OHSU-led discovery in animal model could advance quickly to clinical trials in people
Research from the lab of Jonah Sacha, PhD, at OHSU, has identified a one-time regimen of therapies for newborns with HIV that, if given within three days of birth, could permanently clear the virus. The research team hopes to use the animal model results to move into a human clinical trials. (OHSU/Christine Torres Hicks)
Every year, more than 120 000 newborns worldwide contract HIV, a global health burden that requires lifelong treatment for millions of people – assuming they have access and can afford it. New research led by Oregon Health & Science University suggests another possibility: a one-time regimen of therapies given to newborns within three days of birth to permanently clear the virus. The research was published in the journal Nature Microbiology.
“The really exciting part is that it could go to clinical trials immediately to eliminate HIV infection in newborns,” said co-lead author Jonah Sacha, PhD, professor and chief of pathobiology and immunology at OHSU’s Oregon National Primate Research Center and Vaccine and Gene Therapy Institute. “The next step after that is to test if this can work in newly exposed adults.”
The research involved many collaborators and nonhuman primates at both the Oregon and California national primate research centres.
Researchers tested three distinct treatments that were delivered for a few weeks: neutralising antibodies, standard antiretroviral therapy, and an experimental monoclonal antibody known as leronlimab.
Each of the individual treatments has been tried previously and failed to permanently clear the virus – and Sacha wasn’t convinced combining them would work any better. Sacha has worked for years to develop leronlimab, which is designed to block HIV from entering immune cells through a surface protein called CCR5. His longtime OHSU colleague and coauthor Nancy Haigwood, PhD, thought combining existing therapies with leronlimab might be effective.
The study that published today shows she was correct.
Haigwood, a former professor and ONPRC director, is a virologist and immunologist who has specialised in HIV antibody research for decades. “We were astounded and overjoyed, actually,” Haigwood said. “It’s a remarkable result.”
Antiretroviral therapy has already been approved in people, whereas broadly neutralising antibodies and leronlimab are both being tested separately in clinical trials. This new discovery of a one-time, three-part regimen to clear the virus in newborn babies would first need to be tested in clinical trials in people – most likely in newly exposed adults initially – before it would be widely available to constrain an HIV epidemic that continues to kill 600 000 people worldwide each year.
Researchers say they are optimistic, given the anatomical similarity between nonhuman primates and people.
“There was no reason to think this would completely clear the virus,” Sacha said. “It’s one of those things where you test it and, holy cow, it works and you’ve discovered something new.”
Exactly how this approach worked remains unclear, but Sacha and Haigwood said it appears that the combination of therapies is far more potent and effective than each therapy alone. The key appears to be leronlimab’s ability to block HIV from entering immune cells through the surface protein CCR5.
“For reasons we don’t understand, HIV really wants to use CCR5 receptors to infect cells,” Sacha said. “By blocking access, it’s like you’ve kept fuel away from the fire.”
Haigwood uses a slightly different analogy:
Turning off the faucet: Antiretroviral therapy doesn’t eliminate HIV altogether, but it minimises its ability to replicate.
Mopping up: Neutralising antibodies effectively corral HIV so there is less virus circulating in the body’s blood supply.
Sealing off: Leronlimab blocks what’s left of the virus from infecting immune cells – the equivalent of sealing off the room with a water-tight valve.
Haigwood believes the combination appears to be especially potent early in the infection.
“There’s a lot more going on during the first week of infection than we previously thought,” she said. “From this experiment, it looks like there’s a dynamic interaction between the virus and antibodies that takes place as the virus begins to spread.”
Researchers are eager to see whether the combined regimen can be effective beyond 72 hours of the initial infection.
“We only tested out to three days,” Sacha said. “Could it work a week after infection? Two weeks? How far can you go after infection, and still purge the virus?”
Taking antiretroviral therapy as recommended has expanded the lifespan of people with HIV. (Photo: Unsplash)
By Elna Schütz for Spotlight
South Africa’s first set of clinical guidelines focused on older people living with HIV has been released. They offer practical steps in a resource-strained health system to take care of an ageing patient population.
The guidelines are particularly important in South Africa since the country has an ageing population of people living with HIV. Many of these people would only have started treatment relatively long after they contracted the virus, largely because of the government’s reluctance to make antiretroviral treatment available in the early 2000s. The sooner people start treatment after infection, the better their long-term prognosis tends to be.
