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.
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.
Colourised scanning electron micrograph of HIV (yellow) infecting a human T9 cell (blue). Credit: NIH
Some people with HIV, known as “post-treatment controllers,” have been able to discontinue their antiretroviral treatment while maintaining an undetectable viral load for several years. Starting treatment early could promote long-term control of the virus if treatment is discontinued.
Scientists from the Institut Pasteur and other institutes used an animal model to identify a window of opportunity for the introduction of treatment that promotes remission of HIV infection. The findings, published in Nature Communications, suggest that starting treatment four weeks after infection promotes long-term control of the virus following the interruption of treatment after two years of antiretroviral therapy.
These results highlight how important it is for people with HIV to be diagnosed and begin treatment as early as possible.
Research on the VISCONTI cohort, composed of 30 post-treatment controllers, has provided proof of concept of possible long-term remission for people living with HIV. These individuals received early treatment that was maintained for several years.
When they subsequently interrupted their antiretroviral treatment, they were capable of controlling viraemia for a period lasting more than 20 years in some cases. At the time (in 2013), the team leading the VISCONTI study suggested that starting treatment early could promote control of the virus, but this remained to be proven.
In this new study, the scientists used a primate model of SIV1 infection which allowed them to control all the parameters (sex, age, genetics, viral strain, etc.) that may have an impact on the development of immune responses and progression to disease.
They compared groups that had received two years of treatment, starting either shortly after infection (in the acute phase) or several months after infection (in the chronic phase), or no treatment.
The reproducible results show that starting treatment within four weeks of infection (as was the case for most of the participants in the VISCONTI study) strongly promotes viral control after discontinuation of treatment.
This protective effect is lost if treatment is started just five months later.
“We show the link between early treatment and control of infection after treatment interruption, and our study indicates that there is a window of opportunity to promote remission of HIV infection,” comments Asier Sáez-Cirión, Head of the Institut Pasteur’s Viral Reservoirs and Immune Control Unit and co-last author of the study.
The scientists also demonstrated that early treatment promotes the development of an effective immune response against the virus.
Although the antiviral CD8+ T immune cells developed in the first weeks after infection have very limited antiviral potential, the early introduction of long-term treatment promotes the development of memory CD8+ T cells, which have a stronger antiviral potential and are therefore capable of effectively controlling the viral rebound that occurs after treatment interruption.
“We observed that early treatment maintained for two years optimises the development of immune cells. They acquire an effective memory against the virus and can eliminate it naturally when viral rebound occurs after discontinuation of treatment,” explains Asier Sáez-Cirión.
These results confirm how important it is for people with HIV to be diagnosed and begin treatment as early as possible.
“Starting treatment six months after infection, a delay that our study shows results in a loss of effectiveness, is already considered as a very short time frame compared with current clinical practice, with many people with HIV starting treatment years after infection because they are diagnosed too late,” notes Roger Le Grand, Director of IDMIT (Infectious Disease Models for Innovative Therapies) and co-last author of the study.
“Early treatment has a twofold effect: individually, as early treatment prevents diversification of the virus in the body and preserves and optimises immune responses against the virus; and collectively, as it prevents the possibility of the virus spreading to other people,” adds Asier Sáez-Cirión.
Finally, these results should guide the development of novel immunotherapies targeting the immune cells involved in the remission of HIV infection.
These are the initial results of the p-VISCONTI study, which began in 2015 in collaboration with the institutions cited above and received funding from MSD Avenir and the support of ANRS Emerging Infectious Diseases as part of the RHIVIERA consortium.
1 SIV: simian immunodeficiency virus only affects non-human primates. SIV infection of animals recapitulates the key features of human HIV infection.
Dr Vuyiseka Dubula-Majola, the former General Secretary of the Treatment Action Campaign, reflects on her journey and new role at the Global Fund. PHOTO: Joyrene Kramer
By Biénne Huisman for Spotlight
Dressed in a dark jacket, rain is pelting Vuyiseka Dubula-Majola’s face as she rushes past bare trees in Geneva, Switzerland. Along with her two children, Dubula-Majola has newly moved into a house in nearby Genthod, from where she commutes to work by train.
