Minister of Health Dr Aaron Motsoaledi. Source: GCIS
By Anna Grimsrud and Sibongile Tshabalala-Madhlala
Minister of Health Dr Aaron Motsoaledi’s recent claim that over half a million people have been newly started on HIV treatment in less than six months has raised eyebrows in health circles. In this open letter, Anna Grimsrud and Sibongile Tshabalala-Madhlala, associated with CHANGE – South Africa, ask the Minister to explain numbers that, on the face of it, seem contradictory.
Dear Minister Motsoaledi,
We write to you in response to your 15 May 2025 press statement and subsequent remarks in Parliament on the current status of the national HIV, AIDS, and TB campaign.
You stated that since the launch of the Close the Gap campaign, 520 700 people have been initiated on HIV treatment, reaching “more than 50% of the target”. You also stated that 5.9 million people are currently on antiretroviral therapy (ART). However, at the campaign’s launch on 25 February 2025, you reported the same number on HIV treatment — 5.9 million. This raises a critical question: if over half a million people have started or restarted treatment, why has the total number of people on treatment not increased?
If both figures are accurate, this would mean that approximately 520 000 people have been lost from care over the past few months — a deeply concerning and unprecedented level of attrition. We respectfully request that you provide the underlying data and clarify the current total number of people remaining on HIV treatment.
There are several reasons why we are concerned:
Static treatment numbers: As noted, the number on treatment was reported as 5.9 million in both February and May 2025. If 520 700 people have been initiated or re-initiated during this period, the same number must have exited care — a scenario that requires urgent explanation.
Slow growth in the number of people on treatment: According to official statements, the total number of people on HIV treatment increased by only 100 000 between March and December 2023 — from over 5.7 million to 5.8 million. The claim that the cohort has now grown by over 500 000 in a matter of months contradicts recent trends.
Declining lab numbers: National Health Laboratory Service data reported by the Daily Maverick and Reuters, show notable declines in viral load testing and early infant diagnosis in March and April 2025 compared to the same months in 2024. These indicators should increase alongside meaningful growth in treatment uptake — not decrease.
In light of these concerns, we believe it is essential that you provide a transparent accounting of the current number of people on treatment and the metrics being used to assess progress under the Close the Gap campaign. Specifically, we request data demonstrating that the programme is on track to meet its stated goal: increasing the number of people on treatment from 5.9 million to 7 million.
We share your commitment to a strong and effective HIV response, especially in this period of financial and operational strain. Like you, we believe it is vital that accurate and complete information is shared with the public and Parliament at this critical moment.
*Anna Grimsrud is an epidemiologist with a PhD in Public Health and writes in her personal capacity. Sibongile Tshabalala-Madhlala is openly living with HIV and currently serves as the National Chairperson of the Treatment Action Campaign (TAC).” CHANGE is a coalition of more than 1 500 people from civil society organizations in South Africa and around the work — people living with HIV, activists, community health workers, researchers, programme members, epidemiologists, clinicians, economists, and others. CHANGE stands for Community Health & HIV Advocate Navigating Global Emergencies.
Note: Spotlight aims to deepen public understanding of important health issues by publishing a variety of views on its opinion pages. The views expressed in this article are not necessarily shared by the Spotlight editors.
Republished from Spotlight under a Creative Commons licence. Views expressed in the original article are not necessarily shared by Quicknews.
Image caption, left to right: Dr Lisa Mulenga, Country Director of Girl Effect and Gauteng MEC for Health, Ms. Nomantu Nkomo-Ralehoko, engaging with a student at VUT.
Johannesburg, 13 May25: Girl Effect South Africa, a non-profit organisation, joined the Department of Health, South African National Aids Council, Higher Health, and other partners at the ‘Close the Gap Higher Education’ event which took place on Friday, 9 May, at the Vaal University of Technology (VUT). The campaign aims to connect young people with essential health services, encourage HIV testing and treatment, and help close the country’s significant treatment gap.
With young people making up a large proportion of the estimated 5.7 million South Africans living with HIV but not on antiretroviral therapy (ART), the campaign focuses on improving access to youth-friendly healthcare on campuses and in communities. The VUT activation is part of a national strategy to achieve the UNAIDS 95-95-95 targets, which aims to ensure that 95% of people living with HIV know their status, 95% of those are on treatment, and 95% of those on treatment achieve viral suppression.
Girl Effect brings its experience in youth-centred communication, behaviour change, and media to help break down stigma and promote informed, confident decision-making among young people. Its focus is especially on adolescent girls and young women, who remain at higher risk of HIV infection and are often underserved by the health system.
Through its flagship programme, Jik’iZinto, Girl Effect connects young women with transformative health education and digital engagement, empowering them to make informed decisions about their health and wellbeing.
Over 1 687 students accessed HIV counselling, testing, ART initiation and contraceptive services at the event and 38 700 female and male condoms where distributed amongst the young people. The young people were educated on oral Pre-Exposure Prophylaxis (PrEP), a daily pill that significantly reduces the risk of contracting HIV. Young people were also encouraged to conduct screenings for STIs, TB, and chronic diseases. Additionally, students actively participated in youth dialogues and peer-to-peer health education.
“Too often, young people face barriers, whether social, structural or emotional, that prevent them from seeking the healthcare they need,” said Dr Lisa Mulenga, Country Director of Girl Effect South Africa. “At Girl Effect, we work to remove those barriers by creating platforms where young people can access accurate information, engage with relatable content, and feel supported in making decisions about their health.”