In 2025, there were around 1.9 million people over the age of 50 living with HIV in South Africa, according to Thembisa, the leading mathematical model of HIV in the country. This is 24% of the estimated 7.9 million HIV positive people in the country. The 1.9 million figure is more than double the 800 000 people over 50 who were living with HIV in 2015. This number is projected to rise to over 3.6 million by 2035.
Most people over the age of 50 who are living with HIV contracted the virus before they turned 50. The increase depicted in this graph is thus mainly a function of people who are already living with HIV ageing into the over 50 age group. Some people over 50 do become newly infected with HIV, but those numbers are comparatively small.
The changing make-up of the population of people living with HIV, coupled with the fact that antiretroviral therapy has been crucial for clearing and suppressing HIV in the body was a core driver for developing the new guidelines, Dr Camilla Wattrus, the Clinical Director at the Southern African HIV Clinicians Society, tells Spotlight. She is one of the guidelines’ authors.
“Antiretroviral therapy has expanded the lifespan of people with HIV, but we must now also consider how to preserve the ‘health span’ in this group,” says Wattrus.
She explains that this means increasing the years that are spent in good health with a good quality of life.
Another co-author of the guidelines, Nomathemba Chandiwana, Chief Scientific Officer at the Desmond Tutu Health Foundation, points out that after antiretroviral treatment was introduced in South Africa, the life expectancy of people living with HIV increased dramatically. “We didn’t think people would live as long as they have now, so that’s been a big success,” she says. “But now we have new problems.”
Chandiwana says that older people living with HIV have around 16 fewer years in good health than people without HIV. The 16-year figure (technically 15.3) seems to originate in a study published in 2020 in the JAMA medical journal that compared the health and lifespans of insured people with and without HIV in the United States. For people with HIV who started antiretroviral treatment when they were still healthy (CD4 countes above 500), the difference in healthy years was 9.5 years.
Another broad concern is that clinicians may be focused on HIV-related issues like viral suppression for these patients and not be sufficiently aware of other ageing-related developments. People with HIV get the same ageing related diseases as other people, but there is evidence that they tend to get them earlier.
We know from Thembisa model outputs that on average, people living with HIV today are slightly more likely to die of non-HIV-related causes than AIDS. According to the model, there were 53 000 HIV-related deaths in the year from mid-2024 to mid-2025. This is a thousand fewer than the 54 000 people with HIV who died of non-HIV-related causes over the same period.
What is in the new guidelines
The new guidance states that it is designed to:
Raise healthcare workers’ awareness of the needs and concerns of the population of people living with HIV who are 50 years and older.
Inform healthcare workers about an ageing-related approach to older people with HIV.
Highlight good practices to help healthcare workers provide optimal care for this population.
Provide resources about ageing with HIV for healthcare workers, their patients and their patients’ carers.
Guide clinical settings in implementing geriatric care into HIV clinical practice.
The clinical advice in the guidelines follow the World Health Organisation’s (WHO) principles for Integrated Care for Older People (ICOPE), which emphasises prevention prior to frailty, person-centred assessment, and the involvement of healthcare workers other than doctors.
The guidelines cover a thorough list of challenges faced by older people with HIV that need to be monitored and addressed. For instance, physiologically, there is a risk of comorbid conditions like hypertension and cancer, and an increased risk of complications from polypharmacy, when more than five medicines are used concurrently. Social and behavioural challenges include that older people are perceived to be less likely to get infected with HIV and therefore have lower rates of HIV testing and use of HIV prevention tools.
This population is also at risk of being disregarded or not fully cared for in the healthcare system. The guidelines give examples such as restricted mobility access to health facilities and healthcare workers being unaware of the HIV-related risks in older people. “The health system needs to be equipped to manage their needs in a holistic and integrated way, and that is what this guideline aims to support,” says Wattrus.
The guidelines include a comprehensive schedule of what need to be assessed and screened and at what regularity. There is a particular focus on geriatric syndromes like frailty, cognitive impairment, and managing comorbid non-communicable diseases.
“The idea is that every visit with an older patient involves more than just routine HIV care and that it becomes a conversation about how that person is functioning and living,” says Wattrus.
The guidelines also emphasise how care can be offered by a variety of healthcare providers, depending on the resources available. “Recommendations enable task-shifting, which is a practical necessity in a country where specialists such as geriatricians are scarce, and the bulk of HIV routine care is delivered by healthcare workers at primary care level,” says Wattrus.