In October, the Global Fund to Fight AIDS, Tuberculosis [TB] and Malaria, appointed Dubula-Majola as head of their community, rights and gender department. The Global Fund has allocated tens of billions of dollars around the world to fight HIV since its inception in 2002.
Five weeks into the job, Dubula-Majola tells Spotlight that a big challenge for her will be to hone a new tool – that of diplomacy.
Laughing, the former General Secretary of the Treatment Action Campaign (TAC) says that in the past, diplomacy has not been her greatest strength.
“In this new job, I am required to be diplomatic,” she says. “Basically, diplomacy is being nice in the face of atrocities, and I am not that person. So it will be a huge challenge for me, it’s going to take a shift. I will have to keep asking myself, ‘what value I can add in this position?’ While developing new tools and new ways of fighting, without being the noisy person in the room.”
The power of collective action
Known for not mincing her words, the activist-scholar is talking to Spotlight over Zoom while walking to the Global Fund’s offices in central Geneva. She adds: “Activists don’t like bureaucracies by nature, but you have a voice here. You have political currency to shift things. It’s a tough one, but I’m there.”
In a 2014 TedX talk hosted in London, an inflamed Dubula-Majola told the audience that she is angry – angry with her father, angry with her government, angry at everyone. But that she was using her anger to fuel her work.
Vuyiseka Dubula-Majola was recently appointed at head of the Global Fund’s community, rights and gender department. PHOTO: Supplied
While she is in Switzerland, Dubula-Majola’s heart still brims with African proverbs, such as: “When spider webs unite, they can tie up a lion.” She has experienced the power of such collective action first-hand at the TAC, but now she’ll be applying it on a different stage. Indeed, her new job is “to ensure that the Global Fund strongly engages civil society and promotes human rights and gender equality”, with a particular focus on supporting community led organisations.
As a role model for her new diplomatic duties, Dubula-Majola cites American public health official Loyce Pace. “Loyce Pace who runs the health program in the United States government, she is very effective in what she does while hardly saying anything in public. But she is shifting norms – bringing priority to black and poor people. She uses her allies and many other people similar to her to say things louder than she could…I guess this is another step of growth in my activist journey – to still be as effective, as radical, the very same eagerness and passion, but silently.”
‘There was no time to dream’
Dubla-Majola grew up in a village near Dutywa in the Eastern Cape. Aged 22 in Cape Town in 2001, she spiralled with depression after being diagnosed with HIV. But instead of resigning herself to what was then still a death sentence for most people, she joined the TAC – working night shifts at the McDonalds drive-through in Green Point, while by day she joined the fight to bring antiretrovirals and other medicines to South Africa.
“As a 22-year-old, I did not have fun, there was no time to dream,” she recalls. “I was fighting for my life and the lives of others. I never thought I would have children, I never thought I would get married, I never thought I would love again. Because there was also the issue of who infected me, how did this happen? You start resenting relationships.”
At the forefront of social justice activism for most of South Africa’s young democracy – a role model for people living with HIV, and for those fighting inequality – Dubula-Majola lead the TAC from 2007 to 2013, after which she joined Sonke Gender Justice as director of policy and accountability. She holds an MA in HIV/AIDS management from Stellenbosch University; her PhD from the University of KwaZulu-Natal examined “grassroots policy participation after a movement has succeeded to push for policy change,” using MSF’s [Médecins Sans Frontières] pioneering antiretroviral sites in Khayelitsha and Lusikisiki as samples.
‘Build and regain the dignity of poor people’
In 2018, when Stellenbosch University offered her a job as director of its Africa Centre for HIV/AIDS Management, Dubula-Majola was circumspect. Why take up appointment at a white male-dominated institution shackled by slow transformation, in an elitist town? But she took on the challenge to become the transformation she wanted to see.
Dubula-Majola tells Spotlight that while relishing the privilege of academia – a space to reflect – it saw her away from “the heat of the activist fire” for too long. Five years later, a new challenge awaits.
Reflecting on Stellenbosch, she says: “This [job at the Global Fund] is even harder, because it’s not just one country, one university. This is all the continents of the world. All of them facing the same thing, the struggle here is to build and regain the dignity of poor people around the globe.”