Dr Mulenga, a public health and health systems expert with over two decades of experience, leads Girl Effect’s national strategy and programme delivery. The organisation collaborates with government departments, civil society and local partners to strengthen health messaging and improve access to services for underserved groups.
Gauteng MEC for Health, Ms. Nomantu Nkomo-Ralehoko, engaged with stakeholders during the event, culminating in a pledge signing ceremony. This event demonstrated the health department’s commitment to collaborative efforts in addressing health challenges and promoting meaningful partnerships.
The ‘Close the Gap Higher Education ’ campaign aligns with the National Strategic Plan on HIV, TB and STIs (2023 – 2028), which calls for improved service integration, greater community outreach, and targeted youth interventions. In addition to healthcare services, the VUT activation featured student-led dialogues, physical wellness activities, live performances, and keynote addresses from key decision-makers.
The campaign is being delivered in partnership with Shout It Now, Soul City, LoveLife, Aids Healthcare Foundation, the South African Police Service (SAPS), and various youth organisations. The goal is not only to increase uptake of services but to change the way young people experience healthcare, making it accessible, welcoming, and relevant to their lives.
Sex workers in Vosloorus, Johannesburg and Springs talked to GroundUp about their struggle to access health services, particularly antiretroviral treatment, since the closures of US funded clinics. Photos: Kimberly Mutandiro
It’s afternoon on Boundary Road in Vosloorus. Sex worker Simangele (not her real name) hopes to secure her next client.
Making enough money to pay rent has always been a concern for Simangele. But now she has a new worry: how to keep up with her antiretroviral treatment.
Two months ago the closure of a mobile clinic — where Simangele and other sex workers in Vosloorus went for checkups and to collect their treatment — left her without access to the life-saving medication.
The mobile clinic was run by the Wits Reproductive Health and HIV Institute (WITS RHI) which heavily relied on US funding. The institute has been providing critical sexual and reproductive health services since 2018. The programme was one of many health facilities forced to halt services at the end of January in the wake of US funding cuts for global aid.
Speaking to GroundUp, Simangele says she ran out of antiretroviral medicines (ARVs) over a month ago and has resorted to borrowing a few tablets from a friend. “I don’t know what I will do because the tablets my friend gets give me side effects,” she says. (Antiretrovirals treat HIV. They have to be taken daily for life.)
She says the clinic closed without any warning or before they could give them transfer letters to public healthcare facilities. She is now dreading having to go to a public facility where she says sex workers are frequently discriminated against, particularly those who are undocumented.
We spoke to a dozen other sex workers in Joburg and in Springs who are worried about defaulting on their antiretroviral treatment following the closure of the Wits RHI clinics. The clinics also provided pre-exposure prophylaxis (PrEP) (to prevent HIV-negative people contracting HIV), and treatments for sexually transmitted infections, TB, sexual reproductive health services, and counselling.
A sex worker shows the last few ARVs she has left.
Another sex worker said, “The minute we go to public clinics, they will need documents, which some of us do not have … Wits made time to listen to our problems as sex workers. Even when we faced challenges with clients, they never judged us.”
Sisi (not her real name), who rents rooms and assists sex workers in Vosloorus, said she’s aware of several sex workers who have defaulted and no longer have access to condoms, lubricants, and treatment for sexually transmitted infections. “The Wits clinic did not discriminate against people without documents and would sometimes provide food, branded T-shirts, caps, and even jobs,” she said.
“Many of us will die”
We visited Zig Zag Road in Springs, where several sex workers said they were out or almost out of ARVs. When asked why they didn’t just go to a local clinic, they told GroundUp about instances where they experienced stigma while trying to access treatment at public clinics.
“I used to receive PrEP to help prevent HIV (from the Wits clinic). We would also receive birth control services. Now I can’t go to a public clinic because we are mocked for being sex workers,” said Siphesihle.
Ntombi, who waits for clients along End Street, attended one of the Wits clinics in Hillbrow which closed down. She said those on PrEP were given transfer letters before the clinic closed.
Other workers nearby told GroundUp that they now pay up to R250 for PrEP, which is more than they can afford.
Sisonke calls for urgent response to crisis
The Sisonke National Movement, which advocates for the rights of sex workers, has been raising the alarm since the closure of US-funded facilities. Before the closures, Sisonke was in talks with National Department of Health through the South African National AIDS Council about the provision of services to sex workers and other vulnerable groups, said the organisation’s spokesperson Yonela Sinqu.
She said that the department never answered activists when they asked what would happen should donor funds no longer be available for these facilities.
She said the plea for assistance without referral letters is made to all provinces, not only Gauteng. However, Gauteng is the only province that has approached us with the crisis of people without referrals, she said.
Department of Health spokesperson Foster Mohale has not responded to requests for comment.
Colourised scanning electron micrograph of HIV (yellow) infecting a human T9 cell (blue). Credit: NIH
Highly effective treatments for HIV have existed since the mid-1990s. But while these treatments keep people healthy, we do not yet have a safe and scalable way to completely rid the body of the virus. In this Spotlight special briefing, Elri Voigt takes stock of where we are in the decades-long search for an HIV cure.
As the science stands, the vast majority of the roughly eight million people in South Africa living with HIV will have to take treatment for the rest of their lives. This is because the antiretrovirals used to treat HIV prevents the virus from replicating but cannot eliminate it from the body. As soon as treatment is stopped, the virus rebounds, resulting in illness and eventually an early death.
A handful of people have been cured of HIV, but these “cures” involve very risky bone marrow transplants given as part of cancer treatment. The harsh reality is that 40 years into the HIV epidemic, and despite major scientific advances, we don’t yet have a viable cure for the roughly 40 million people on the planet who are living with the virus.
