Colourised transmission electron micrograph of an HIV-1 virus particle (yellow/gold) budding from the plasma membrane of an infected H9 T cell (purple/green).
A team of scientists at the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg and the University of Regensburg has unveiled insights into how HIV-1 skilfully hijacks cellular machinery for its own survival. By dissecting the molecular interplay between the virus and its host, the researchers identified novel strategies that HIV-1 employs to ensure its replication while suppressing the host’s cellular defences. The study was published in the journal Nature Structural and Molecular Biology.
HIV-1, like other viruses, lacks the machinery to produce its own proteins and must rely on the host cell to translate its genetic instructions. After entering host cells, it seizes control of the translation process, which converts messenger ribonucleic acid (mRNA) into proteins. “In this study, we combined ribosome profiling, RNA sequencing and RNA structural probing to map the viral and host translational landscape and pausing during replication of the virus in unprecedented detail,” says corresponding author Neva Caliskan.
Cheat Codes of Viral Translation
One of the key findings was the discovery of previously unrecognized elements in HIV-1 RNA called upstream open reading frames (uORFs) and internal open reading frames (iORFs). These “hidden gene fragments” may play a crucial role in fine-tuning the production of viral proteins as well as the interaction with the host immune system. “For instance, uORFs and iORFs can act as regulators, ensuring precise timing and levels of protein synthesis”, explains Anuja Kibe, a postdoctoral researcher at the HIRI and first author of the study.
Another important discovery was an intricate RNA structure near the critical “frameshift site” in the viral genome. This frameshift site is essential for the virus to produce the correct proportions of two key proteins, Gag and Gag-Pol, which are necessary for assembling infectious particles and replication of HIV-1. The researchers demonstrated that this extended RNA fold not only promotes ribosome collisions upstream of the site (a mechanism that appears to regulate translation) but also maintains the frameshifting efficiency. “Our team also showed that targeting this RNA structure with antisense molecules could significantly reduce frameshift efficiency by nearly 40 percent, offering a promising new avenue for antiviral drug development”, reports Caliskan.
A Game of Priorities
Redmond Smyth, a former Helmholtz Young Investigator Group Leader at the HIRI and currently a group leader at the Centre National de Recherche Scientifique (CNRS) in Strasbourg, France, mentions, “Interestingly, our analysis revealed that, while HIV-1 mRNAs are translated efficiently throughout infection, the virus suppresses the protein production of the host, particularly at the translation initiation stage.” This allows HIV-1 to prioritise its own needs while effectively stalling the host defence mechanisms. Thus, the virus can manipulate the host cell machinery in ways that remain robust even under stress conditions.
More Than Traffic Jams
The researchers also observed that ribosomes collide at specific regions of the viral RNA, particularly upstream of the frameshift site. “These collisions are not accidental but are instead tightly regulated pauses that may influence how ribosomes interact with downstream RNA structures,” says Florian Erhard, study co-author and Chair of Computational Immunology at the University of Regensburg.
Overall, the study provides not only a detailed map of the translational landscape of HIV-1 infected cells but also a wealth of potential targets for therapeutic intervention. The identification of RNA structures and genetic elements critical for viral replication highlights new opportunities for the development of drugs aimed at disrupting these processes. “By understanding how the virus cleverly manipulates our cells, these discoveries will bring us closer to innovative treatments that could one day turn tables and outsmart the virus itself,” Caliskan adds.
AI image made with Gencraft using Quicknews’ prompts.
Quicknews takes a look at some of the big events and concerns that defined healthcare 2024, and looks into its crystal ball identify to new trends and emerging opportunities from various news and opinion pieces. There’s a lot going on right now: the battle to make universal healthcare a reality for South Africans, growing noncommunicable diseases and new technologies and treatments – plus some hope in the fight against HIV and certain other diseases.
1. The uncertainty over NHI will continue
For South Africa, the biggest event in healthcare was the signing into law of the National Health Insurance (NHI) by President Ramaphosa in May 2024, right before the elections. This occurred in the face of stiff opposition from many healthcare associations. It has since been bogged down in legal battles, with a section governing the Certificate of Need to practice recently struck down by the High Court as it infringed on at least six constitutional rights.
Much uncertainty around the NHI has been expressed by various organisation such as the Health Funders Association (HFA). Potential pitfalls and also benefits and opportunities have been highlighted. But the biggest obstacle of all is the sheer cost of the project, estimated at some R1.3 trillion. This would need massive tax increases to fund it – an unworkable solution which would see an extra R37 000 in payroll tax. Modest economic growth of around 1.5% is expected for South Africa in 2025, but is nowhere near creating enough surplus wealth to match the national healthcare of a country like Japan. And yet, amidst all the uncertainty, the healthcare sector is expected to do well in 2025.
Whether the Government of National Unity (GNU) will be able to hammer out a workable path forward for NHI remains an open question, with various parties at loggerheads over its implementation. Public–private partnerships are preferred by the DA and groups such as Solidarity, but whether the fragile GNU will last long enough for a compromise remains anybody’s guess.
It is reported that latest NHI proposal from the ANC includes forcing medical aid schemes to lower their prices by competing with government – although Health Minister Aaron Motsoaledi has dismissed these reports. In any case, medical aid schemes are already increasing their rates as healthcare costs continue to rise in what is an inexorable global trend – fuelled in large part by ageing populations and increases in noncommunicable diseases.
Further on the horizon, there are a host of experimental drugs undergoing testing for obesity treatment, according to a review published in Nature. While GLP-1 remains a target for many new drugs, others focus on gut hormones involved in appetite: GIP-1, glucagon, PYY and amylin. There are 5 new drugs in Phase 3 trials, expected variously to finish between 2025 and 2027, 10 drugs in Phase 2 clinical trials and 18 in Phase 1. Some are also finding applications beside obesity. The GLP-1 agonist survodutide, for example have received FDA approval not for obesity but for liver fibrosis.
With steadily increasing rates of overweight/obesity and disorders associated with them, this will continue to be a prominent research area. In the US, where the health costs of poor diet match what consumers spend on groceries, ‘food as medicine’ has become a major buzzword as companies strive to deliver healthy nutritional solutions. Retailers are providing much of the push, and South Africa is no exception. Medical aid scheme benefits are giving way to initiatives such as Pick n Pay’s Live Well Club, which simply offers triple Smart Shopper points to members who sign up.