Despite her early misgivings about relationships, Dubula-Majola married fellow TAC activist, Mandla Majola. Their children, now aged 10 and 16, are HIV-negative. Presently Majola is helping with their friend Zackie Achmat’s independent campaign for the 2024 general elections, after which he will join his wife in Geneva. The family will unite in Switzerland for Christmas though – “which will be the most miserable and cold Christmas,” says Dubula-Majola, laughing. “It will be our first winter Christmas and our last. As we just arrived a month ago, it doesn’t make sense to travel back to South Africa for the holidays.”
Overall she says she remains hopeful, adding that movements like #MeTo are lessons in global solidarity.
Her thoughts on continuing the fight against HIV: “It is up to HIV positive people, and those who want to remain HIV negative, to steer towards an AIDS-free generation. We must stop complaining, thinking politicians will do everything for us, and do it ourselves.”
Meanwhile, Global Fund representatives have voiced confidence in Dubula-Majola’s ability to lead. Marijke Wijnroks, head of the organisation’s strategic investment and impact division, said in a statement: “Following an extensive search process, I am delighted to say that we found the ideal person for this role. As a person living with HIV, Vuyiseka’s lived experience and leadership style are well aligned to what we need from this critical role.”
Note: Dubula-Majola is a former General Secretary of the TAC. Spotlight is published by SECTION27 and the TAC, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
An unexpectedly high percentage of children, who were born with HIV and started treatment within 48 hours of life, exhibit biomarkers by two years of age that may make them eligible to test for medication-free remission, according to a multinational study published in The Lancet HIV.
“Moving away from reliance on daily antiretroviral therapy (ART) to control HIV would be a huge improvement to the quality of life of these children,” said Protocol Co-Chair and senior author Ellen Chadwick, MD, at Ann & Robert H. Lurie Children’s Hospital.
Conducted in 11 countries including South Africa, the proof-of-concept study was charged with replicating the case of HIV remission as seen in the “Mississippi baby” that was reported in 2013. In that case, the infant started ART at 30 hours of life, was treated for 18 months, and achieved 27 months of ART-free remission before the virus rebounded. Typically, if ART is stopped, the virus rebounds within a month.
The study included a three-drug ART regimen initiated within 48 hours of life, with the fourth drug added within 2-4 weeks. This is very early treatment compared to the standard of care where three-drug ART may not begin until 2-3 months of age.
In the US, however, based on earlier findings from this study, very early treatment is now the norm for infants at high risk of acquiring HIV infection from their mother.
“With earlier treatment, we hope to limit or prevent the establishment of viral reservoirs in the body. These viral reservoirs hold small amounts of hidden virus which are hard to reach with ART. By shrinking these reservoirs, we expect to increase the amount of time that patients can be in remission, without needing daily ART,” said co-author and Protocol Co-Chair Jennifer Jao, MD, MPH, from Lurie Children’s.
Dr Chadwick adds: “Another benefit of smaller viral reservoirs might be that newer treatments such as long-acting antibody therapies or therapeutic vaccines could potentially be used instead of daily ART.”
“Our results show a higher percentage of children might be eligible to interrupt therapy than we expected, and the next step is to stop ART and see how many children actually achieve remission,” said Dr Chadwick.
“If even one child achieves remission, that would be considered a success. Today, newer more effective and better tolerated HIV medications are available for infants than when the study began, strengthening the prospect of limiting viral reservoirs and testing for possible remission in infants and children with HIV. Overall, this is an exciting advancement and an opportunity to change the course of pediatric HIV infection.”
The study was conducted in 11 countries – Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand, Uganda, USA, Zambia and Zimbabwe.
A new injectable solution that self-assembles into a gel under the right conditions could help manage HIV unlike any currently available methods, researchers report in the Journal of the American Chemical Society. Developed by John Hopkins University researchers, the new gel releases a steady dose of the antiretroviral lamivudine over six weeks, suggesting people living with HIV could have an alternative to the daily pill regimen.
“The primary challenge in HIV treatment is the need for lifelong management of the virus, and one way to address this is to reduce dosing frequencies to help patients stick to medical regimens,” said lead researcher Honggang Cui, a chemical and biomolecular engineer. “This new molecular design shows us a future in which drug hydrogelation can do that to improve HIV treatment.”
In plasma-like conditions, Cui’s team showed the gel quickly separates into molecules of lamivudine. By injecting the gel in the backs of mice, the researchers found one injection was sufficient to maintain effective and lasting drug concentrations for 42 days with nearly no side effects.