The good news, as one will see at any major AIDS conference these days, is that researchers around the world are working very hard to find a cure. In this #InTheSpotlight special briefing, we take a closer look at what progress has been made on this fascinating scientific journey and ask what the possible routes are toward an HIV cure.
What do we actually mean by a cure?
Dr Sharon Lewin, a leading figure in the world of HIV cure research and the inaugural director of the Peter Doherty Institute for Infection and Immunity in Melbourne, explains that a true “cure” for HIV would mean that there is not a single HIV infected cell left in a person’s body.
By contrast, “remission” would mean that the virus is still in the body, but it is being kept under control by the immune system. This could theoretically happen if the amount of HIV infected cells in a person’s body has been reduced to very low levels and the immune system’s ability to control those remaining cells has been enhanced. Basically, Lewin says, it is when the immune system does what antiretroviral therapy (ART) does without needing to take medication. Another term for this is ART-free viral load control.
There are some people living with HIV called “elite controllers” whose immune systems can naturally, without ART, control HIV. There are also extraordinary elite controllers, says Lewin, who through their immune response have been able to get rid of every single piece of the virus that they had in their bodies. Studying what is special about these rare people has been a key area of research in recent years.
Along with concepts like cure, remission, and control, it also helps to understand where vaccines fit in. As Jessica Salzwedel, the senior programme manager for research engagement at New York-based NGO AVAC, explains, a potential HIV vaccine might be therapeutic and not necessarily preventative. A therapeutic vaccine would be given to someone who is already living with HIV, in the hope that the vaccine would prime their immune system to better fight HIV or potentially clear it.
Why don’t we have a viable cure yet?
Finding cures for viral infections is not unheard of. In fact, one of the most consequential medical breakthroughs of the last decade or so was the development of a highly effective cure for hepatitis C. Unfortunately, it seems HIV is a much tougher nut to crack.
HIV works largely by invading a type of immune cell called a CD4 cell. Once inside, HIV writes its own genetic information into the cell’s DNA and then uses the cell’s machinery to produce more HIV. Eventually, the infected CD4 cell bursts and dies. Different types of antiretrovirals work by gumming up different stages of this process by which HIV invades and exploits CD4 cells. Most antiretroviral treatment regimens used today contain two drugs that target two different stages of this process. These medicines can drive HIV replication in the body down to near zero – which is why people who are stable on ART can live essentially normal, healthy lives.
Unfortunately, that is not the full story. As Lewin explains, the virus has a range of “tricks” that allows it to stay in someone’s body for much longer. One of those tricks is that HIV uses one of the immune system’s greatest assets against it. A person’s immune system contains cells that function as an immunological memory – essentially memory cells – which are designed to survive for a very long time. These memory cells, which include special CD4+ (CD4 positive) T-cells, contain information about which antigens it has encountered during a person’s lifetime. This helps the immune system recognise and kill those antigens faster the next time they enter the body.
HIV writes its own genetic code into some of these memory cells, which helps it stay in the body for as long as that person is alive. Lewin explains that once someone is on treatment, these immune system cells infected with HIV go silent and the virus stops replicating. These silent cells that contain infectious virus are rare, about one in every million, and can’t be found easily by the immune system, allowing the virus to hide in an inactive state but still able to release virus should the cell one day be activated.
These memory cells are found mainly in the lymph nodes, although they can also hide away in the gut, the spleen, and even the brain. Collectively, these HIV-infected cells in hiding are known as the latent reservoir. Should someone stop taking antiretroviral treatment, some of the cells in this latent reservoir could reactivate and start replicating again.
Lewin says researchers are getting better at finding these latent HIV-infected cells, but there still isn’t a way to easily tag these cells and destroy them.
Three lines of investigation
According to Lewin, researchers are exploring three broad strategies in search of an HIV cure.
Firstly, with a strategy called “shock and kill”, researchers try to reactivate (shock) the virus in the cells where it is hiding and then destroy (kill) it once it is flushed out. Such an approach will likely require at least two medicines – one to shock and one to kill. Unfortunately, attempts to find treatments that reliably shock HIV-infected cells out of their slumber has not borne much fruit so far.
Secondly, with “block and lock”, researchers hope to permanently silence the HIV that is hiding away in a person’s body. The aim here is to keep HIV latent for good, so that we never need to worry about killing it. This approach might involve using ART together with a latency promoting agent, of which several are currently being researched. “Block and lock” approaches have been picking up momentum in recent years.
Thirdly, with gene editing, researchers aim to “edit” cells to make them resistant to HIV or remove HIV from them. For example, CD4 cells can be modified to not have the specific receptor called CCR5 that HIV requires to gain entry into the cell. Essentially, if you remove the CCR5 receptor from a cell, HIV has no way in and the cell becomes immune to HIV. In this area, there have been some tantalising developments, but nothing yet that amounts to a workable cure. For example, in one study, people had their blood drawn, the CCR5 receptors removed from the CD4 cells in the blood, and then had the blood reinfused. It worked somewhat, but not nearly well enough to call it a cure.
These three categories are not the only way to think about potential cures.
Broadly, we can think about there being two big “buckets” of approaches for an HIV cure, says Salzwedel. The first “bucket” of approaches targets the virus, and those approaches are trying to remove HIV from the cell or “silencing” it so even if it is still present there is no replication. The other “bucket” of approaches looks at the host – or the person living with HIV – and improving their immune system so it can adequately kill HIV or make the cells that have HIV in them easier to spot so these cells can’t hide from the immune system. She says a combination of approaches from both “buckets” will probably need to be used for a cure.