Another promising approach to the obesity fight is precision medicine, which factors in many data about the patient to identify the best interventions. This could include detailed study of energy balance regulation, helping to select the right antiobesity medication based on actionable behavioural and phsyiologic traits. Genotyping, multi-omics, and big data analysis are growing fields that might also uncover additional signatures or phenotypes better responsive to certain interventions.
3. AI tools become the norm
Wearable health monitoring technology has gone from the lab to commonly available consumer products. Continued innovation in this field will lead to cheaper, more accurate devices with greater functionality. Smart rings, microneedle patches and even health monitoring using Bluetooth earphones such as Apple’s Airpods show how these devices are becoming smaller and more discrete. But health insurance schemes remain unconvinced as to their benefits.
After making a huge splash in 2024 as it rapidly evolved, AI technology is now maturing and entering a consolidation phase. Already, its use has become commonplace in many areas: the image at the top of the article is AI-generated, although it took a few attempts with the doctors exhibiting polydactyly and AI choosing to write “20215” instead of “2025”. An emerging area is to use AI in patient phenotyping (classifying patients based on biological, behavioural, or genetic attributes) and digital twins (virtual simulations of individual patients), enabling precision medicine. Digital twins for example, can serve as a “placebo” in a trial of a new treatment, as is being investigated in ALS research.
Rather than replacing human doctors, it is likely that AI’s key application is reducing lowering workforce costs, a major component of healthcare costs. Chatbots, for example, could engage with patients and help them navigate the healthcare system. Other AI application include tools to speed up and improve diagnosis, eg in radiology, and aiding communication within the healthcare system by helping come up with and structure notes.
4. Emerging solutions to labour shortages
Given the long lead times to recruit and train healthcare workers, 2025 will not likely see any change to the massive shortages of all positions from nurses to specialists.
At the same time, public healthcare has seen freezes on hiring resulting in the paradoxical situation of unemployed junior doctors in a country desperately in need of more doctors – 800 at the start of 2024 were without posts. The DA has tabled a Bill to amend the Health Professions Act at would allow private healthcare to recruit interns and those doing community service. Critics have pointed out that it would exacerbate the existing public–private healthcare gap.
But there are some welcome developments: thanks to a five-year plan from the Department of Health, family physicians in SA are finally going to get their chance to shine and address many problems in healthcare delivery. These ‘super generalists’ are equipped with a four-year specialisation and are set to take up roles as clinical managers, leading multi-disciplinary district hospital teams.
Less obvious is where the country will be able to secure enough nurses to meet its needs. The main challenge is that nurses, especially specialist nurses, are ageing – and it’s not clear where their replacements are coming from. In the next 15 years, some 48% of the country’s nurses are set to retire. Coupled with that is the general consensus that the new nursing training curriculum is a flop: the old one, from 1987 to 2020, produced nurses with well-rounded skills, says Simon Hlungwani, president of the Democratic Nursing Organisation of South Africa (Denosa). There’s also a skills bottleneck: institutions like Baragwanath used to cater for 300 students at a time, now they are only approved to handle 80. The drive for recruitment will also have to be accompanied by some serious educational reform to get back on track.
5. Progress against many diseases
Sub-Saharan Africa continues to drive declines in new HIV infections. Lifetime odds of getting HIV have fallen by 60% since the 1995 peak. It also saw the largest decrease in population without a suppressed level of HIV (PUV), from 19.7 million people in 2003 to 11.3 million people in 2021. While there is a slowing in the increase of population living with HIV, it is predicted to peak by 2039 at 44.4 million people globally. But the UNAIDS HIV targets for 2030 are unlikely to be met.
As human papillomavirus (HPV) vaccination programmes continue, cervical cancer deaths in young women are plummeting, a trend which is certain to continue.
A ‘new’ respiratory virus currently circulating in China will fortunately not be the next COVID. Unlike SARS-CoV-2, human metapneumovirus (HMPV) has been around for decades, and only causes a few days of mild illness, with bed rest and fluids as the primary treatment. The virus has limited pandemic potential, according to experts.
The Institute for Health Metrics and Evaluation (IHME) has published a new study in The Lancet HIV journal that revealed significant progress in the global fight against HIV/AIDS, alongside a stark warning that current trends indicate the world is not on track to meet the ambitious UNAIDS 2030 targets.
The research, which analysed the global, regional, and national burden of HIV/AIDS among 204 countries and territories from 1990 to 2021 and forecasted trends to 2050, highlighted a mixed landscape of achievements and challenges in the battle against this global epidemic.
Between 2010 and 2021, new HIV infections decreased from 2.1 million to 1.7 million, and HIV-related deaths decreased from 1.2 million to 718 000. Despite this progress, researchers found regional variation in the HIV response and forecast the world is not on track to meet UNAIDS 2030 targets to cut new HIV infections and AIDS-related deaths by 90%.
Sub-Saharan Africa leads the world in cutting new HIV infections and deaths from the disease
The global decline in HIV incidence is largely driven by sub-Saharan Africa, where the likelihood of getting HIV over a lifetime has fallen by 60% since its peak in 1995. This region also achieved the largest decrease in population without a suppressed level of HIV (PUV), from 19.7 million people in 2003 to 11.3 million people in 2021.
In contrast, the lifetime probability of HIV acquisition increased from 0.4% to 2.8% between 1995 and 2021, while PUV rose from 310 000 people to 680 000 people between 2003 and 2021 in Central Europe, Eastern Europe, and Central Asia.
“The world has made remarkable global progress to significantly reduce the number of new HIV infections and lives lost to the disease, yet there are remaining challenges to overcome,” said Dr. Hmwe Kyu, IHME Associate Professor and study author. “More than a million people acquire a new HIV infection each year and, of the 40 million people living with HIV, a quarter are not receiving treatment,” she added.
Despite progress, UNAIDS’s HIV infection reduction and AIDS-related deaths 2030 targets won’t be met
Although substantial progress has been made against HIV incidence and AIDS-related mortality, the world is not on target to meet the UN’s 2030 targets to reduce new HIV infections and AIDS-related deaths by 90%.
The number of people living with HIV is expected to peak at 44.4 million by 2039, followed by a gradual decrease to 43.4 million people by 2050.
