 DOI: 10.1523/JNEUROSCI.1560-23.2024
Rapid-acting antidepressants, including ketamine, scopolamine and psilocybin, have been found to have immediate and lasting positive effects on mood in patients with major depressive disorder but how these effects arise is unknown. New research led by the University of Bristol and published in Science Translational Medicine explored their neuropsychological effects and found that all three of these drugs can modulate affective biases associated with learning and memory.
Negative affective biases are a core feature of major depressive disorder. Affective biases occur when emotions alter how the brain processes information and negative affective biases are thought to contribute to the development and continuation of depressed mood.
The research team used an affective bias test, based on an associative learning task, to investigate the effects of rapid-acting antidepressants (RAADs) in rats.
They found that all the treatments were able to reduce negative affective biases associated with past experiences but there were additional characteristics of the dissociative anaesthetic, ketamine, and the serotonergic psychedelic, investigational COMP360 psilocybin (Compass Pathways’ proprietary formulation of synthetic psilocybin), which could explain why the effects of a single treatment can be long-lasting.
The findings suggest that these sustained effects are due to adaptive changes in the brain circuits which control affective biases, and these can influence how past experiences are remembered.
The effects at low doses were very specific to affective bias modulation and were localised to the prefrontal cortex of the brain, a region known to play an important role in mood.
Emma Robinson, Professor of Psychopharmacology in the School of Physiology, Pharmacology & Neuroscience at Bristol, and lead author, said: “Using a behavioural task we showed that drugs that are believed to have rapid and sustained benefits in depressed patients, specifically modulate affective biases associated with past experiences, something which we think is really important for understanding why they can improve a patient’s mood so quickly.
“We also found differences in how ketamine, scopolamine and COMP360 psilocybin interact with these neuropsychological mechanisms which may explain why the effects of a single treatment in human patients can be long-lasting, days (ketamine) to months (psilocybin).
“By using an animal model, we have been able to investigate these important interactions with learning and memory processes and neural plasticity and propose a two-stage model that may explain the effects we observe.”
In the task, each animal learnt to associate a specific digging material with a food reward under either treatment or control conditions.
The treatment condition is designed to generate a change in the animal’s affective state and a choice test is used to quantify the affective bias this generates.
Acute treatment with the RAADs ketamine, scopolamine, or psilocybin prevented the retrieval of the negative affective bias induced in this model.
However, the most exciting finding was at 24 hours after treatment when low, but not high, doses of ketamine and psilocybin led to a re-learning effect where the negatively biased memory was retrieved with a more positive affective valence.
Only psilocybin, but not ketamine or scopolamine treatment also positively biased new experiences.
Exploring in more detail the re-learning effects of ketamine in the studies, the researchers found they were protein synthesis-dependent, localised to the medial prefrontal cortex and could be modulated by cue-reactivation, consistent with their predictions of experience-dependent neural plasticity.
The study’s findings propose a neuropsychological mechanism that may explain both the immediate and sustained effects of RAADs, potentially linking their effects on neural plasticity with mood.
Restricting calories is known to improve health and increase lifespan, but much of how it does so remains a mystery, especially in regard to how it protects the brain. Now, scientists from the Buck Institute for Research on Aging have uncovered a role for a gene called OXR1 that is necessary for the lifespan extension seen with dietary restriction and is essential for healthy brain aging.
“When people restrict the amount of food that they eat, they typically think it might affect their digestive tract or fat buildup, but not necessarily about how it affects the brain,” said Kenneth Wilson, PhD, Buck postdoc and first author of the study, published in Nature Communications. “As it turns out, this is a gene that is important in the brain.”
The team additionally demonstrated a detailed cellular mechanism of how dietary restriction can delay aging and slow the progression of neurodegenerative diseases. The work, done in fruit flies and human cells, also identifies potential therapeutic targets to slow aging and age-related neurodegenerative diseases.
“We found a neuron-specific response that mediates the neuroprotection of dietary restriction,” said Buck Professor Pankaj Kapahi , PhD, co-senior author of the study. “Strategies such as intermittent fasting or caloric restriction, which limit nutrients, may enhance levels of this gene to mediate its protective effects.”