A resource of HIV cure trials maintained by Treatment Action Group, a New York-based advocacy organisation, lists hundreds of clinical trials currently underway that are trying these different approaches or combinations of approaches.
What about the people who have been cured?
As mentioned earlier, one area of research has involved trying to understand “elite controllers”. Another critically important group of people in the search for a cure are the seven or so people who were living with HIV, but who have been cured. Some of these people, like Timothy Ray Brown and Adam Castillejo, have become minor celebrities in the HIV world.
Lewin explains that people like Brown and Castallejo, both of whom have essentially no HIV left in their bodies, had to go through interventions that can’t be replicated in everyone. Both had a type of blood cancer and were living with HIV. They had to undergo chemotherapy which wiped out their bone marrow, including the cells that had HIV in them. They were then given a whole new bone marrow system through a donation from someone who was naturally resistant to HIV since their CD4 cells do not have CCR5 receptors. This allowed the latently infected cells to be “flushed out” of their bodies. One of the other people cured of HIV received a bone marrow transplant from umbilical cord blood.
Such transplants are not things you can do for everyone who is living with HIV, its expensive and the severe risks of the procedure can only be taken in people living with both HIV and certain cancers. Even so, these cases, says Salzwedel, has shown us that it is possible to cure HIV and made us aware of some of the challenges.
Lewin says that cases like those of Brown and Castallejo helped advance gene editing approaches because they showed that not having CCR5 receptors makes CD4 cells essentially immune to HIV. This led to studies using special gene scissors – a technique called CRISPR – to find the gene for the CCR5 receptor in cells and remove it. CRISPR has also been used experimentally to remove HIV from cells.
So far only a small number of studies have been conducted using CRISPR-based gene editing approaches in an attempt to cure HIV – and these were mostly in the lab or in mice and monkeys. The first human gene editing study for CCR5 was done ex vivo – meaning cells were taken out of the body, edited, and then reinfused into the body. The first clinical trial of CRISPR for HIV in vivo – meaning it is done inside the body – is currently underway and early results were presented in July at the AIDS 2024 conference. While initial results in monkeys were promising, the early findings in humans were disappointing. EBT-101, the specific type of CRISPR treatment, did not prevent HIV from returning once treatment was stopped – although one study participant’s HIV only started replicating again after 16 weeks. A longer follow-up study is currently open in the United States for enrolment.
Gene editing could also potentially be used to strengthen the immune system. This could work, Lewin explains, by inserting a new gene that produces an antibody against HIV into cells and then putting those cells back into the body. “So instead of giving an infusion of an antibody, your own body makes the antibody. And that’s been done successfully in people with HIV on ART in two separate clinical trials and more recently in infant monkeys where ART was stopped,” she says. “The investigators injected CRISPR that delivered two different antibodies to infant monkeys who are infected with a monkey adapted form of HIV virus and on ART. The infant monkey’s muscle cells then start making the antibodies, and when they stopped ART, the antibodies kicked in and kept the virus under control, so that’s the most successful type of gene therapy,” Lewin says.
Boosting the immune response
Another promising avenue is broadly neutralising antibodies (bNAbs) – the broadly refers to the ability of these antibodies to neutralise a range of different HIV viral strains. Broadly neutralising antibodies can work as an antiviral while present in the body, but they can also trigger the immune system to control the virus and, according to Lewin, figuring out how bNAbs do this is a very important part of current cure research. Broadly neutralising antibodies that are HIV specific, work by binding with the virus and eliminating it while also enhancing a person’s immune system so it can control the virus that remains in the body by hiding in the immune system’s memory cells. Broadly neutralising antibodies potentially have this beneficial effect on immune control by activating CD4 and CD8 responses – part of the immune system’s defence – to kill HIV cells. There have been several clinical trials where a subset of participants who have been given bNAbs have been able to control the HIV virus for six months after stopping ART and when the bNAbs are no longer detected in blood. The scientific challenge is that this beneficial effect was only seen in a subset of participants and the duration of control is not fully understood as most clinical trials only assess participants up to 24 weeks off of ART.
Lewin says a small study has also looked at using anti-PD1, an antibody that reverses immune system exhaustion and essentially “revs” up the immune system to keep fighting HIV. Early study findings were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) this year. Participants stopped ART and were given four doses of the antibody, called Budigalimab, or placebo over 29 weeks. Six out of the nine people who received the antibody had delayed viral rebound and/or ART free control, and two people had viral control off ART for over 29 weeks. The antibody will now be evaluated in a larger study.
Additional approaches, according to Dr Daniel Douek, an expert in immunology and the Chief of the Human Immunology Section at the National Institute of Allergy and Infectious Diseases in the United States, include HIV vaccines, which so far have not generated a strong enough immune response to be considered successful. Douek was speaking on an IAS webinar on HIV cure research. Another promising approach is to start someone on ART as quickly as possible after infection in the hope of preventing the establishment of the latent reservoir.
Suppressing the immune system with a drug has also been tried, says Douek, and research so far in this area warrants further investigation. While it seems counterintuitive, the researchers wanted to see if suppressing immune system cells might stop or reduce HIV replication because the virus likes to replicate in activated immune cells. People living with HIV, even when on treatment have a lot of activated immune cells. The drug Ruxolitnib, which is used to treat graft-versus-host disease in transplant patients, was given to 60 people living with HIV alongside their HIV treatment. After five weeks, there was a decrease in markers of immune activation and cell survival. And between five and 12 weeks of using this combination, those with large viral reservoirs displayed signs that their reservoirs were reducing in size. However, Douek cautioned that much more work needs to be done before we can draw firm conclusions about the value of this approach .