“The global community must make sustained and substantive efforts to sharpen the focus on prevention, optimize access to antiretroviral therapy, and make HIV testing widely available to achieve prompt diagnosis and linkage to care,” said Dr. Kyu.
New cases of HIV, and deaths associated with the disease, are expected to continue to decrease globally. However, long-term increases have been forecast in North Africa and the Middle East, where only 67% of people living with HIV are aware of their status, 50% access ART, and 45% are virally suppressed.
“Although new HIV infections and HIV-related mortality have fallen globally, they are increasing in several nations and regions. Our analysis is designed to inform countries’ sustained response to HIV that includes expanded access to lifesaving antiretroviral therapy (ART), effective prevention options, and innovative care models,” said Austin Carter, IHME Research Scientist.
The study authors set a series of recommendations to sustain and invigorate the global HIV response, including the strengthening of the US President’s Emergency Plan for AIDS Relief (PEPFAR) and other similar public health programs dedicated to HIV control, as well as the expansion of prevention services, with a multitude of existing and emerging technologies. Additionally, interventions and care delivery models that work must be studied and implemented effectively and equitably, with special emphasis on measuring progress and addressing remaining gaps in our collective goal of ending the HIV epidemic.
The findings and recommendations from the new study by the GBD 2021 HIV collaborators serve as a call to action for governments, health care providers, and the global community to renew their commitment to ending the HIV epidemic. Only through sustained, comprehensive, and equitable efforts will the world be able to achieve the UNAIDS 2030 targets and ultimately eradicate HIV/AIDS as a public health threat.
A University of Minnesota Medical School research team has found that giving iron supplements to children living with human immunodeficiency virus (HIV) in sub-Saharan Africa could be an important first step in optimising brain development.
The study, published in Lancet HIV, demonstrates that iron, while often withheld from children with HIV due to fear of increasing infection risk, is in fact beneficial. This finding paves the way for future research examining iron’s role in neurodevelopmental outcomes in children with HIV.
“With the success and widespread availability of antiretroviral therapy (ART), children with HIV in sub-Saharan Africa are living longer, and optimising their brain development is a new public health imperative,” said Sarah Cusick, PhD, associate professor at the U of M Medical School and a member of the Masonic Institute for the Developing Brain.
Between May 2018 and November 2019, researchers enrolled 200 children with HIV and anaemia who had received ART for at least six months. The study participants were randomly chosen to receive either iron supplements or a placebo for three months. Children who received iron had higher haemoglobin concentrations and better markers of iron nutrition than those who received the placebo. There also was no evidence of increased risk of infection.
According to Dr Cusick, further research is needed to assess brain development and infection risk over a longer period of time.
A therapy showing promise to help control tuberculosis (TB) does not interfere with combined antiretroviral therapy (cART), according to research by Texas Biomedical Research Institute (Texas Biomed) which was recently published in JCI Insight.
“This is an important hurdle that this host-directed therapy had to clear in order to help patients battling both HIV and TB,” said study leader Professor Smriti Mehra, PhD of Texas Biomed.
TB is responsible for more than 1.3 million deaths worldwide every year. Dr. Mehra and her team have been investigating a therapy currently used in cancer as a potential treatment for patients with drug-resistant TB and/or comorbid HIV. While many cases of TB can be controlled with months of antibiotics, the infection can return in people who are immunocompromised as a result of HIV. Now that cART is so effective at controlling HIV, a resurging TB infection can often be deadly to those individuals.
Dr Mehra is studying a host-directed therapy that blocks or inhibits an immune system protein naturally found in the body. The protein, called IDO (short for Indoleamine-2,3-dioxygenase), normally suppresses the immune system, preventing it from causing excessive inflammation and organ damage. Inhibiting IDO for short intervals of time has led to more successful cancer treatments. Dr. Mehra’s team has previously shown the same approach improves control of TB in conjunction with antibiotics.
This current study in nonhuman primates with both TB and simian immunodeficiency virus, the nonhuman primate version of HIV, showed the IDO inhibitor does not interfere with cART.
Researchers compare the impacts of cART by itself versus cART plus the IDO inhibitor in lung tissue of nonhuman primates with both TB and SIV. Left: Following just cART, significantly more IDO is detected in pink. Right: With the IDO inhibitor and cART, immune cells recruited to fight bacteria are observed inside the granuloma, a hallmark structure of TB. Specifically, CD4+ T cells are in green and CD68 proteins expressed by macrophages are in red.
“There was no increase in viral load in animals given cART and the IDO inhibitor, compared with animals only given cART, proving the inhibitor is safe to give to patients with HIV,” Dr. Mehra said.
Now that the researchers have shown the inhibitor works well in conjunction with TB antibiotics and with cART separately, they plan to study how it performs when given in conjunction with both antibiotics and cART together. This treatment regimen is standard for patients with both HIV and active TB. Dr. Mehra said that longer-term studies are also needed to confirm there are no unintended side effects.
The IDO inhibitor is already FDA-approved for use in patients with cancer, which shortens the path to potential approval for patients with TB/HIV when compared with developing a brand-new drug.
The African Centre for Disease Control and World Health Organization have raised the alarm following a drastic uptick in mpox cases. This surge is being driven by a new strain of the virus. Elri Voigt reports about what we know so far and potential implications for South Africa.
Mpox, a viral illness first identified in Africa in 1970, made headlines in 2022 when it spread across the globe for the first time. Since then, the outbreak has evolved, with multiple strains of the virus circulating in different countries. A new strain, known as clade Ib, first discovered in the Democratic of the Republic of Congo (DRC), is responsible for much of the most recent surge in mpox cases.
These recent developments are complex, and the situation is likely to change. This was the common theme of a special session on the mpox outbreak during the World Health Organization (WHO) Regional Committee for Africa meeting at the end of August. This session took place two weeks after the WHO declared the outbreak to be a Public Health Emergency of International Concern.
“We don’t have one outbreak. We have multiple outbreaks in one,” Dr Jean Kaseya, the Director General of the African Centre for Disease Control (CDC) remarked.
These outbreaks are caused by different clades of the mpox virus. Clades are a classification system based on the genetic similarities between different strains of a virus, explained Professor Tulio de Oliveira, Director of the Centre for Epidemic Response and Innovation (CERI) at Stellenbosch University (SU). “So, what it means is that when we see a genetic change [in a virus] that’s really visible and that may have impacted it, normally we call it a different clade or genotype or variant,” he said.