Even though the guidelines focus on overall health in older people living with HIV, managing HIV is, of course, a part of this. It cautions that “CD4 recovery may be slower and blunter compared to younger individuals,” but viral suppression is still the primary treatment goal.
The crucial factor here is to choose the correct antiretroviral treatment regimen for the patient. For instance, popular tenofovir disoproxil fumarate (TDF) combinations should be avoided in people at risk of or with osteoporosis, bone fractures, or renal impairment. Regimens with tenofovir-alafenamide or abacavir may be better, though the latter is contraindicated if there is high cardiovascular risk.
The new local guidelines hit largely the same notes as a major commission on HIV and ageing that was published by the journal Lancet HIV to coincide with the AIDS 2026 conference taking place in Rio de Janeiro, Brazil.
“Supporting healthy ageing requires more than sustained viral suppression; it requires care that is informed by what matters most to the individual, with attention to maintaining physical and mental function, minimising healthcare complexity, and addressing multimorbidity, polypharmacy, stigma, and social determinants of health,” the commission found.
Simple systems, big change
Apart from giving healthcare workers a framework for giving better care to older people living with HIV, the guidelines advise how this larger change in the health system can happen for this growing older population. “What is great is that most of the recommendations are not complicated or expensive,” says Wattrus.
She explains that the sensitisation and training of healthcare workers, especially in primary care, is a crucial first step. If they know how to, they can easily incorporate brief screenings, such as those for frailty, into normal appointments. For example, as Chandiwana points out, several geriatric tests need only a chair for the patient to sit down on and get up from. She says it is easier to do these things for people with HIV during their existing appointments, compared to people without HIV who may not be visiting health facilities for regular screenings.
Another relatively easy adaptation is to simply make healthcare services easier to access. “This can be done by having appointments aligned across conditions, fewer unnecessary referrals and genuine attention to broader aspects of their health such as poverty, isolation and limited mobility,” she says.
Chandiwana also suggests that one could consider rolling out geriatric care health cards to track screening, as is often done with children. She would also like to see more community buy-in, in a similar way as there was during the earlier part of the HIV treatment roll-out. For instance, she suggests community health clubs and increased health literacy efforts around ageing.
Avoiding problematic polypharmacy, says Wattrus, is another low-cost, high-yield strategy that does not require specialist input. “Routinely reviewing medication lists, identifying unnecessary drugs, and checking for interactions is straightforward and can make a significant difference,” she says.
More specialists would of course help. Chandiwana says there are fewer than 50 geriatric specialists in the country. She says there is also a much wider need for geriatric-specific training across the healthcare system, including for primary care nurses and community healthcare workers.
Lastly, Chandiwana says the guidelines offer a much-needed look into the unique challenges and needs of older people with HIV as an opportunity for the government to act to prevent a future problem. “So that investment in having scalable, simple systems for people who are ageing, both with HIV and without, I think, would be fantastic, but that needs money,” she says.
The LiU researchers have shown that HIV exhausts the body’s immune system by overactivating it, despite effective antiviral treatment. Photo: Charlotte Perhammar
HIV exhausts the body’s immune system by overactivating it, despite effective antiviral treatment. Researchers from Linköping University have conducted cell studies showing that an existing medication restores immune cell function. The findings raise hopes that this medication could improve the health of people living with HIV.
For people living with HIV, antiviral treatment is effective in limiting the amount of virus in the blood and slowing the progression of AIDS. But the virus can stay hidden in the body for many years and contribute to premature ageing of the immune system. Despite effective treatment, the immune system is commonly impaired in people with HIV. Linköping University researchers therefore investigated how the virus causes dysregulation of the immune system.
In healthy people infected with a virus, a protein called type I interferon is activated that plays a very important role in the body’s immune system. Type I interferon is the first protection against viral infections and also ensures that other parts of the immune system kick in. Once the infection is combated, the amount of type I interferon falls back to a very low level.
In their study, the researchers show how HIV exploits the body’s type I interferon signalling to drive chronic immune activation, also when the virus is under control due to medication.
“In the case of an HIV infection, type I interferon provides protection in the first stage when the body gets infected. But if the interferon is chronically activated, an overactivation of the immune system will instead facilitate the spread of HIV in the body,” says Cecilia Svanberg, postdoctoral fellow at Linköping University and lead author of the study, published in the journal PLOS pathogens.