What comes next?
Though we don’t yet have a viable cure for HIV, Lewin says a lot of progress has been made, especially over the decade and a half since Brown was cured. We now know a lot more than we did about the virus and how it hides away in cells. Today, she says, we have cure interventions that work well in monkeys and some interventions being investigated in human clinical trials have induced ART-free viral control in some participants. But she is also clear that it will probably be “a very long time” before you can go to your doctor and get an HIV cure.
In this #InTheSpotlight special briefing, we have focused on the science, but as we have learnt from the new hepatitis C cures and from HIV prevention injections, the journey from the lab to your local clinic can be a very long one and involves far more than just the science.
According to Lewin, a successful HIV cure will have to tick several boxes. She says one needs an intervention that is durable, so that it leads to ART-free viral load control over a prolonged period of time. At this point, an intervention that allows for control over two, three or five years, is seen as worthwhile. Although the ideal would be to give something once and have ART-free viral load control over a lifetime. The intervention also needs to be scalable, so it can be given to a lot of people. It also needs to be cheap.
And if there is one insight we’ve gained over our many years covering HIV, it is that affordability and sufficient supply are not things we can take for granted. Given that many of the potential cures involve treatments that are substantially more complicated to produce and administer than antiretrovirals, the challenges here might be more acute than what we’ve seen before.
That we will eventually get a cure is also by no means inevitable. This is why it is critically important that governments and philanthropies continue to invest in cure research and support programmes such as the International AIDS Society’s Toward an HIV Cure initiative. Among others, this initiative is helping to build the capacity needed to conduct cure research in low-and-middle income countries.
Right now, even under a best-case scenario, a world without a cure will mean that many millions of people will still be living with HIV until late in the 21st century. A successful cure could change this trajectory. Ultimately, Salzwedel is right when she says: “We can’t really end an epidemic without a cure”.
Although South Africa has the largest number of people living with HIV worldwide, strides have been made in controlling the epidemic, especially in the reduction of HIV incidence, testing, and treatment. Researchers from the South African Medical Research Council (SAMRC) and University of KwaZulu-Natal (UKZN) are inching closer to finding the answer to the natural control of HIV infection, leading to improved health outcomes and quality of life amongst South Africans.
According to the latest survey by the Human Sciences Research Council, in 2022, there were approximately 7.8 million people afflicted with HIV in South Africa, the highest absolute number of people living with HIV globally. Yet despite having the largest genetic diversity in the world, African human genome sequences represent the lowest of all the human genomes that have been sequenced worldwide. There is a dire need to leverage genomics to back up and scale targeted intervention programs to put more people living with HIV on effective treatment.
Of particular interest in the global investigations into HIV is “elite controllers” (ECs), a rare group of HIV‐1‐positive individuals whose immune systems can seemingly suppress the infection from developing without taking antiretrovirals (ARVs). For every 200 people living with HIV, around one may be an elite controller (0.5%). In South Africa, with its high rate of HIV infection, the prevalence of ECs also appears to be higher. By “unmasking” the secrets of ECs through research, clues can be revealed, and new therapies potentially developed to benefit broader groups of people living with the disease.
In order to identify the polymorphism and mutations within individuals of African descent, and understand how they are associated with HIV disease progression, Dr Veron Ramsuran, Associate Professor at UKZN, and Prof Thumbi Ndung’u, Director for Basic & Translational Science at the Africa Health Research Institute, joined hands with SAMRC, MGI and local South African clinics in 2019 to take their 20+ years of work in EC research to the next level using whole genome sequencing (WGS).
“The HIV Host Genome project was started at the same time as we launched SAMRC’s African Genomics Centre in Cape Town with the support from MGI,” said project co-investigator Rizwana Mia, also co-founder of the SAMRC Genomics Centre and Senior Program Manager in Precision Medicine at SAMRC. “The partnership saw MGI putting down a high-throughput sequencing workflow and assisted us with the specialised scaled infrastructure design in our lab. This was at a time when there was no real infrastructure for large-scale next generation sequencing in Africa.”
“More importantly, by moving our laboratory workflow to scale, we are hoping to develop genomic research to address this quadruple burden of disease that South Africa faces,” explained Mia. “Our project looks at a unique cohort of patients that have the ability to control the HIV virus to ascertain how disease progresses and the host-directed mechanisms for innate immune control. In addition, we included family sets to help us better understand the relationship between pediatric non-progressors and their parents who are also HIV positive, to uncover and genetic differences that may contribute to host immune control of HIV.”
“We’ve identified new genes and polymorphism that are playing a role with HIV disease through new data generated from Whole Genome Sequencing,” said Dr Veron Ramsuran, principal investigator of the HIV Host Genome project. “Traditionally, there is a list of mutations or genes that are known to associate with HIV, yet they are largely based on studies on Caucasian populations. Our HIV research is adding to the general pool of knowledge pertaining to individuals of African descendent, which will thereby inform new treatment and new vaccine opportunities.”
“What’s important is also understanding how drugs interact with the individual,” added Ramsuran. “We’ve found in the past that certain polymorphism is associated with drug metabolism in genes. Building on this understanding of drugs in combination with the genetics of the individual, we can develop prediction tools to inform clinicians on drug type or dosage depending on the presence of the polymorphism to facilitate a more rapid metabolism of the drug.”