“Our goal is to help improve people’s quality of life,” Cui said. “The antiviral substance can be injected under the skin and remain in place over an extended period, releasing the therapeutic compound slowly and consistently – a critical need for individuals with HIV.”
For people living with HIV, the key is maintaining bloodstream drug levels at concentrations that suppress virus load in the body. But that can be difficult with traditional approaches because the body naturally rids itself of these chemicals, Cui said, which is why different treatments require different dosages and dosing frequencies to work.
Most antiretroviral therapies use a combination of drugs, so the researchers plan to include other drugs in tests. Because lamivudine is an FDA-approved drug to treat HIV and hepatitis B, the researchers said the hydrogel could also help manage hepatitis B.
“This is a novel way to deliver anti-HIV meds, and this platform has the advantage that a single polymer can be programmed to deliver several different drugs simultaneously,” said co-author Charles W. Flexner, a professor of medicine, pharmacology, and molecular sciences in the Johns Hopkins School of Medicine. “One of the drawbacks of the approved injectable HIV treatments is that none have activity against hepatitis B virus, which is a common co-infection with HIV, especially in Asia and Africa. This formulation delivers lamivudine, a drug active against both HIV and HBV, but can also be modified to deliver tenofovir, which is the current standard of care for HBV treatment.”
The team envisions their hydrogel working as a preventive measure, similar to how some people take anti-HIV drugs to avoid infection.
“Keeping the high drug levels in plasma for 42 days is very impressive,” Cui said. “But in the future, we hope it will be even longer.”
Hydrogels have unique water-absorbing properties that give them a jellylike consistency resembling biological tissue. The new gel undergoes self-formulation, stays close to the site of injection, and separates into molecules that can fend off the virus without the need for additional carriers or delivery materials.
“The most exciting aspect of these gel filaments is that they consist entirely of the therapeutic agent itself,” Cui said. “Everything originates from the same compound after injection, and this simplest drug formulation could streamline the regulatory approval process once clinical efficacy is demonstrated.”
The team tweaked the molecular properties of lamivudine to act as the building blocks of a supramolecular polymer, a large chain of repeating molecules that can either stick together tightly or come apart, depending on temperature, pH, and other external conditions.
Specially trained and accredited pharmacists in South Africa will now be allowed to provide people with medicines to prevent HIV and tuberculosis (TB) and to treat uncomplicated HIV without a doctor’s script. This is because the North Gauteng High Court this week ruled against an application by the IPA Foundation (an association of private doctors) attempting to block the implementation of Pharmacist-Initiated Management of Antiretroviral Therapy (PIMART).
PIMART involves the introduction of a legislative framework, a specialised training course, and an accreditation process to allow pharmacists to supply HIV and TB medicines to people visiting pharmacies, under certain conditions, without a doctor’s script.
While PIMART has been delayed for two years by the IPA Foundation’s legal challenge, Judge van der Schyff’s ruling now clears the way for the SAPC to proceed with its implementation.
Steve Letsike, Chair of the SAPC’s Health Committee and PIMART Task Team, said in a media conference on Thursday that the IPA Foundation has until 8 September to appeal the High Court’s decision. Speaking at the same media conference, Mogologolo Phasha, President of the SAPC, indicated that if the IPA Foundation appeals the ruling, the SAPC will continue to fight to preserve the initiative in higher courts.
Spotlight asked the IPA Foundation whether they plan to appeal the decision, but no response was received by time of publication.
The background
The introduction of PIMART was proposed by the SAPC in 2018 in response to a request from the National Department of Health for the SAPC to develop an intervention to enable pharmacists to help get HIV prevention treatment to more people quicker.
Pharmacists trained and accredited under the PIMART initiative will be able to provide preventative therapy for HIV (both post-exposure and pre-exposure prophylaxis – PEP and PrEP), TB preventive therapy, and first-line antiretroviral treatment for uncomplicated HIV.
According to Phasha, around 900 pharmacists, or 5% of pharmacists on the register have already undertaken specialised, supplementary training to enable them to provide PIMART services. He noted, however, that before trained pharmacists would be able to start providing PIMART services they would need to receive accreditation in the form of a permit granted by the National Department of Health under Section 22(A)15 of the Medicines and Related Substances Act.