“The gene is an important brain resilience factor protecting against aging and neurological diseases,” said Buck Professor Lisa Ellerby, PhD, co-senior author of the study.
Understanding variability in response to dietary restriction
Members of the team have previously shown mechanisms that improve lifespan and healthspan with dietary restriction, but it was not clear why there is so much variability in response to reduced calories across individuals and different tissues. This project was started to understand why different people respond to diets in different ways.
The team began by scanning about 200 strains of flies with different genetic backgrounds. The flies were raised with two different diets, either with a normal diet or with dietary restriction, which was only 10% of normal nutrition. Researchers identified five genes which had specific variants that significantly affected longevity under dietary restriction. Of those, two had counterparts in human genetics.
The team chose one gene to explore thoroughly, called “mustard” (mtd) in fruit flies and “Oxidation Resistance 1” (OXR1) in humans and mice. The gene protects cells from oxidative damage, but the mechanism for how this gene functions was unclear. The loss of OXR1 in humans results in severe neurological defects and premature death. In mice, extra OXR1 improves survival in a model of amyotrophic lateral sclerosis (ALS).
The link between brain aging, neurodegeneration and lifespan
To figure out how a gene that is active in neurons affects overall lifespan, the team did a series of in-depth tests. They found that OXR1 affects a complex called the retromer, which is a set of proteins necessary for recycling cellular proteins and lipids. “The retromer is an important mechanism in neurons because it determines the fate of all proteins that are brought into the cell,” said Wilson. Retromer dysfunction has been associated with age-related neurodegenerative diseases that are protected by dietary restriction, specifically Alzheimer’s and Parkinson’s diseases.
Overall, their results told the story of how dietary restriction slows brain aging by the action of mtd/OXR1 in maintaining the retromer. “This work shows that the retromer pathway, which is involved in reusing cellular proteins, has a key role in protecting neurons when nutrients are limited,” said Kapahi. The team found that mtd/OXR1 preserves retromer function and is necessary for neuronal function, healthy brain aging, and lifespan extension seen with dietary restriction.
“Diet is influencing this gene. By eating less, you are actually enhancing this mechanism of proteins being sorted properly in your cells, because your cells are enhancing the expression of OXR1,” said Wilson.
The team also found that boosting mtd in flies caused them to live longer, leading researchers to speculate that in humans excess expression of OXR1 might help extend lifespan. “Our next step is to identify specific compounds that increase the levels of OXR1 during aging to delay brain aging,” said Ellerby.
“Hopefully from this we can get more of an idea of why our brains degenerate in the first place,” said Wilson.
“Diet impacts all the processes in your body,” he said. “I think this work supports efforts to follow a healthy diet, because what you eat is going to affect more than you know.”
Co-prescribing potency drugs such as Viagra and organic nitrates for angina is associated with a 35–40% increased mortality risk and about 70% higher risk of heart attack and heart failure. This is according to a Swedish registry study published in the Journal of the American College of Cardiology. The Swedish researchers are now urging caution.
Drugs for erectile dysfunction or impotence containing phosphodiesterase inhibitors type 5 are contraindicated in the treatment of angina with organic nitrates. Because the two types of drugs enhance each other’s antihypertensive effect, they can cause serious side effects, including death, if taken together.
But many people who treat angina with organic nitrates use the medication as emergency relief for a sudden onset of angina. The medication is quickly absorbed by the body, exerts its effect, and then breaks down quickly again. It is not usually a permanent treatment, although maintenance treatment is possible.
Does not necessarily indicate an increased risk
Potency drugs are also taken as needed, which theoretically makes it possible to separate the two treatments in time to avoid side effects. If patients are aware of these factors, co-prescribing does not necessarily mean an increased risk.
Previous studies have shown that an increasing number of men who treat their angina with organic nitrates are also prescribed potency drugs. However, there is no evidence that side effects have increased.
The picture is not entirely clear, as it has also been shown that type 5 phosphodiesterase inhibitors for men with cardiovascular disease without angina reduce the risk of death and heart failure.