This is similar to classifying different strains of SARS-CoV-2 as variants, Dr Duduzile Ndwandwe, a molecular biologist working for Cochrane South Africa, an intramural research unit within the South African Medical Research Council, told Spotlight.
She explained that the different mpox clades and sub-clades have mutated so they have genetic differences but still fall under the umbrella of mpox.
“In a nutshell…it’s just talking about the differences in the genome sequence of the virus, how many mutations [it has] or how big the mutations are in that virus’s strain of mpox,” she said.
‘Jump in evolution’
Dr Aida Sivro, senior scientist at the Centre for the AIDS programme of Research in South Africa (CAPRISA), in 2022 told Spotlight that there are two clades of the mpox virus, which were then referred to as the Central African Clade (clade I) and the West African Clade (clade II).
Since then, clade I went through a big jump in evolution and a sub-clade emerged in the DRC, now called clade Ib, De Oliveira told Spotlight. The previous outbreak in 2022 was mostly driven by another sub-clade called clade IIb.
To further complicate matters, there’s a third strain of the virus also circulating – clade Ia.
At the moment, the DRC accounts for about 90% of mpox cases in the African Region, according to Dr Fiona Braka, the Emergency Response Manager for WHO’s AFRO region. She explained that right now the situation is not fully understood because a lack of diagnostics and testing capabilities is limiting understanding of the true burden of disease.
What we do know, she said, is that there are two distinct outbreaks in the DRC. Based on the information currently available, clade Ia is circulating in regions in the country where mpox is considered endemic and affecting mostly children. While clade Ib is spreading mostly among adults in the eastern provinces of South Kivu and North Kivu.
The clade Ib strain has since spread from the DRC to neighbouring countries Burundi, Rwanda, Uganda and Kenya, according to Braka. Sweden and Thailand have also identified one case each.
As of 1 September, the WHO reported that there have been 3 751 confirmed cases of mpox and 32 deaths across 14 countries in African in 2024 alone. But there are many more suspected cases of mpox that have not been tested.
Implications for South Africa
De Oliveira said at this point, South Africa shouldn’t be overly concerned about mpox, but it should be alert. The best way to do this is to make sure the public know what the symptoms are so they can present for diagnosis and treatment if they suspect they have the virus.
In a similar vein, Ndwandwe said the public shouldn’t panic, but we as a country need to remain vigilant. She added that because clade Ib is spreading on the African continent, there is a risk of it spreading to South Africa through cross-border travel, making it a public health concern.
This year, 24 cases of mpox have been reported in South Africa. Three people have died, while 19 have recovered. Two people are still considered to have active disease, with the most recent case identified in early August.
But this doesn’t necessarily mean there aren’t more cases of mpox in the country. “What we do suspect is that we may have milder cases that are actually not reported,” Nevashan Govender, the operation manager of the Emergency Operations Center at the National Institute for Communicable Diseases (NICD) told Spotlight.
He said so far, all the cases in the country have been caused by clade IIb and no cases of clade Ib have been identified.
A polymerase-chain-reaction (PCR) test is the gold standard test used to determine whether someone has mpox. But genome sequencing would need to be done to identify what clade they have.
Lots of unknowns around new strain
At the moment, there are a lot of unknowns around clade Ib.
What is of concern, according to Braka is the severity of disease seen especially in people who are immunocompromised and in pregnant women and children. Ndwandwe added to this and said there is a concern that clade Ib has higher fatality rates than clade IIb.
De Oliveira cautioned against jumping to conclusions about the severity of this new clade without sufficient data. He said we don’t know for sure yet if clade Ib is causing more severe disease than IIb. What we do know from mpox in general, he said, is that when someone is immunocompromised in some way, they tend to develop more severe symptoms.
Govender echoed De Oliveira’s caution that we don’t yet know enough about clade Ib to say definitively if it is for example more transmissible than other clades
“It’s not to say that it isn’t [more transmissible], but there is just not a lot of evidence stating that it is absolutely true…There’s a lot of knowledge and information gaps,” he said.
The NICD in a recent update also stressed that there are a lot of unknowns about this new strain. It added: “South Africa continues to prioritise enhanced surveillance and raising awareness for mpox.”
The state of vaccines and treatment for mpox
Spotlight reported previously that the smallpox vaccine, which hasn’t been routinely administered in South Africa since the 1980s when smallpox was eradicated, is thought to offer some degree of protection against mpox. However, it’s difficult to predict just how much protection the smallpox vaccine would provide, Sirvo told Spotlight for that previous article.
There are currently three vaccines against mpox that have been approved in some countries, a spokesperson from the vaccine alliance Gavi told Spotlight. These are LC16m8, JYNNEOS and ACAM2000.
LC16m8 is a third-generation small pox vaccine manufactured by KM Biologics. According to WHO, from 2022 it had mainly been used in Japan.
The JYNNEOS vaccine is a third-generation smallpox vaccine, manufactured by Bavarian Nordic, Ndwandwe said, and it was used during the outbreak in 2022. She added that this vaccine is considered the preferred option due to its safety profile and targeted protection against mpox.
ACAM2000 is a second-generation vaccine for smallpox and manufactured by Emergent BioSolutions. But it was only approved by the FDA for use in those at high risk for mpox at the end of August this year. It was not widely used during the 2022 outbreak but was available in some places under a compassionate use protocol (a means of providing medicines or vaccines that have not yet been registered).
In 2022, the Centre for Disease Control (CDC) recommended that JYNNEOS be used as the primary vaccine against mpox because it was associated with fewer side effects than ACAM2000.
While these vaccines exist, it doesn’t mean everyone can access them easily. Countries on the African continent have so far relied on vaccine donations facilitated by the WHO, with an initial 10 000 doses expected to arrive in Africa sometime this month.
Vaccine manufacturers KM Biologics and Bavarian Nordic have submitted proposals to the WHO for emergency use listing (EUL), according to WHO Director-General Dr Tedros Adhanom Ghebreyesus. He added this will allow UNICEF and the vaccine alliance GAVI to buy the vaccines to supply to countries that haven’t issued their own national regulatory approval yet.