The court’s response to the IPA Foundation’s arguments
In February 2022, the IPA Foundation filed an affidavit with the North Gauteng High Court seeking review and dismissal of the SAPC’s decision to implement PIMART and related legislation.
In its affidavit, the IPA Foundation argued that the provision of PIMART services falls within the domain of medical doctors and that pharmacists do not have the required training and competencies to provide these services. The IPA Foundation further argued that the SAPC does not have the legislative mandate to introduce PIMART, that the SAPC’s reasons for implementing PIMART were not adequately explained, and that the SAPC’s procedures for implementing PIMART were not procedurally fair and did not provide adequate opportunity for interested parties to comment.
The IPA Foundation warned of a “slippery slope” resulting from PIMART’s introduction, adding “this objection essentially warns of the opening of the floodgates or perhaps an anticipated negative precedent setting occurrence relevant to the provision of medication… without prescription”.
In her ruling, Judge van der Schyff noted that while tension between healthcare cadres regarding their scopes of practice is common, the World Health Organization calls for “a collaborative approach to primary healthcare issues and the embracing of task-shifting”.
She added that “competition, per se, does not limit or curtail the rights of medical practitioners to continue providing the services that they currently provide,” further stating that “even if the assumed competition is regarded to affect family practitioner’s rights adversely, the alleged adverse effect it holds for medical practitioners has to be considered against the need to expand primary healthcare services aimed at preventing and treating HIV”.
Judge van der Schyff dismissed the IPA Foundation’s argument that the SAPC is not mandated to introduce PIMART, stating that “the SAPC is empowered to prescribe the scope of practice of the various categories of persons registered in terms of the Pharmacy Act”. She added, “The development and implementation of PIMART, does not expand the existing scope of practice of pharmacists that generically provides for PIT [pharmacist-initiated therapy] and PCDT [primary care drug therapy]. It introduced a specialised category of PIT and PCDT focused on preventing and treating HIV.”
Judge van der Schyff also rejected the IPA Foundation’s arguments that PIMART’s introduction was procedurally unfair and the decision for its implementation was not properly explained, arbitrary, or capricious. She says that “through its collaboration with the Southern African HIV Clinicians Society, whose members include numerous medical doctors, the development of PIMART was given great exposure”.
“The need to widen access to first-line ART [antiretroviral therapy] and TPT [TB preventative therapy] on a community level is not a figment of SAPC’s imagination, but a dire need that is also evinced in other countries,” held van der Schyff.
Finally, Judge van der Schyff rejected the argument that pharmacists are not adequately trained to provide PIMART services, stating, “The PIMART training course was developed to ensure that pharmacists who successfully completed the training would be ‘suitably qualified to safely and effectively assist in providing ART’.” She adds that the PIMART training course was “developed by suitably qualified experts in the field, which experts include medical practitioners”.
The ruling was welcomed by the SAPC and several HIV groups.
“The superior court yesterday (Wednesday) confirmed what has been our long-held view that PIMART is a necessary and competently designed intervention programme to support South Africa’s efforts in providing access to patients diagnosed with HIV and AIDS,” said Phasha. “The programme may also arrest and lower the ballooning HIV budget, which is nearly half the national health budget, by reducing the rate of new infections.”
Nelson Dlamini, Head of Communications at the South African National AIDS Council (SANAC), told Spotlight that SANAC welcomes the court ruling.
“The magnitude of South Africa’s HIV burden requires innovative ways of accessing HIV treatment, care, and support. PIMART is one such approach that will improve access to antiretroviral therapy for people living with HIV and those requiring PEP & PrEP,” said Dlamini.
Sibongile Tshabalala, Chairperson of the Treatment Action Campaign (TAC), said the organisation also welcomes the ruling. “The challenges that we are facing in the country include one of people queuing for a long time in facilities… and also the attitude of nurses in facilities which chases away so many people from facilities. We also have the issue of key populations that are not comfortable to go in public health facilities to access medication… so if a pharmacist is able to issue and prescribe ARVs and TB medication it will mean that we will be able to cover a lot of people.”