“There is an increasing demand for medication for erectile dysfunction from men with cardiovascular disease. And even if these drugs are beneficial for most men with cardiovascular disease, those who are also treated with nitrates need to consider the benefits of the drug against the cardiovascular risks,” says first author Ylva Trolle Lagerros, Associate Professor at the Department of Medicine at Karolinska Institutet.
To find out what the actual risk of concurrent prescribing is, the researchers used Swedish health registers between 2005 and 2013. They found nearly 61 500 men who had been prescribed organic nitrates, of which just over 5700 had also been prescribed one of the potency drugs in question. A clear majority of those who had a prescription for both medications used nitrates as an emergency treatment only.
Adjusted for differences
The men who received the drugs were on average nine years younger and significantly healthier than those who did not receive them. The researchers therefore had to adjust for these and other differences.
The adjusted results show that co-prescribing potency drugs with type 5 phosphodiesterase inhibitors and organic nitrates is associated with a 35–40% increased risk of death. In addition, the researchers show an approximately 70% increased risk of heart attack and heart failure. This suggests that the theoretical separation in time of the treatments does not seem to work fully.
“We want to point out the importance of careful and patient-centered consideration before prescribing this type of potency medication to men treated with nitrates,” says Ylva Trolle Lagerros.
Babies and toddlers exposed to television or video viewing may be more likely to exhibit atypical sensory behaviours, such as being disengaged and disinterested in activities, seeking more intense stimulation in an environment, or being overwhelmed by sensations like loud sounds or bright lights, according to data from researchers at Drexel’s College of Medicine published in the journal JAMA Pediatrics.
According to the researchers, children exposed to greater TV viewing by their second birthday were more likely to develop atypical sensory processing behaviours, such as “sensation seeking” and “sensation avoiding,” as well as “low registration” – being less sensitive or slower to respond to stimuli, such as their name being called, by 33 months old.
Sensory processing skills reflect the body’s ability to respond efficiently and appropriately to information and stimuli received by its sensory systems, such as what the toddler hears, sees, touches, and tastes.
The team pulled 2011-2014 data on television or DVD-watching by babies and toddlers at 12- 18- and 24-months from the National Children’s Study of 1471 children (50% male) nationwide.
Sensory processing outcomes were assessed at 33 months using the Infant/Toddler Sensory Profile (ITSP), a questionnaire completed by parents/caregivers, designed to give insights on how children process what they see, hear and smell, etc.
ITSP subscales examine children’s patterns of low registration, sensation seeking, such as excessively touching or smelling objects; sensory sensitivity, such as being overly upset or irritated by lights and noise; and sensation avoiding – actively trying to control their environment to avoid things like having their teeth brushed. Children score in “typical,” “high” or “low” groups based on how often they display various sensory-related behaviours. Scores were considered “typical” if they were within one standard deviation from the average of the ITSP norm.
Measurements of screen exposure at 12-months were based on caregiver responses to the question: “Does your child watch TV and/or DVDs? (yes/no),” and at 18- and 24- months based on the question: “Over the past 30 days, on average, how many hours per day did your child watch TV and/or DVDs?”
The findings suggest:
At 12 months, any screen exposure compared to no screen viewing was associated with a 105% greater likelihood of exhibiting “high” sensory behaviours instead of “typical” sensory behaviours related to low registration at 33 months
At 18 months, each additional hour of daily screen time was associated with 23% increased odds of exhibiting “high” sensory behaviours related to later sensation avoiding and low registration.
At 24 months, each additional hour of daily screen time was associated with a 20% increased odds of “high” sensation seeking, sensory sensitivity, and sensation avoiding at 33 months.
The researchers adjusted for age, whether the child was born prematurely, caregiver education, race/ethnicity and other factors, such as how often the child engages in play or walks with the caregiver.
The findings add to a growing list of concerning health and developmental outcomes linked to screen time in infants and toddlers, including language delay, autism spectrum disorder, behavioural issues, sleep struggles, attention problems and problem-solving delays.