The treatment options for mpox are also limited. According to this WHO factsheet on mpox, some antivirals have received emergency use authorisation in some countries and are being evaluated in clinical trials. However, so far there is no proven effective antiviral treatment for mpox.
Tecovirimat, which was approved to treat smallpox, is one of these antivirals being evaluated. According to the CDC, studies in animals have shown the antiviral might help treat mpox but it is still considered an investigational drug for mpox. The drug has been used in some cases of severe mpox.
When asked about this, Ndwandwe agreed more research needs to be conducted to fully understand the evidence around using Tecovirimat. “But what we know now is that the fact that it was authorised for compassionate use, there is some benefit to using that treatment, given that there isn’t any other [treatment,” she said.
Mpox vaccine and treatment availability in South Africa
According to De Oliveira, a small batch of vaccines against mpox and an antiviral drug were made available to South Africa through donations during the outbreak earlier this year.
But the country would need more vaccines if cases increase to protect those at risk for severe disease.
At the moment, South Africa does not have access to any mpox vaccines and has asked for a donation of 40 000 vaccine doses, Foster Mohale, spokesperson for the health department told Spotlight. The country has requested the JYNNEOS vaccine, based on the recommendation by the National Advisory Group on Immunisation.
He added that South Africa’s request to its international partners and the WHO is ongoing support with access to tecovirimat should the need increase. He also requested the WHO’s assistance in procuring the 40 000 vaccine doses to vaccinate high-risk groups if mpox cases increase.
When asked if the department will be entirely reliant on donations of mpox vaccines or would seek to procure its own if cases increase, Mohale said it depends. “South Africa has been in communication with the vaccine manufacturer, Bavarian Nordic, and will consider procurement if needed,” he added.
Because there is a shortage of mpox vaccines and treatment and uncertainty about the sustainability of donated supplies, Ndwandwe said: “Our best defence at this point in time is to prevent [the spread of mpox cases] as much as possible and detect the cases as they start, early on.”
Symptoms of mpox
Govender said the NICD is urging people not to panic but to stay informed on the signs and symptoms of mpox using some of the accurate information available from either the National Department of Health or the NICD.
“The first line of defence for any public health emergency and outbreak comes from when people take initiative to protect themselves,” he said.
Mpox, which is spread by close contact, either household or sexual contact, with someone who has the virus, could initially manifest in flu-like symptoms or the characteristic mpox rash. These include a fever, sore throat, muscle aches, headaches and swollen lymph nodes, according to the WHO factsheet on mpox. The rash starts flat and then becomes a blister filled with fluid, which eventually dries and falls off. The rash can occur on someone’s palms or soles of their feet, face, mouth and throat and sometimes the genital areas.
Children, pregnant women and those who are immunocompromised are most at risk for developing severe disease or dying, the factsheet stated. This includes people living with HIV whose viral load is not well controlled.
Mpox is a virus and as with all viral infections it’s the immune system that fights it off, Ndwandwe explained. However, if someone is immunocompromised, so has a weakened immune system, there is a greater chance that the mpox virus will overtake their immune system and cause severe disease.
This is one of the reasons why we would be concerned about the disease in South Africa, Professor Helen Rees, the Co-Chair of the Incident Management Team (IMT) on mpox, previously told eNCA.
“We have many people living with HIV in the country, many of whom are on antiretroviral therapy, their immune system is good. But we have many others, who don’t know what their status is and might be vulnerable to severe mpox,” she said.
Photo by Miguel Á. Padriñán: https://www.pexels.com/photo/syringe-and-pills-on-blue-background-3936368/
By Nthusang Lefafa
Despite some improvement over the past three years, the North West province continues to experience medicine shortages, according to a survey by a community clinic monitoring initiative. We unpack the latest findings and ask why shortages persist in the province.
Some people in need of HIV or tuberculosis (TB) medicines were sent home empty handed after visiting clinics in the North West. This is according to the latest survey of public healthcare services in the province published by community-led clinic monitoring group Ritshidze. The survey data was collected in April and May this year.
Of the roughly 490 000 people living with HIV in North West, around 380 000 (77%) are on antiretroviral treatment, according to figures from Thembisa, the leading mathematical model of HIV in South Africa. Antiretroviral treatment is recommended for everyone living with the virus.
According to Ritshidze, besides HIV and TB medicines, other commonly reported stockouts at clinic-level include pain medicines (such as Paracetamol and Ibuprofen), cardiac medicines (such as Aspirin), contraceptives, dry stock (gauze, bandages, needles), maternal health medicines, psychiatric medicines, and different vaccines.
Out of the 72 facilities surveyed in the province, medicine stockouts lasting one to three months were reported at 20 and stockouts lasting three to six months were reported at six.
‘Failed to comply’
The North West health department, according to Ritshidze, has failed to comply with national guidelines recommending that people living with HIV should be provided with a three or more month supply of antiretrovirals at a time. They found that 71% of people surveyed in 2024 received antiretroviral refills of three to six months – in each of the previous three years this number was below 30%. There was large differences between districts, with 97% of people surveyed in Bojanala district reporting getting a 3 month supply of ARVs — compared to 37% in Dr Kenneth Kaunda.
Giving people longer antiretroviral refills like this means people do not have to visit health facilities as often to collect their medicines.
Various factors influence giving more people longer antiretroviral refills, Tebogo Lekgethwane, Director of Media and Communications in the province’s health department, told Spotlight.
A crucial factor, he said, is that patients must have a good track record of collecting their medication as well as a history of a documented undetectable viral load. “There’s therefore a criteria for multi-month supply which includes the fact that patients should have been on treatment for six months, they are compliant and clinically stable,” said Lekgethwane.
No “crisis” of medicine shortages
While the year-on-year comparisons should not be overinterpreted – Ritshidze themselves advise caution – the numbers nevertheless provide some indication that when it comes to medicines stockouts things are trending in the right direction. The total number of stockouts in the province reported to Ritshidze plunged from 895 in 2021 to 148 in 2024 – over the same period stockouts of HIV medicines went from 115 to 19 and stockouts of TB medicines from 28 to 7.
Lekgethwane was at pains to point out that Ritshidze’s findings do not necessarily represent the actual picture of the entire province. He said that the department believes that the Ritshidze report is subjective and relies on isolated incidents. These incidents, Lekgethwane said, are often quickly addressed.