*NOTE:A representative of the TAC is quoted in this article. Spotlight is published by SECTION27 and the TAC, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
Photo by Miguel Á. Padriñán: https://www.pexels.com/photo/syringe-and-pills-on-blue-background-3936368/
The South African Pharmacy Council (SAPC) has been given judicial go-ahead to introduce its Pharmacy-Initiated Management of Antiretroviral Treatment (PIMART) initiative, which will allow specially trained pharmacists to manage and prescribe medicine to patients with HIV and tuberculosis.
Pretoria High Court Judge Elmarie van der Schyff has dismissed an application brought by a doctors’ organisation – the IPA Foundation – for the setting aside of the programme.
She said the pilot project had emphasised the value of the initiative, which was in line with the World Health Organisation’s vision to promote widely accessible primary health care.
“The untapped value of pharmacists in fighting HIV was also emphasised by the efficient role pharmacies played in meeting health care needs and providing health care services during the Covid-19 pandemic,” she said.
“The need to widen access to first line ART and TPT therapy on a community level is not a figment of SAPC’s imagination but a dire need that is also evinced in other countries.”
The IPA Foundation approached the court, under the Promotion of Administrative Justice Act (PAJA), seeking to review and set aside the SAPC’s decision to implement PIMART.
IPA claimed that the SAPC had failed to give interested parties an adequate opportunity to comment before the initiative was implemented. It further contended that PIMART unjustifiably encroached on the domain of medical practitioners and was in conflict with legislation.
IPA also accused SAPC of misleading the Director-General of Health, claiming there had been extensive consultation with stakeholders, which led to the approval and issuing of permits for the initiative.
The SAPC said the application should be dismissed. It said pharmacy-provided primary healthcare was a well known and functional concept in South Africa and PIMART was simply a “widening of this”.
Referring to the background and context, Judge van der Schyff said, in line with WHO recommendations that all people living with HIV must be provided with ART, the department of health had requested the SAPC to consider and implement interventions that would ensure that patients had increased access to medicines.
This led to the SAPC requesting the Director-General in August 2018 to consider issuing permits to pharmacists who had completed supplementary training, to manage patients and to dispense medication under PIMART.
In March 2021, the SAPC published a notice for public comment regarding the adoption of PIMART. The first permits were issued in August that year.
However, IPA submitted objections outside of the timeline for comments. It said this was because its members were struggling with another wave of the Covid-19 pandemic.
“Pharmacists and doctors operate in distinct and separate professional domains, the boundaries of which are closely guarded and some tension exists … IPA’s objection to PIMART seems to be rooted, partially at least, in this professional tension.
“This is evidenced by its fear that the decision to implement PIMART might ‘open the floodgates’ and ‘pave the way for pharmacists to ultimately treat and prescribe other schedule 4 drugs in respect of acute illnesses’,” the Judge said.
She noted, however, that the National Drugs Policy, in line with WHO guidelines, promoted “task shifting” to advance access to medicine and that at primary level, prescribing should be competency based, not occupation based.
Any alleged adverse effect that PIMART held for a medical practitioner had to be considered against the need to expand primary health care services aimed at preventing and treating HIV and providing first-line ART therapy.
Judge van der Schyff said the initiative gave members of the public a choice as to whether they wanted to approach a pharmacist, who had been issued with a permit, or a general practitioner.
In considering procedural fairness, the judge said there was nothing sinister in the timing of the notice calling for comment, that the project was not something hidden in secrecy and “I find it improbable, as alleged, that none of IPA’s members had timeous knowledge of the board notice”.
The decision to implement PIMART also fell within the ambit of the SAPC’s powers.
Evidence also showed that the PIMART training course was developed to ensure that pharmacists who successfully completed the training would be suitably qualified to safely and effectively assist in providing ART.
Judge van der Schyff dismissed the review application and ordered IPA to pay the costs.
Professor Francois Venter, former President of the Southern African HIV Clinicians Society and Director of Ezintsha, an HIV research organisation at Wits University, commented, “I hope this is the end of it. The pharmacies are an essential part of the health system, and pharmacists internationally play a big role in expanding HIV services.”
In what is likely one of the largest treatment rollouts in South African history, well over four million people living with HIV have started taking the antiretroviral dolutegravir since its introduction around four years ago. Now, according to a recent study published in the Lancet medical journal, use of dolutegravir in South Africa is associated with more people staying on treatment and higher rates of viral suppression.