“This association could have important implications for attention deficit hyperactivity disorder and autism, as atypical sensory processing is much more prevalent in these populations,” said lead author Karen Heffler, MD, an associate professor of Psychiatry in Drexel’s College of Medicine. “Repetitive behaviour, such as that seen in autism spectrum disorder, is highly correlated with atypical sensory processing. Future work may determine whether early life screen time could fuel the sensory brain hyperconnectivity seen in autism spectrum disorders, such as heightened brain responses to sensory stimulation.”
Atypical sensory processing in kids with autism spectrum disorder (ASD) and ADHD manifests in a range of detrimental behaviours. In children with ASD, greater sensation seeking or sensation avoiding, heightened sensory sensitivity and low registration have been associated with irritability, hyperactivity, eating and sleeping struggles, as well as social problems. In kids with ADHD, atypical sensory processing is linked to trouble with executive function, anxiety and lower quality of life.
“Considering this link between high screen time and a growing list of developmental and behavioural problems, it may be beneficial for toddlers exhibiting these symptoms to undergo a period of screen time reduction, along with sensory processing practices delivered by occupational therapists,” said Heffler.
The American Academy of Pediatrics (AAP) discourages screen time for babies under 18–24 months. Live video chat is considered by the AAP to be okay, as there may be benefit from the interaction that takes place. AAP recommends time limitations on digital media use for children ages two to five years to typically no more than one hour per day.
“Parent training and education are key to minimising, or hopefully even avoiding, screen time in children younger than two years,” said senior author David Bennett, PhD, a professor of Psychiatry in Drexel’s College of Medicine.
New research shows grass allergen levels are more consistently associated with hay fever symptoms than grass pollen counts.
The research, published in The Journal of Allergy and Clinical Immunology and led by King’s College London and Imperial College London, shows for the first time that measuring airborne allergen levels will help people with hay fever better control their symptoms.
In the UK, 1 in 4 adults suffer from hay fever from late-March to September. Symptoms include a runny or blocked nose, sneezing and coughing and itchy, red or watery eyes.
Hay fever can make lung conditions such as asthma worse, causing wheezing and breathing difficulties which can lead to hospitalisation.
Many people with hay fever monitor peak pollen times to manage their symptoms. In the UK (as well as South Africa), pollen grains are manually measured to find the daily pollen count.
But the study authors say measuring allergen levels instead will be more accurate as each pollen grain can release a different amount of allergen each day, and it is the allergens in the air that are primarily responsible for causing hay fever symptoms.
Currently, there is no regular monitoring of allergen levels in the UK or elsewhere.
Authors collected daily symptom and medication scores from adult participants in an allergy clinical trial as well as daily counts of asthma hospital admissions in London.
They measured grass pollen counts and but also sampled air for the grass pollen Phl p 5 grass allergen protein in the same location at King’s College London over the same time period.
First author Dr. Elaine Fuertes, from Imperial College London, said: “Grass pollen is the most common hay fever trigger. In this study, we measured grass allergen (Phl p 5) levels and found this was more consistently associated with allergic respiratory symptoms than grass pollen counts.”
Senior author Professor Stephen Till, from King’s College London, said: “High pollen season can be serious for people who suffer with hay fever, and can trigger severe asthma attacks in those who are allergic to grass pollen. This study shows there is a superior way of measuring pollen allergens in the air than the traditional pollen count. Monitoring grass allergen instead of grass pollen counts gives results that are more consistently linked to patients’ symptoms and could allow people with serious allergies to be better prepared during the pollen season.”
Research is ongoing to see whether regular measurement of allergen levels can become the standard in the UK, and whether there are other environmental factors, such as meteorological factors including temperature, wind, humidity, and air pollutants, that influence how much allergen each pollen grain releases.
“The path to ending AIDS is clear,” states a recent UNAIDS report. “HIV responses succeed when they are anchored in strong political leadership, have adequate resources, follow the evidence, use inclusive and rights-based approaches, and pursue equity. Countries that are putting people first in their policies and programmes are already leading the world on the journey to ending AIDS by 2030,” it reads.
Ending AIDS and the HIV epidemic mean different things to different people.