“The current provincial medicine availability report shows that medicine availability has stabilised above 80%. As at the end of June 2024, ARV stock was at 89.5%, Expanded Programme on Immunisation and Contraceptives remained above 90%, TB treatment at 79%, Oncology treatment at 81.7% and Diabetes Mellitus at 85.8%. Therefore the province does not have a crisis of medicine shortages,” he said.
Asked what exactly these percentages mean, Lekgethwane said that it indicates the actual medicines stock available in the province in relation to what is required.
A pharmacy expert consulted by Spotlight further explained that the percentage indicates the percentage of medicines on a list or in a class that is available in the province.
The way these numbers are tracked is somewhat tricky. Firstly, if a clinic is supposed to have 10 different HIV medicines in stock, but they only have 8 in stock, then its HIV medicines availability would be at 80% (having a single pack of a medicine counts as having it in stock). When many facilities are considered together, as with an entire province like North West, the key indicator looks at what percentage of those facilities have medicines availability above 90%. We thus understand the figures shared by Lekgethwane to mean that 89.5% of facilities, depots and so on in the province have HIV medicines availability above 90%.
Catching up with payments
Past medicine shortages in the province were partly attributed to companies ceasing delivery of medicine due to non-payment of invoices. While the North West health department was under National Department of Health administration in 2020, the offices at the Mmabatho Medical Depot was raided. The search uncovered a number of unpaid invoices worth millions, some dating back to 2014. One unpaid invoice was for more than R16 million.
Bolstered by a Pharmaceutical Intervention Team to address medicine shortages, Lekgethwane said the department’s payments system is now in top shape.
“Payment of suppliers has remained a priority and the finance unit has assisted the team by making good progress on payments of supplier accounts. The unit continues to investigate and intervene when suppliers indicate their account status to the pharmacies.
“This has led to an increased number of deliveries from suppliers to the depot and increased direct deliveries to pharmacies from contracted companies as well as deliveries of main orders, allocation of orders and emergency orders from the depot to the pharmacies,” he said.
“The Department can confidently confirm that the financial management of pharmaceuticals has been improved resulting in 97% of 2024/2025 accruals being paid and remaining with only two accounts that are on hold. The two accounts that are on hold will only be paid once their compliance requirements are sorted,” said Lekgethwane.
He said that the intervention team has the capacity to assess and intervene, in among others, pharmaceutical supply chain issues, system effectiveness, distribution and delivery processes, storage capacity, human resource capacity and safety issues.
Lekgethwane said the team’s first priority was to assess the Mmabatho Medical Depot before moving onto pharmacies in hospitals and clinics across the province.
Getting medicines to rural areas
While Ritshidze also raised concern around transportation for the delivery of medicines, the department said transportation has never been a challenge.
“There are contracted service providers who deliver to the Mmabatho Medical Depot and the depot delivers to hospitals. Clinics receive their medicine from their referral hospital,” said Lekgethwane.
“However, the department is currently implementing the bulk pharmacies for districts to bring medicines closer to facilities”, he added. A bulk pharmacy is a medicine storage facility which serves as a medical depot. It is situated in the districts and helps with bringing medicines closer to rural areas so that medicines do not have to be transported from major towns.
In this regard, Lekgethwane said the Dr Kenneth District Bulk Pharmacy was recently opened and soon the General De la Rey Bulk Pharmacy will open.
He said the department is confident that the use of these bulk pharmacies will improve medicine storage and distribution capacity.
Shortage of pharmacists and pharmacy assistants
The Ritshidze report found that only 9% of surveyed facilities had a pharmacist and only 18% had a pharmacist assistant. Government regulations state that either pharmacists or pharmacy assistants should be responsible for stock receiving orders and updating the stock visibility system. However, Ritshidze found that enrolled nurses, enrolled nurse assistants, facility managers, and even cleaners acted in that capacity at some clinics.
The province has a 6% vacancy rate for pharmacists while 342 are currently employed, according to the 2024/2025 health department annual performance plan tabled in the North West Provincial Legislature earlier this month. The plan states that the department’s organisational structure makes provision for 10 pharmacists to be appointed in the province for every 100 000 uninsured individuals.
The DA’s Hendriette van Huyssteen says there is a challenge of pharmacists and pharmacy assistants where there are clusters of less than 10 000 uninsured individuals (where one pharmacist would be allocated for 10 000 uninsured individuals) and the clinics servicing them are far removed from one another.
“With the NHI [National Health Insurance] being signed into law, the number of pharmacists will become only a greater challenge. The cost per pharmacist employee stands at R765 000.00 per annum. It is unclear as to where the funding would come from for the remuneration of the additional pharmacists needed under the NHI, as even the NHI Act is unclear in this regard,” she said.
Notwithstanding the issue of budget constraints, the training of more pharmaceutical staff is integral to having fully functional health systems, said Professor Andrew Robinson. He is a deputy dean in the Faculty of Health Sciences at North West University (NWU). He was previously a deputy director general in the North West health department.
“To improve the pharmaceutical skills in the province, the NWU must ensure it aligns its pharmacy training to address the skill needs of the provincial health department to ensure equitable health service delivery to all, which is necessary for successful implementation of the NHI,” he said.
Colourised scanning electron micrograph of HIV (yellow) infecting a human T9 cell (blue). Credit: NIH
An experimental drug originally developed to treat cancer may help clear HIV from infected cells in the brain, according to a new study published in the journal Brain. For the first time, researchers at Tulane University found that a cancer drug significantly reduced levels of SIV, the nonhuman primate equivalent of HIV, in the brain by targeting and depleting certain immune cells that harbour the virus.
This discovery marks a significant step toward eliminating HIV from hard-to-reach reservoirs where the virus evades otherwise effective treatment.
“This research is an important step in tackling brain-related issues caused by HIV, which still affect people even when they are on effective HIV medication,” said lead study author Woong-Ki Kim, PhD, associate director for research at Tulane National Primate Research Center. “By specifically targeting the infected cells in the brain, we may be able to clear the virus from these hidden areas, which has been a major challenge in HIV treatment.”
Antiretroviral therapy (ART) is an essential component of successful HIV treatment, but the virus persists in “viral reservoirs” in the brain, liver, and lymph nodes, where it remains out of reach of ART.