May be treateable
A chronically activated immune system eventually leads to several different types of cells in the immune system becoming exhausted and less effective. Two important cell types affected are dendritic cells and T cells.
The researchers’ experiments on human cells showed that the chronic activation of interferon occurs precisely when dendritic cells and T cells are in contact with each other. This opens up an opportunity to restore immune cell function.
“When we treated the cells with a medication currently used to treat another disease, this perfectly restored the function of the immune cells. It looks just like when HIV is not present,” says Cecilia Svanberg.
The medication, anifrolumab, blocks type 1 interferon and is used to treat systemic lupus erythematosus, SLE, an autoimmune disease. Other research groups have conducted studies on animals with HIV-like infections, treating them with either anifrolumab or other substances with the same function. The amount of HIV virus in the blood has decreased and the animals’ health has improved.
“Using this interferon blocker together with existing antiviral treatment could possibly improve the health of people living with HIV. We think it would be worth investigating further,” says Marie Larsson, professor of virology at Linköping University, who led the study.
If someone living with HIV is not on antiretroviral therapy, the virus can cause inflammation in, among other places, the brain. Photo by Anna Shvets
By Biénne Huisman
Antiretroviral therapy has shifted HIV from a fatal to a chronic condition. But neuropsychiatrists say it is imperative for people living with the virus to start treatment immediately as the “duration of untreated exposure” may cause irreversible brain damage and impact long-term cognitive health.
It has been recognised for decades that cognitive impairment is a potential complication of HIV infection. Questions over how likely and how serious this potential complication is have become more urgent over time as the population of people living with HIV ages – ageing after all also increases the risk of cognitive decline.
There were around 1.75 million people over the age of 50 living with HIV in South Africa in 2024, according to Thembisa, the leading mathematical model of HIV in the country. This is just over 20% of the estimated eight million HIV positive people in the country. A study published in the Lancet medical journal also has the number at around 20% in sub-Saharan Africa.
This is a delicate field of enquiry as researchers walk a tightrope to avoid “the burden of double stigma”, while conceptualising the necessary tools to best diagnose brain problems and suitable interventions.
Within as little as two weeks
At Groote Schuur Hospital’s Neuroscience Institute, Professor John Joska, director of the University of Cape Town’s (UCT’s) HIV Mental Health Research Unit, explains that HIV can enter the brain within as little as two weeks after the initial infection – primarily through infected white blood cells, such as lymphocytes. If a person is not on antiretroviral therapy, the virus can cause inflammation in the brain and possibly also tissue damage.
“The brain is a protected compartment,” says Joska. “A theory as to how the virus, which is a protein particle, gets into the brain is through infected lymphocytes. This doesn’t directly infect nerve cells, what we call neurons. It infects other supporting tissues and cells in the brain, causing an inflammation which damages typically the white matter of the brain. Over time, that inflammation can cause loss of neurons, but indirectly.”
While antiretroviral therapy is crucial for clearing and suppressing HIV in all body compartments, including in the brain, he says that it does not reverse damage that occurred before the treatment was started.
“Today, people with HIV are living near normal lifespans,” he says. “The question is, will the fact that they’ve had HIV, with some duration of untreated exposure and potential loss of brain tissue, cause them to be at higher risk than the average person for developing dementias of old age – which really are mainly Alzheimer’s disease or vascular dementia.” It is these longer-term effects that are the main concern when it comes to the impact of HIV on the brain.
Part of the problem is that South Africa not only has an ageing population of people living with HIV, but many of these people would only have started treatment quite long after they contracted the virus. One key reason for this is the South African government’s reluctance to make antiretroviral treatment available in the early 2000s. It has been estimated that those delays resulted in over 300 000 avoidable deaths – they may also be contributing to brain health issues now and in the future.
From efavirenz to dolutegravir
Apart from HIV itself, some of the medicines used to treat the infection have also had an impact on the brain.
In 2019, the standard HIV treatment in South Africa changed from a three-drug combination containing an antiretroviral drug called efavirenz, to a combination containing the drug dolutegravir. This shift had mental health benefits, as evidenced in research lead by Joska’s fellow UCT Neuro-HIV researcher, Associate Professor Sam Nightingale.
Joska says: “The study looked at the period from 2017 to 2020 and the switch from efavirenz to dolutegravir based treatment. It was well known that efavirenz caused, certainly for the first two months, a bunch of psychotropic or psychological issues like nightmares or anxiety, even psychosis for some people. But our findings showed people who switched to dolutegravir actually do very well. They look more like people without HIV after eight months. So dolutegravir has been a huge advantage, not only because it’s robust, but because it’s neuro-protective.”