This very ambitious language is found in Sustainable Development Goal 3.3: “By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases”. The global target is to reduce the newly HIV infected population (per 1 000 uninfected population) to 0.05 by 2025 and to 0.025 by 2030.
Another version is “ending AIDS as a public health threat by 2030” which has been characterised as being “consistent with the three zeros vision: zero deaths, zero new infections and zero discrimination, operationalized as a 90% reduction of annual new HIV infections and AIDS-related deaths in 2030 compared to 2010”.
A third approach calls for countries to reach the 95-95-95 targets – 95% of people living with HIV are diagnosed, 95% of those that have been diagnosed are on antiretroviral treatment and 95% of those on treatment are virally suppressed – by 2025.
A fourth, more realistic approach, is to reduce the number of new HIV infections below the number of deaths from HIV – labelled ‘epidemic control’ – to an endemic status beyond 2030.
Regardless of the definition of ‘ending AIDS’, what should South Africa do in determining its path towards reducing the burden of HIV?
First, let’s start with what we think the HIV epidemic will look like in 2030. Whilst we do not have a crystal ball, we do have a well-recognised mathematical model – the Thembisa model, which is also used as the basis for UNAIDS’s HIV estimates for South Africa. The latest Thembisa model outputs, published last year, include projections up to 2030.
The model projects that in 2030 there will be around 128 535 new HIV infections with the bulk of these, over 54% (70 412) being young women between the ages of 15 and 24 years. Using the definition of a 90% decrease in new infections between 2010 and 2030, South Africa is projected to reach 65.7%.
The model projects that in 2030 around 8.1 million people will be living with HIV with 6.4 million being on antiretroviral treatment. The total number of AIDS deaths projected by the model in 2030 is 40 486 compared to 149 257 deaths in 2010. (This is a 72.9% reduction – not quite the 90% expected by one of the definitions noted above).
How well is the country doing in reaching the 95-95-95 targets?
According to the Thembisa model, the percentage of people ever tested for HIV stood at 83.7% in 2022 (projected to reach 86.1% in 2030). The percentage of people living with HIV who had been diagnosed was at 94.5% in 2022 and projected to reach 96.4% in 2030. The percentage of diagnosed people on treatment in 2022 stood at 77.4% and is projected to reach 81.1% in 2030.
The percentage of all people living with HIV who were virally suppressed was at 65.4% in 2022 and projected to reach 71.3% in 2030. (These percentages are slightly higher if a viral load cut-off of 1000 copies/mL rather than 400 is used). This means only one of the 95s (percent diagnosed) is expected to be reached. (If the third 95 is defined as percentage of people on HIV treatment who are virally suppressed, rather than percentage of all people living with HIV who are virally suppressed, it will also be met.)
A more optimistic picture has been reported by the Human Sciences Research Council (HSRC) through their recently completed national survey. This survey found that 90% of 15-year-olds and older living with HIV knew their status (this included self-reported status), with 91% of them on treatment, and 94% of those on treatment being virally suppressed (at the 1000 copies/mL threshold).
Based on the Thembisa projections, South Africa is not expected to reach epidemic control by 2030. So, what needs to be done to achieve significantly fewer new infections and deaths?
What to do
In his address to the 2023 South African AIDS conference, the Minister of Health outlined what the Department of Health considered as necessary. He noted that the country has achieved 94:77:92 against the UNAIDS targets – far lower than the HSRC survey found. This means that, according to the Department’s data, there are over two million people who are living with HIV but not on treatment and a further 1.6 million people who are on treatment but are not virally suppressed. This is far higher than the 1.9 million that the HSRC survey suggests are not on treatment and not virally suppressed.
Regardless of which data is correct, it is urgent that these patients are found, initiated on treatment and supported to reach viral suppression.
While the Minister did not quantify the number of people living with HIV who are not being reached, he did outline the following interventions that he proposed should be prioritised:
Immediate implementation of the revised and consolidated ART Clinical Guidelines, which includes an integrated approach on prevention of vertical transmission, a focus on TB/HIV given high levels of coinfection, and differentiated service delivery.