The use of a three-in-one combination of the antiretroviral drugs tenofovir, lamivudine and dolutegravir (TLD for short) for the treatment of HIV was first recommended by the World Health Organization (WHO) in 2018. A year later it was recommended in the South African treatment guidelines as first line treatment for HIV and a three-year tender was awarded. Since then, dolutegravir has largely replaced another antiretroviral called efavirenz.
Today, TLD is the recommended treatment option for most people living with HIV in the country. The 2023 National antiretroviral (ARV) guidelines also include recommendations for the use of child-friendly formulations of dolutegravir and dolutegravir containing regimens in kids. Spotlight reported on these here.
Around 4.7m people in SA taking dolutegravir
According to Foster Mohale, spokesperson for the National Department of Health, in 2019 the HIV clinical guidelines were revised to include a fixed combination dose of TLD “for all eligible people for use as the first line regimen.”
Based on this, the department set a goal that 90% of those eligible for it should receive TLD as a first line regimen. In terms of meeting this goal, Mohale says that by March 2023, just over four million (4 127 427) people were on TLD. Additionally, about 650 000 (653 884) people were on other dolutegravir based regimens. Altogether, there are thus now over 4.7 million people in the country on treatment combinations that include dolutegravir.
“Based on the March 2023 data, 90% of clients on first line regimen were on TLD. However, performance varies by province,” he says.
Of the total number of people on ART in the public health sector, 75.8% are on TLD, according to Mohale.
Trends in the roll out
While on paper the country’s transition from efavirenz to dolutegravir-based regimens seems to have been smooth, the reality on the ground has been more complex. A study published in the Lancet earlier this year looked at real-world rollout data from 2019 to 2022. The study was conducted in 59 clinics across the country and collected data from two cohorts-one cohort were first time initiators of ART and the other were transitioning from regimens that did not include dolutegravir to ones that did.
In the initiator cohort, just over 45 000 people were initiated on ART between December 2019 and February 2022. Of those, 68.9% were initiated on dolutegravir-based regimens, 31.1% on efavirenz-based regimens, and 0.1% on nevirapine-based regimens.
Those initiated on dolutegravir-based regimens were more likely to still be on treatment a year later and were also more likely to be virally suppressed than those who were initiated on the other regimens.
In December 2019, in the transition cohort, just over 180 000 people were on a non-dolutegravir first line regimen. By February 2022, 67% of them had transitioned to a dolutegravir-based regimen. These people were also more likely to be retained in care at 12 months and be virologically suppressed than those who had not switched to a dolutegravir-based regimen.
“That’s good for a number of reasons. It means that the treatment’s working, people are less likely to get unwell and also, they can’t transmit the virus onto other people,” explains Dr Jienchi Dorward, one of the study authors and an academic clinical lecturer at the University of Oxford and honorary associate scientist at the Centre for the AIDS Programme of Research in South Africa (CAPRISA).
‘Bumpy transition’
Dr Yukteshwar Sookrajh, a Senior Medical Practitioner at the eThekwini Municipality Health Unit who was also involved in the study, tells Spotlight that the rollout quickly gathered momentum.
“But initially there were some issues to navigate around drug interactions; concurrent TB infection and the use of dolutegravir in women of childbearing potential,” he says. “Once those concerns were addressed, the comfort of switching to dolutegravir was increased and we find that the majority of our patients have now safely transitioned across to dolutegravir-based regimens.”
In many ways South Africa was slow in rolling out dolutegravir compared to other African countries, according to Professor Francois Venter, the head of Ezintsha at Wits University. Reasons for this, he says, include an initial concern around the safety of dolutegravir use among pregnant women, and disruption in training due to the COVID-19 pandemic.
He says that the South African Clinicians society was alerted during the COVID-19 pandemic that many patients in the public health sector had still not been transitioned to dolutegravir. An education campaign was then launched to encourage clinicians to start or switch patients to dolutegravir.
However, as it stands now the rollout of the drug in the public sector has been a huge success, despite what Venter calls a “bumpy transition”.