The brain has been a particularly challenging area for treatment due to the blood-brain barrier preventing treatments from reaching the virus. In addition, macrophages are extremely long-lived, making them difficult to eradicate once they become infected.
Infection of macrophages is thought to contribute to neurocognitive dysfunction, experienced by nearly half of those living with HIV. Eradicating the virus from the brain is critical for comprehensive HIV treatment and could significantly improve the quality of life for those with HIV-related neurocognitive problems.
Researchers focused on macrophages, a type of white blood cell that harbours HIV in the brain. By using a small molecule inhibitor to block a receptor that increases in HIV-infected macrophages, the team successfully reduced the viral load in the brain. This approach essentially cleared the virus from brain tissue, providing a potential new treatment avenue for HIV.
The small molecule inhibitor used, BLZ945, has previously been studied for therapeutic use in amyotrophic lateral sclerosis (ALS) and brain cancer, but never before in the context of clearing HIV from the brain.
The study, which took place at the Tulane National Primate Research Center, utilised three groups to model human HIV infection and treatment: an untreated control group, and two groups treated with either a low or high dose of the small molecule inhibitor for 30 days. The high-dose treatment lead to a notable reduction in cells expressing HIV receptor sites, as well as a 95-99% decrease in viral DNA loads in the brain .
In addition to reducing viral loads, the treatment did not significantly impact microglia, the brain’s resident immune cells, which are essential for maintaining a healthy neuroimmune environment. It also did not show signs of liver toxicity at the doses tested.
The next step for the research team is to test this therapy in conjunction with ART to assess its efficacy in a combined treatment approach. This could pave the way for more comprehensive strategies to eradicate HIV from the body entirely.
One of the biggest stories in HIV in the last year was that a class of medicines called statins could help reduce cardiovascular disease in people living with the virus. In response, treatment guidelines in the United States were quickly updated, but the picture is more complicated in South Africa. Spotlight’s Elri Voigt explores why the case for widespread use of statins by people living with HIV is less compelling in South Africa than in some other countries.
People living with HIV, provided they are stable on antiretroviral therapy, are affected by the same diseases as those who don’t have HIV, including cardiovascular disease, says Professor Mpiko Ntsekhe, head of Cardiology at Groote Schuur Hospital in Cape Town.
The key difference, he says, is that although both groups of people get the same spectrum of diseases, people living with HIV get those diseases more frequently and earlier. One way to think about this, he explains, is to imagine twins who are identical in every way except one is living with HIV. The twin living with HIV is more likely to get cardiovascular disease than the other twin.
And these differences can be substantial. Current evidence shows that people living with HIV have a twofold increased risk of developing cardiovascular disease compared to people not living with HIV, says Professor Hans Strijdom. He is the Head of the Division of Medical Physiology and Deputy Director of the Centre for Cardio-Metabolic Research in Africa (CARMA) at Stellenbosch University. The cardiovascular risk attributable to HIV, Strijdom adds, is now believed to be equivalent to that posed by traditional risk factors such as smoking. This prompted an editorial in 2018 in one of the top cardiovascular journals, Circulation, advocating for HIV to be recognised as a major cardiovascular risk factor.
He explains that people living with HIV who are stable on treatment are living longer, making them susceptible to the normal risk posed by older age. They also have “modifiable risk factors, in other words lifestyle risk factors”, like a higher smoking and alcohol use incidence, as well as increasing rates of being overweight and obesity. Strijdom says that living with HIV, even when someone is stable on treatment, causes low-grade inflammation, which over time increases a person’s risk for cardiovascular disease. “That all in combination are the current theories [of] why we think that they have a bigger risk of cardiovascular disease,” he says.
Important study findings
Arguably, the biggest news from last year’s International AIDS Society (IAS) Conference in Australia was findings from a study on heart disease in people living with HIV. The trial, called REPRIEVE, showed that a class of cholesterol-busting drugs called statins can prevent a lot of cardiovascular disease events in people living with HIV whose cardiovascular disease (CVD) risk score meets a certain threshold. Spotlight previously reported on these findings, which showed that compared to placebo, daily treatment with 4mg oral pitavastatin – a specific statin – led to a 35% reduction in major adverse cardiovascular events (MACE) in people living with HIV classified to be at risk of cardiovascular disease.
When the findings were presented at the IAS conference, the study’s principal investigator, Dr Steven Grinspoon, said that while the researchers still have to assess more of the data collected to get a clearer picture of things, like the mechanisms driving cardiovascular disease across regions and conduct additional sub-group analyses, the study has already shown that using pitavastatin can save lives.
These sub-group analyses were discussed in greater detail at the Conference on Retroviruses and Opportunistic Infections (CROI) held in Denver in March this year. For the most part, the use of pitavastatin in the manner prescribed by REPRIEVE was considered a huge success, and the United States has since changed its guidelines to include the use of statins in the primary prevention of atherosclerotic cardiovascular disease.
Why it is different in South Africa
However, for low-and-middle-income countries like South Africa, the case for pitavastatin might not be as clear-cut. In fact, a panel discussion at CROI was dedicated to exploring the implications of the REPRIEVE findings for such countries.
Ntsekhe, who was a speaker on the CROI panel, tells Spotlight that data from REPRIEVE’s sub-group analyses reveal there was a striking difference in event rates – which in the case of the study are MACE in those who were getting the placebo – by country income status. He explains that as predicted in high-income countries, the event rates were high, while in low-and-middle income countries – particularly in Sub-Saharan Africa – event rates were very low.
He says one of the reasons for the difference in event rates was that the screening tool used in REPRIEVE worked well to identify those people living with HIV who might benefit from pitavastatin in high-income countries like the United States, but it did not work well in Sub-Saharan Africa.
This means using pitavastatin as part of a primary prevention strategy is a much more effective intervention in high-income countries than in low-and-middle income countries like in Sub-Saharan Africa because the cardiovascular disease profile is so different.
Ntsekhe explains the term cardiovascular disease itself is broad and all-encompassing and there are many forms, including valve disease, heart muscle disease, and vascular disease. The dominant form of cardiovascular disease in the high-income countries (which he refers to as the Global North) is known as atherosclerotic cardiovascular disease, which is characterised by a build-up of fatty deposits and plaque in the arteries.
In Sub-Saharan Africa though, Ntsekhe says “atherosclerotic cardiovascular disease is but one of many forms of cardiovascular disease”, taking the fourth or fifth place in the ranking of types of major heart disease.