A focus on the 100 identified health facilities which are lagging in reaching the 2nd and 3rd 95s (treatment coverage and viral suppression).
The need to close the testing and treatment gaps for men and children through HIV self-testing and index testing (an approach whereby the exposed contacts of an HIV-positive person are notified and offered an HIV test).
A focus on re-engaging those who have stopped taking treatment and scaling up of community treatment, 3-month dispensing of treatment medication as well as the use of community health workers in tracking and tracing people living with HIV.
A greater effort on combination prevention, using all currently available prevention methods as well as Cab-LA, which is an antiretroviral HIV prevention injection that provides two months of protection per shot.
These are well known interventions and if health workers and communities are committed to their urgent and full implementation, it is possible to achieve further reductions in new HIV infections, as well as further reductions in death. However, as most deaths in people living with HIV are due to TB, a greater focus should be placed on testing people living with HIV for TB – given the estimated 59% co-infection rates; and ensuring that they are successfully treated and initiating those that test negative for TB, on TB preventive therapy.
How do the Minister’s prescriptions align with the recently completed HIV investment case?
As recently reported in Spotlight, the only HIV intervention found to be cost saving for the health system in South Africa was condoms. However, the recent HSRC survey found that reported condom use at last sexual encounter declined in all age categories. The 2017 survey found that 68% of males aged 15-24 years reported condom use, compared to 50.6% in the latest report. Similarly, 53.4% of males aged 25-49 years reported condom use in 2017 compared to 44% in 2023.
Whilst the Minister noted in his speech at the South African AIDS conference the availability of Cab-LA for HIV prevention, the investment case found that at the current price, this was not a good investment and unaffordable! The investment case outputs suggest that it was most cost effective to increase HIV self-testing, focusing on improving linkage to treatment, as well as increasing the rate of testing infants for HIV at 10 weeks after birth. It is therefore important to prioritise HIV interventions, as noted in the investment case, given that the National Treasury has reduced the HIV conditional grant by R1 billion and that the National Strategic Plan for 2023-2028 is not fully funded!
In UNAIDS’s path to ending AIDS, the organisation suggests what countries can do to intervene. These include: political commitment to ending AIDS, respecting human rights, engaging affected communities, removing criminalising policies and laws, addressing gender inequities, stigma and discrimination, as well as a focused approach to prevention. Some of the barriers to ending AIDS are listed as: inadequate prevention programmes, large treatment gaps, and lack of sufficient funding.
In summary, to respond to the call to end AIDS by 2030:
Firstly, it is critical to agree on its definition.
Secondly, it is important to have accurate data, including at sub-national level given that national averages hide variability by province and district. District level data by sex, age and by key populations will allow a more targeted approach to reaching those that the health system typically does not reach.
While South Africa largely funds much of its HIV response – despite the reduction noted above, the possibility of reduced external funding – through PEPFAR (a US government’s effort to address HIV globally) and The Global Fund (an international financing and partnership organisation to fight AIDS, TB and Malaria) in the future, requires the country to move to a more efficient HIV response, with more precise targeting and with greater levels of accountability. For this more granular and real time data will be required.
*Dr Pillay is extraordinary professor at the Department of Global Health, Stellenbosch University and director for HIV and TB delivery at the Bill and Melinda Gates Foundation.
Note: Spotlight receives funding from the Gates Foundation, but is editorially independent and a member of the South African Press Council. The views expressed in this opinion piece are not necessarily shared by Spotlight.
In social media posts on the community network Reddit, users reported reduced cravings for alcohol when taking drugs intended to treat Type 2 diabetes and obesity. Across a number of threads – with titles such as “Did scientists accidentally invent an anti-addiction drug?” and “I don’t know if this is a side effect but … Mounjaro makes me drink less!!!!!” – users reported a changing relationship with beer, wine, and liquor.
An analysis of those posts, together with a remote study of individuals with obesity who reported using semaglutide and tirzepatide, found that the drugs decreased cravings and reduced alcohol consumption, according to a study by Virginia Tech researchers published inScientific Reports.