Initial safety concerns
One important reason to conduct the study reported in the Lancet, according to Dorward, was a safety concern regarding the use of dolutegravir by pregnant women. An earlier study conducted in Botswana called Tsepamo found a higher prevalence of neural-tube defects (a type of birth defect) associated with dolutegravir exposure at conception than with other types of antiretroviral exposure. As more data has been gathered since, it has however become clear that dolutegravir does not in fact increase the risk of neural-tube defects.
But the Tsepamo scare did impact who was initiated and transitioned onto dolutegravir in first two years of the rollout.
“The initial concerns around neural-tube defects and the use of dolutegravir in women of childbearing potential clearly hampered rollout of dolutegravir in women – and this has been clearly demonstrated in this study,” says Sookrajh.
The Lancet study found that pregnant women and non-pregnant women were less likely to be initiated on dolutegravir than men early in the rollout, with the biggest difference between women and men aged 15 to 24 years old. This difference decreased with age and by age 55 there was no difference between men and women receiving dolutegravir.
But this changed over time and by September 2021 women were as likely to get initiated on dolutegravir as men. Spotlight previously reported that the rollout was done in two stages. In the first stage men, adolescent boys, women on reliable contraception, and older women were prioritised.
Of those who started treatment during the study period, 46.9% of the pregnant women in the cohort were initiated on dolutegravir-based regimens, while 63.9% of the non-pregnant women and 82.3% of the men in the cohort were initiated on dolutegravir-based regimens.
“In both those groups [cohorts] we found that women were less likely than men to get dolutegravir, but interestingly, this was particularly in younger women,” Dorward explains. “As time went on, the difference between men and women became much less…around June to September 2021 was a time period where we found that women and men pretty much began to equally get dolutegravir.”
Dorward says the data showed an uptick in women in the study being given dolutegravir once the South African guidelines changed to reflect that there was no longer a concern around neural-tube defects. It is thus likely that the safety concern was responsible for the lower initial uptake among young women.
He adds that the messaging around this potential risk was based on the evidence available at the time and was clearly outlined in the guideline document and training for dolutegravir use, but these did not appear to adequately allay these concerns among healthcare workers.
“The risks versus benefits needed to be messaged in a more effective way such that healthcare workers were more comfortable and confident in offering dolutegravir to women,” he says. Based on this experience Sookrajh adds that in future there needs to be more engagement with “practitioners on the ground to determine what type of messaging and supportive materials are required to facilitate better understanding of guidelines at the coal face.”
Another concern for some healthcare workers has been that dolutegravir-based regimens have been associated with greater weight gain than efavirenz-based regimens. But, as argued in a recent editorial in the Southern African Journal of HIV medicine, association is not the same as causation and it may well be that efavirenz inhibits weight gain rather than dolutegravir promoting it. People living with HIV who start taking antiretroviral medicines often gain weight as their health recovers.
New guidelines should further boost uptake
Sookrajh says that the National Department of Health’s antiretroviral (ARV) 2023 guidelines will further improve the uptake of dolutegravir in the public healthcare system.
“With the April 2023 National Department of Health ARV Guidelines, we actually find that further barriers to switching to dolutegravir have been removed and dolutegravir is clearly placed as the preferred drug of choice in almost all scenarios for both first- and second-line antiretrovirals,” he says.
“I think the new [ARV] guidelines hopefully will be a big improvement for people who are on treatment, and part of that is possible because we’re using the drug that is better. You’re less likely to get resistance with dolutegravir so we’re less worried if people don’t take treatment properly that they might get drug resistance, although we still need more research to be sure about that,” Dorward says. “And it’s still very important for people to take treatment consistently to suppress the virus and maintain their own health and prevent onward transmission.”
According to Venter, there needs to be proper resistance surveillance to detect potential dolutegravir resistance.
“We can’t take for granted we’ll never have resistance [to dolutegravir]…eventually there will be the occasional patient that does have resistance, but we need proper surveillance there,” he says. “And then we need to keep an eye on things. There are still patients getting HIV…there’s still a lot of new infections…we need to make that stop…we’ve got amazing PrEP and way too few people getting it. So, we do need to start addressing that.” (PrEP, or pre-exposure prophylaxis, refers to antiretrovirals taken to prevent HIV infection.)
Venter adds that while successful in the public health sector, the uptake of dolutegravir has been extremely slow in the private health sector for reasons unknown to him.