Encouragingly, investigations into Africa’s diseases will continue beyond this point. The HIV Host Genome project has laid the groundwork for the ambitious National 110K Human Genome Project. This large-scale population study will involve 110 000 participants from the South African population, aiming to understand more about of their genomic diversity, address various health challenges, and pave the way for personalized medicine in the country. Furthermore, the data collected will be incorporated into a national population database, enhancing research outcomes and deepening disease understanding for Africa.
Given South Africa’s diverse population, limited human genomics data and significant healthcare burden from diseases such as HIV, understanding pathogenesis and inherent mutations is important for implementing targeted treatments and public health programs. With its lower sequencing cost, high quality data, and efficient all-in-one workflows, MGI’s equipment play an instrumental role , will continue to drive progress in studying rare HIV phenotypes, which holds great promise in advancing the development of targeted interventions and cures– not only for HIV – but many other diseases.
“Looking at the genetic variation and its impact on HIV is a gamechanger, because it will shed light on some of the best immune responses that can be generated against the HIV virus,” stated Prof Thumbi Ndung’u, principal investigator of several of the project’s cohort studies. “And actually, this knowledge will be widely applicable and could have an impact on other diseases – infectious and non-infectious – as well as their drug interventions. It will make sure that Africans, just like everybody else, are at the centre of drug and vaccine development.”
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.
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.”
A study on almost 4000 people of African descent has identified a gene that acts as natural defence against HIV by limiting its replication in certain white blood cells. The findings were published in Nature. An international effort co-led by EPFL, Canada’s National Microbiology Laboratory, and Imperial College London, it paves the way for new treatment strategies.
“We searched for human genetic variation that associates with spontaneous control of HIV and identified a novel region in the genome that is only variable in populations of African ancestries,” says Professor Jacques Fellay at EPFL’s School of Life Sciences. “We used a combination of computational and experimental approaches to explore the biological mechanism behind the genetic association and provide evidence that the gene CHD1L acts to limit HIV replication in a subset of white blood cells.”
HIV is still a problem
Despite significant advances in treatment and access to therapy, the human immunodeficiency virus remains a global health challenge with almost 40 million affected individuals, no vaccine and no cure.
Although annual HIV infections have been declining because of widespread antiretroviral therapies, the trend has slowed substantially since 2005, and there are now alarming increases in the number of newly infected adults in some regions.
Genome-Wide Association Studies, or GWAS, analyse the entire genome of a large number of individuals to identify genetic variants associated with a clinical outcome, such as the ability to naturally control viral replication.
Measuring HIV replication control: not enough in African populations
The degree of viral infection is measured by the virus’ “setpoint viral load” (spVL), which refers to the relatively stable level of HIV replication in the body after the initial, acute phase of infection in untreated individuals.
A critical determinant of HIV infection progression and transmissibility, spVL is expressed as the number of viral copies/mL of plasma. The spVL of HIV varies widely in the infected population, depending on the ability of every individual’s immune system to control viral replication without antiretroviral drugs.
Although there have been large studies of spVL control in populations of European descent, much less has been done in populations of African ancestries, which have both a high genomic diversity and the greater burden of HIV.
A key gene for resistance to HIV replication in people of African ancestries
To address this disparity, a large international collaboration of scientists and clinicians has now performed large-scale GWAS using data from diverse populations of African ancestries. In total, the scientists analyzed the genomes from 3,879 individuals living with HIV-1. Using computational analysis and fine-mapping techniques, they identified a novel region in the genome that shows a strong association with spVL control.
This region corresponds to a gene known as CHD1L (for “Chromodomain Helicase DNA Binding Protein 1 Like”), which encodes a protein that helps DNA unwind after it has been damaged, allowing it to be repaired. But in this study, the CHD1L gene showed genetic variation specific to populations of African ancestries, and that was linked to the spontaneous control of the most common and virulent type of HIV, called HIV-1.
Having identified CHD1L as a potential modulator of HIV-1 infection, the researchers explored the biological mechanism behind the genetic association and determined that CHD1L plays a role in limiting HIV replication in a subset of white blood cells.
The study was co-led by Jacques Fellay at EPFL, Paul McLaren at the Public Health Agency of Canada’s National Microbiology Laboratory, and Manjinder Sandhu at Imperial College London.
The discovery of CHD1L’s role in limiting HIV replication could lead to improved treatment options for infected individuals. “Our findings provide insights into potential therapeutic targets, which are needed to continue the fight against HIV-1,” says Fellay. “In addition, our results underscore the importance of performing genomic studies in diverse ancestral populations to better address their specific medical needs and global health inequities.”
Making the case for governments and donors to pump money into the HIV response has become more difficult over the last decade. This is partly a result of the notable successes we’ve had – for example, in 2022, HIV-related deaths in South Africa were down to less than a fifth of what it was in 2005. There is clearly some justification for the point of view that HIV simply isn’t the crisis it used to be.
That said, it is also true that about 8 million people in South Africa are living with HIV. This number will continue to rise in the coming years as the rate of new HIV infections is much higher than the rate of HIV-related deaths. Barring a major scientific breakthrough, all these millions of people will require antiretroviral medicines for the rest of their lives, both for their own health and to reduce onward transmission of the virus. In this context, a failure to maintain and improve HIV treatment and prevention programmes will have catastrophic consequences.
There is also increasing competition with other areas of urgent need. In recent years, climate change and COVID-19 have understandably made the headlines much more frequently than HIV. There is also a slow shift underway in South Africa’s disease burden, away from HIV and tuberculosis toward non-communicable diseases (NCDs) such as diabetes and hypertension.