Research conducted in high-income countries don’t always take differences in disease burden into account, according to Ntsekhe. This means that interventions researched in high-income countries and shown to be effective in that context won’t necessarily work as well in low-and-middle income countries like South Africa.
Strijdom concurs that while results from REPRIEVE in the global context were a game-changer, the findings are not easily transferable to South Africa’s context because pitavastatin is mainly aimed at reducing “bad cholesterol” and coronary artery disease (also called atherosclerosis).
‘Taking money away’
During the panel discussion at CROI, Ntsekhe asked whether Sub-Saharan Africa could justify taking money away from other health programmes that work in order to invest in pitavastatin.
“I said basically what should be a priority for us is a) finding tools that can better identify those at risk and b) continuing to focus on what our local data suggests are the priority areas,” Ntsekhe says.
“If your entire prevention strategy is aimed at atherosclerotic cardiovascular disease, but it isn’t the dominant cause of disease [in your country], you’re going to be treating a whole host of people to try and tackle this thing that affects very few in a sense,” he says.
“It was not anything about REPRIEVE, it was a wonderful study, the hypothesis was tested, and it was shown to be correct, the intervention we know works,” Ntsekhe says. “It really then comes down to regional areas to think very carefully about how best they’re going to get their biggest bang for their buck,” he says. “We have to carefully consider the local context, local burden, we have set local health priorities, and weigh benefit and cost before we adopt new interventions or recommendations.”
SA’s cardiovascular disease burden
While Strijdom says we don’t have great data, he points to a large systematic review and meta-analysis published in 2018 in Circulation, which estimates that around 15% of the total cardiovascular disease burden in South Africa is attributable to HIV. “It’s probably higher than that. I would say that probably about one in five people with heart disease have heart disease because of HIV in South Africa,” he says, adding “that figure is probably only going to increase”.
Because of this, he says, there is a need for proper and clear primary healthcare guidelines specifically aimed at managing cardiovascular disease in people living with HIV, which we don’t currently have.
Strijdom says what we have at the moment since the rollout of the 2019 National ART Clinical Guidelines is very basic guidelines. This involves screening someone who has just been diagnosed with HIV by taking their blood pressure, and testing urine for glucose and proteins, and an assessment of their general cardiovascular disease risk by taking their medical and family history. These guidelines, according to Strijdom, only make provision for routine screening at baseline, but screening guidelines at follow-up visits are insufficient.
“I am, however, aware of the fact that there is progress especially from the integrated chronic disease management model which is currently being piloted in South Africa – and hopefully with that will come much more definitive and universal guidelines,” he says. “The bottom line is that South Africa, in its public health [sector] especially, really very quickly needs to come up with very clear and more comprehensive guidelines to actively manage cardiovascular disease risk in people with HIV.”
Need for annual screening
Strijdom suggest that to improve screening for cardiovascular disease risk in people living with HIV, there needs to be annual screening of people’s weight, their measure of body fat based on height and weight, waist circumference, blood pressure, cholesterol and triglyceride levels as well as testing urine samples for kidney function. There also needs to be a thorough family and medical history conducted for each patient.
“It’s not really a very expensive or very exhaustive list of stuff that you have to do. Unless of course they have specific symptoms and signs that leads you in a specific direction that you then have to perhaps do an ECG [a test used to evaluate the functioning of the heart] or cardiac imaging but that is usually determined by what you get from their history and clinical examination,” he says.
Ntsekhe says public health strategies to combat the growing burden of non-communicable diseases (NCDs), including cardiovascular disease, in South Africa must be strengthened. These include screening and prevention tools like checking a patient’s blood pressure and blood glucose, advising against smoking and alcohol as well as promoting health lifestyle choices like exercise and weight loss. These interventions should be offered to everyone, regardless of whether they are living with HIV or not, he says.
“The thing about NCDs and cardiovascular disease, for the most part, they are diseases of lifestyle and behaviour. So, when you talk prevention, it’s not always about drug prevention,” he says. “It’s more about intensification of those [interventions] that are already in the public domain, are very effective, and cost very little. Many of the public health and primary healthcare guidelines do advise local ministries, local health authorities on what should be happening.”
In terms of public education, Stritjdom says people need to be aware that there is something like high blood pressure. “If people are aware they will come to the clinic and will say please measure my blood pressure,” he says.
“Our health system is understandably focused on infectious diseases, but if we are not careful, we will then be totally unprepared to tackle the epidemic that will have replaced it. Namely, cancer, heart disease, stroke, obesity, diabetes, and it will totally overwhelm our public healthcare system,” he says.
Colourised scanning electron micrograph of HIV (yellow) infecting a human T9 cell (blue). Credit: NIH
Australian researchers have discovered a previously unknown rogue immune cell that can cause poor antibody responses in chronic viral infections. The finding, published in the journal, Immunity, may lead to earlier intervention and possibly prevention of some types of viral infections such as HIV or hepatitis.
One of the remaining mysteries of the human immune system is why ‘memory’ B cells often only have a weak capacity to protect us from persistent infections.
In an answer to this, researchers from the Monash University Biomedicine Discovery Institute have now discovered that chronic viral infection induces a previously unknown immune B memory cell that does not produce high levels of antibodies.
Importantly the research team, led by Professor Kim Good-Jacobson and Dr Lucy Cooper, also determined the most effective time during the immune response for therapeutics such as anti-viral and anti-cancer drugs to better boost immune memory cell development.
“What we discovered was a previously unknown cell that is produced by chronic viral infection. We also determined that early intervention with therapeutics was the most effective to stop this type of memory cell being formed, whereas late intervention could not,” Professor Good-Jacobson said.
According to Dr Cooper, chronic viral infections have been known to alter our ability to form effective long-term protective antibody responses, but how that happens is unknown.
“In the future, this research may result in new therapeutic targets, with the aim to reduce the devastating effect of chronic infectious diseases on global health, specifically those that are not currently preventable by vaccines,” she said.
“Revealing this new immune memory cell type, and what genes it expresses, allows us to determine how we can target it therapeutically and whether that will lead to better antibody responses.”
The research team are also looking to see whether this population is a feature of long COVID, which results in some people having a reduced capacity to fight off the symptoms of COVID infection long after the virus has dissipated.