“These findings add to a growing literature that these medications may curb dangerous drinking habits,” said Warren Bickel, Virginia Tech Carilion Behavioral Health Research Professor at the Fralin Biomedical Research Institute at VTC and corresponding author.
Combing Reddit for users’ experiences
Scientists with the Fralin Biomedical Research Institute’s Addiction Recovery Research Center combined two different studies to build on existing research, including studies that showed the drugs were effective in reducing alcohol consumption in animal models.
The first was an analysis of more than 68 000 Reddit posts from 2009-23 that included terms linked to GLP-1 approved medications.
Semaglutide is a GLP-1 agonist, a class of drugs that reduce blood sugar and energy intake by mimicking the actions of hormones released after eating.
Among the keywords included in the search were Mounjaro, Wegovy, Ozempic, and Trulicity.
After cleaning the resulting data – such as eliminating comments with fewer than 100 characters – the set was narrowed to 33 609 posts from 14 595 unique users.
The study was unique in using Reddit to analyse the reported experience of thousands of users.
On examining alcohol-related discussions, researchers found that 962 individuals made 1580 alcohol-related posts.
Of those, 71.7% addressed reduced cravings, reduced usage, and other negative effects due to drinking.
In a second study, 153 participants who self-reported having obesity were recruited from various social media platforms.
Roughly a third of these participants represented the control group, a third were taking either a semaglutide injection or tablet, and a third were using tirzepatide.
Participants on semaglutide or tirzepatide reported drinking significantly fewer drinks, on average, than those in the control group who were not on any medication for diabetes or weight loss.
In addition, researchers found that both the average number of drinks and the odds of binge drinking were found to be significantly lower.
Results also found that the stimulative and sedative effects of alcohol intoxication are reduced when taking these medications.
“Participants reported drinking less, experienced fewer effects of alcohol when they did drink it, and decreased odds of binge drinking,” said Alexandra DiFeliceantonio, assistant professor at Fralin Biomedical Research Institute and one of the study’s co-authors.
Researchers believe theirs is the first published report following tirezepatide, sold under the brand name Mounjaro, which was approved in 2022 and is used for treatment of Type 2 diabetes and weight loss.
Why this matters
Case studies and reports in the popular press hint at the drugs’ unexpected side effect of reducing addictive behaviors, including the desire to consume alcohol.
The US Food and Drug Administration has approved only three medications to treat alcohol use disorder: disulfiram, naltrexone, and acamprosate.
They have shown only modest success, have poor compliance, and are underprescribed.
The authors suggest further randomized controlled trials to explore the therapeutic potential of GLP-1 agonists and GIP/GLP-1 combination drugs to treat alcohol use disorder, which affects 5.9% of individuals in the United States ages 12 and older.
In addition, the participants identified as mostly white and female, and further studies in more diverse populations are needed to examine sex and race differences.
“Although evidence supporting the use of these medications for alcohol use disorder is growing, the field still needs to learn considerably more about them, particularly in identifying the underlying mechanisms. We plan to contribute to that effort,” Bickel said.
The drugs are a promising development in the study of alcohol use disorder. Data from the National Survey on Drug Use and Health indicate 15.7 million people in the United States meet the criteria for the chronic, relapsing brain disorder that is a significant contributor to global mortality yet remains one of the most undertreated conditions, Bickel said.
Colourised electron micrograph image of a macrophage. Credit: NIH
Scientists have created a new treatment for traumatic brain injury (TBI). The new approach leverages macrophages, which can increase or decrease inflammation in response to infection and injury. The team attached “backpacks” containing anti-inflammatory molecules directly to the macrophages. These molecules kept the cells in an anti-inflammatory state when they arrived at the injury site in the brain, enabling them to reduce local inflammation and mitigate the damage caused. The research is reported in PNAS Nexus.
“Every year, millions of people suffer from a TBI, but there is currently no treatment beyond managing symptoms. We have applied our cellular backpack technology – which we previously used to improve macrophages’ inflammatory response to cancerous tumours – to deliver localised anti-inflammatory treatment in the brain, which helps mitigate the cascade of runaway inflammation that causes tissue damage and death in a human-relevant model,” said senior author Samir Mitragotri, PhD, in whose lab the research was performed.