Still a no-brainer
Despite these shifts, there is good reason to think that spending money on HIV continues to offer excellent value for money. For example, according to a recent report by Economist Impact (part of the Economist group that also publishes the Economist magazine), for every dollar spent on HIV in South Africa from 2022 to 2030, it is estimated the country will see GDP gains of over $7.
We also have a good idea of the impact and cost-effectiveness of specific HIV-related interventions. According to the most recent version of the South Africa HIV investment case, published in December 2021, condom provision continues to be the most cost-effective intervention in South Africa, followed by antiretroviral treatment, infant testing, pre-exposure prophylaxis for men who have sex with men, and general population testing. Voluntary medical male circumcision has become less cost-effective as coverage levels have risen in recent years, but remains worth it. In fact, the investment case leaves no doubt that most of the key interventions needed to combat HIV in South Africa are both worth it and affordable.
Despite all this, according to a recent UNAIDS report, global investment in HIV has taken a knock in recent years, and in 2022 we were essentially back down to the same level as in 2013. Such reductions constitute a crisis in HIV funding, especially in poor countries that are heavily reliant on donor funds. In South Africa, key interventions like antiretroviral treatment and condoms generally remain funded, but public sector health budgets have been shrinking in real terms, something that is no doubt impacting the HIV programme.
Time to leverage HIV investments
This brings us back to the knotty problem with which we started – while HIV remains a large and serious problem and most investments in combatting HIV remain excellent value for money, making the case for these investments has become more difficult due to competing priorities and the fact that, in South Africa at least, people are not dying of AIDS at nearly the rate they did 20 years ago. How to best make the case in a way that convinces governments and donors to put up the money in this context is a devilishly hard problem.
There are certainly no simple solutions.
What there is, though, is some indications that a too narrow focus on HIV is becoming a harder sell. There is also a risk that as funds for HIV get harder to come by, and the clamour for funding NCDs becomes more pronounced, we may end up pitting diseases against each other in a way that benefits no one.
Given the incredible acuteness of our HIV crisis ten and 20 years ago, a laser focus on HIV was right and necessary. Today, however, the reality is that many people living with HIV are also living with NCDs like diabetes or hypertension, something that will become only more so as the population of people living with HIV grow older. It is clear that we need to start doing a better job of integrating care and treatment for all the different diseases one person might have – the key is to do so in a way that doesn’t drop the ball when it comes to HIV.
In some areas progress is already clear – medicines distribution via pickup points closer to people’s homes were fuelled by the need to get ARVs to people, but is now also being used to distribute medicines for some NCDs. In other areas, such as data systems, integration however remains limited and the systems available for HIV and TB remain superior to those for NCDs.
There appears to be a broader policy shift along these lines. As recently reported on Devex, the Global Fund to Fight HIV, TB, and Malaria’s current five-year strategy explicitly endorses and promises funding for integrating non-communicable disease services with TB and HIV programmes. UNAIDS’s new ‘The path to end AIDS’ report also makes the right noises on the “deeper integration of HIV and other health services”, as does South Africa’s National Strategic Plan for HIV, TB, and STIs 2023 – 2028.
Of course, the road from policy-level ambitions such as these and change on the ground can be a long one – to some extent such integration has been on the cards for over a decade. But, rising NCD rates, an ageing population of people living with HIV and comorbidities, and funding pressures mean that getting integration right is now more urgent than ever.
One of the arguments for HIV-specific funding has always been that HIV investments have benefited healthcare systems more generally, even if that was not the primary intention. Maybe in this next act of the HIV response then, the key will be to stop thinking of health system improvement as a side effect of HIV investments and instead lean into the idea of explicitly leveraging what we’ve done and will continue to do in HIV to improve health systems more generally.
Several sessions at the 11th SA AIDS conference, recently held in Durban, highlighted the worrying fact that key HIV numbers such as treatment coverage are much lower in children than in adults. There is hope, however, that new treatments and new treatment guidelines might help close the gap.
In a plenary session, Dr Sandile Buthelezi, Director General of the National Department of Health, told delegates that on UNAIDS’ 95-95-95 targets, children in South Africa are at 81-65-68. This means that 81% of children living with HIV have been diagnosed, 65% of those diagnosed are on antiretroviral treatment, and 68% of those on treatment are virally suppressed. For the South African population as a whole, the numbers are at 94-76-92.
Throughout the conference, various speakers highlighted the fact that only 65% of children who have been diagnosed are on treatment as a particular concern. To close the gap and reach UNAIDS’ target of 95%, just over an additional 88 000 children would need to be initiated on treatment.
Professor Lee Fairlie, Director of Maternal and Child Health at Wits RHI, said in a presentation that only 52% of children younger than 14 living with HIV are on treatment. Fairlie also pointed out that children lagged behind substantially when it comes to viral suppression, and this is particularly challenging in the youngest age groups.
Not all bad news
But it was not all bad news at this year’s conference. One piece of good news is that new and better child-friendly antiretroviral formulations are being rolled out in South Africa. These new treatments should make it easier for children to start and stay on treatment – children often find it difficult to take medicines formulated for adults, due to factors like incorrect dosing, large pills, and bad taste.
The National Department of Health recently updated the country’s antiretroviral treatment guidelines to allow for the use of several of these new formulations and better HIV treatment regimens for children. Most notable is the introduction of a new regimen consisting of the medicines abacavir, lamivudine and dolutegravir (ALD for short).