Stopping a runaway inflammation train
There is currently no treatment for the damage caused to brain tissue during a traumatic brain injury (TBI), beyond managing a patient’s symptoms. One of the main drivers of TBI-caused damage is a runaway inflammatory cascade in the brain.
As cells die from the impact, they release a cocktail of pro-inflammatory cytokine molecules that attract immune cells to clean up the damage. But the same cytokine molecules can also disrupt the blood-brain barrier, which causes blood to leak into the brain. Blood accumulation in the brain causes swelling, impaired oxygen delivery, and increased inflammation, and creates a vicious cycle of bleeding and damage that drives even more cell death.
The Mitragotri lab saw an opportunity in this problem.
“It’s generally believed anti-inflammatory therapies can be effective for treating TBI, but so far, none of them have proven effective clinically. Our previous work with macrophages has shown us that we can use our backpack technology to effectively steer their behaviour when they arrive at the injury site. Since these cells are already active players in the body’s natural immune response to a TBI, we had a hunch we could augment that pre-existing biology to reduce the initial damage,” said co-first author Rick Liao, Ph.D., a Postdoctoral Fellow at the Wyss Institute and SEAS.
“Body, heal thyself”…with backpacks
Macrophages are very malleable cells and can “switch” between pro-inflammatory and anti-inflammatory states. While the team’s previous work in cancer had been focused on keeping macrophages in a pro-inflammatory state when they arrive at the inflammation-reducing microenvironment of a tumour, this new project would be trying to do the opposite: keep the macrophages “calm” in the inflammation-riddled setting of a brain injury.
To do so, they used a disc-shaped “backpack” they had previously designed to treat multiple sclerosis that contained layers of two anti-inflammatory molecules: dexamethasone, a steroid, and interleukin-4, a cytokine that encourages macrophages to adopt an anti-inflammatory state. They then incubated these microparticles with both human and pig macrophages in vitro and saw that the backpacks stably stuck to the cells without causing any negative effect. They also observed that application of their backpacks decreased the expression of pro-inflammatory biomarkers and increased the expression of anti-inflammatory biomarkers, retaining the pig macrophages in a healing state.
But to prove that this shift would work in the body, they had to test the backpack-bearing macrophages in vivo. They chose pigs as their model organism because their brains’ structures and responses to injury more closely mimic those of humans than mice.
“Probably our biggest challenge in this project was scaling up production to match what we needed to run the experiments. Our previous studies were done in rodents, which required about two million macrophages and four million backpacks administered per subject. For the porcine study, we needed 100 million macrophages and 200 million backpacks per subject – on the scale of what would be administered in humans – and lots of helping hands,” said co-first author Neha Kapate, PhD, a Postdoctoral Fellow at the Wyss Institute and SEAS.
Once they had generated enough backpack-wearing porcine macrophages, they infused them into the pigs’ bloodstreams four hours after a TBI. Seven days later, they analysed the animals’ brains. Pigs that had received the macrophage treatment showed a high concentration of the cells in the area immediately surrounding the injury site, their lesions were 56% smaller, and there was significantly less haemorrhaging than in untreated animals.
Local immune cells also displayed a lower amount of a pro-inflammatory activation marker called CD80, indicating that the macrophages had accomplished their damage control by reducing inflammation in the brain. Corroborating that data, the levels of two soluble biomarkers for inflammation in the blood and cerebrospinal fluid were lower in treated animals than in untreated animals. The macrophage treatment also did not cause any negative effects.
The team plans to conduct future studies that focus on elucidating exactly how their anti-inflammatory macrophage therapy affects the blood-brain barrier’s integrity to prevent bleeding, which could also hold promise for treating other conditions like hemorrhagic strokes.
“Macrophages’ susceptibility to their local environment has historically prevented scientists from taking full advantage of their immune-modulating capabilities. This impressive study describes a truly novel and potentially powerful macrophage-based therapy for treating the inflammation that is the root cause of so many human afflictions in an effective and non-invasive way that works with biology rather than against it,” said Wyss Founding Director Donald Ingber, MD, PhD.