Speaking at the conference, Dr Leon Levin, a paediatrician who has been treating infants, children, and adolescents living with HIV for almost three decades, pointed out that the availability of new paediatric formulations had a major impact on the new treatment guidelines. (Spotlight previously reported on the registration of some of these new formulations here.) Levin is also the Senior Technical Advisor in Paediatrics at the NGO Right to Care.
One such child-friendly formulation is a 120/60mg scored, dispersible tablet of abacavir and lamivudine that can be taken in patients who weigh between 3 and 25kg. It is given once daily and two generics are registered with the South African Regulatory Authority (SAHPRA). “It’s going to literally replace all the other paediatric Abacavir+3TC formulations. You can swallow it, chew it, crush it, or dissolve it in water. So [it’s] very versatile,” he said.
Also important is a paediatric formulation of the antiretroviral dolutegravir – a medicine that forms the backbone of HIV treatment in adults. According to Levin, the child-friendly version of dolutegravir is not available to everyone yet, and many clinicians still need to undergo training on how to use it. It is a 10mg dispersible, scored tablet given once daily that can be used at 3kg and higher and from four weeks of age onward. There are two generic versions of this product registered with SAHPRA.
The introduction of paediatric dolutegravir is likely to overshadow the introduction of a four-in-one formulation of abacavir, lamivudine, lopinavir/ritonavir. The four-in-one combination has to be taken twice daily, is strawberry flavoured and comes in a powder form. “Unfortunately, this product to nobody’s fault was launched at the same time as paediatric dolutegravir. Which means paediatric dolutegravir is going to take centre stage and this product unfortunately is not going to be used much,” Levin said.
Updated guidelines
Levin explained that the changes to South Africa’s treatment guidelines focused on doing two main things when it comes to children living with HIV, the first is to implement an optimised regimen – the ALD regimen and the second is to create an “enabling environment to support engagement in care and adherence”. He said that with the new guidelines, we can expect “much improved [viral] suppression, optimised regimens, improved synchronisation of clinic visits, happier patients and their families and clinicians as well”.
A big change to the guidelines is that now children who weigh 3kg and are four weeks of age should be started on the ALD regimen, instead of the abacavir, lamivudine, and lopinavir/ritonavir regimen that was previously recommended. “This is a major change. It’s a fantastic, well-tolerated regimen. It’s potent and you’re going to get around a lot of the issues you had with these younger children,” Levin said.
Once the children on this regimen get to 30kg, they will be switched to a regimen containing tenofovir, dolutegravir, and lamivudine (TLD for short). TLD is also the regimen adults living with HIV in South Africa are offered when starting treatment for the first time.
For children who are already on treatment, the new guidelines recommend that all children who are four weeks of age and older and weigh 3kg or more should be transitioned to a dolutegravir-containing regimen. For children with suppressed viral loads, the switch to ALD or TLD is straightforward, while for children without viral suppression, it can get more complicated.
Another important change is that children over five years of age are now eligible for Repeat Prescription Collection Strategies (RPCs) if they are virally suppressed and had an age-appropriate disclosure, which means that their HIV status has been explained to them in a way that is appropriate for their age, as outlined in the guidelines. For children under five, they can be given a three months supply at a time, providing they are at least six months old. Levin pointed out that whenever RCPs or a three months supply is considered for children, it is essential to look at where and how the parents may be receiving their own antiretroviral treatment so that it can be co-ordinated, and parents don’t have to go to two different places to collect the medications.
New options in the pipeline
While the paediatric formulations included in the new guidelines are a step forward, there are experimental treatments in the pipeline that may make treatment yet more convenient for children.
“There’s a rich pipeline of new combinations and drug delivery developments. Hopefully, this will further improve access, clinical and virological outcomes,” Fairlie said in a conference presentation. “Obviously, the paediatric market is extremely small and then one has to maintain enthusiasm for manufacturers to actually continue to look at the paediatric population. And so, merging of treatments and prophylaxis regimens is really what would work going forwards.”
In her presentation, she specifically referred to long-acting formulations of cabotegravir (CAB-LA) and rilpivirine (RPV). CAB-LA has already been approved by SAHPRA for HIV prevention in adults and, as Spotlight reported last week, pilot projects evaluating how to best provide the CAB-LA injection in South Africa are set to start soon. The combination of CAB-LA and rilpivirine injections has been approved for the treatment of HIV in adults by the United States Food and Drug Administration, but not yet by SAHPRA. The injections are administered every two months.
Fairlie says that currently there are several studies either ongoing or set to start soon for the use of these agents in the paediatric and adolescent age groups. In addition, there are also trials planned to test another long-acting medication called lenacapavir in adolescents and broadly neutralising antibodies (bNAbs) in children.
She also highlighted several improved delivery methods that are in the pipeline for paediatrics. These include a mechanism that doesn’t require water, like oro-dispersible tablets, also known as fast melts, which disintegrate in the mouth as well as oral films that stick to the mouth, disintegrate there, and dissolve. There are also various tablet options that are small enough for children to swallow easily. Like multi-particulates, which are small and solid, multiple-unit dosages that can take the form of granules, pellets, or beads. Mini-tablets are also a prospect – these are compressed tablets no larger than 4ml. Finally, there are novel mechanisms like long-acting oral drug delivery systems and micro-array patches. Fairlie explained that long-acting oral drugs are where a drug is stored in the centre of a capsule that has a number of “arms”, which are able to keep the capsule in the stomach and slowly dissolve and release the drug into the stomach. This allows for slow-release dosing. The “arms” tend to break down after about seven days.