New models for HIV and cognitive impairment
A shift is underway in how experts are thinking about cognitive impairment in people with HIV. Some neuropsychiatrists, including Joska, are recommending a shift away from the 2007 HIV-Associated Neurocognitive Disorders model, arguing that its cognitive test scores do not adequately account for variables such as education and socioeconomic background, and that it can overdiagnose impairment. The argument is set out in an article, lead-authored by Nightingale, that was published in the journal Nature Reviews Neurology in 2023.
The authors argue that a label of cognitive impairment might cause a “double burden of stigma” for people living with HIV – affecting self-esteem, inciting fear and prompting further discrimination against persons already subject to stigma as it stands. To illustrate the point, they point out how, up until recently, people with HIV in the United Kingdom could not become airline pilots due to concerns over cognitive impairment. However, following a campaign by a pilot living with HIV, the United Kingdom’s Civil Aviation Authority removed the ban in 2022.
Nightingale and his colleagues argue that traditional test scores be used in conjunction with real-life symptoms and medical evidence of brain problems. It introduces the conceptual model of HIV-Associated Brain Injury, which refers specifically to damage caused by the virus. This distinguishes it from other causes of cognitive impairment such as depression, substance abuse, diabetes and cardiovascular disease. As Spotlight previously reported, HIV is also associated with an increased risk of depression, though this is at least partially driven by social factors.
Lower cognitive function associated with late diagnosis
At the 2026 Conference on Retroviruses and Opportunistic Infections hosted in Denver in the United States in late February, these issues were tabled at a discussion titled “When I’m 64: Neurodegeneration, Epigenetic Aging, and Cognition in Older People With HIV.”
Professor John Joska is the director of the University of Cape Town’s HIV Mental Health Research Unit. (Photo: Biénne Huisman/Spotlight)
In his presentation, Professor Alan Winston of Imperial College London, also a member of the International HIV-Cognition Working Group, and a frequent co-author alongside Joska and Nightingale, relayed existing research findings that on average, people living with HIV have lower cognitive function – including memory, attention span and executive function like planning – compared to people who don’t have HIV of the same age. He said that this manifests as an increased risk of lower grade early dementia.
Like Joska, Winston stressed that the most deteriorated cognitive function in people living with HIV is associated with untreated HIV and late HIV diagnosis. He reiterated that starting HIV treatment soon after diagnosis is protective, and that viral suppression is associated with better cognition. In groups of patients with HIV well controlled on dolutegravir-based HIV treatment, cognition appears similar to HIV negative groups, he said.
HIV clinicians need to pay better attention to the brain
In an impassioned presentation, Dr Shibani Mukerji, Associate Professor of Neurology at Harvard Medical School, argued that protecting the brain is an overlooked frontier in effective HIV treatment, and that clinicians need to pay more attention to it.
“By the time patients and clinicians notice cognitive decline – generally and in HIV – the damage to the brain is done and lives are affected negatively. People don’t raise cognitive concerns early enough due to stigma, fear, [and] lack of recognition of the issues. It is seen as ‘just getting old’,” she said.
Mukerji emphasised the need to prioritise brain health. “HIV doctors and treatment programmes are focused, almost exclusively, on viral load as the marker of successful treatment. They may be thinking laterally and consider TB and other infections, maybe cardiovascular disease – but they are definitely not paying enough attention to brain health. HIV doctors aren’t aware enough of brain health issues in people living with HIV, and even when they are, they often don’t feel comfortable diagnosing or managing it, so it is under recognised and under diagnosed.”
The perception that there is no way to manage or treat cognitive decline –generally and in people living with HIV – is wrong, she said, adding that optimising physical, mental and social health is critical for brain health.
“Almost half of dementia risk [in people in general] is linked to preventable causes,” she told conference delegates, along with a slide listing preventable causes including loss of hearing, social isolation, cardiovascular disease and depression.
She explained: “If someone has cognitive decline and for example you improve their hearing – if they have hearing issues – and you work on their social isolation, and treat their vascular disease, and treat their depression, you can see a marked improvement in their cognition.”
Ending her presentation with a twist of humour, Mukerji’s last slide referred to the session’s title, a reference to the Beatles song on aging “When I am 64”. She printed the song’s lyrics: “When I get older, losing my hair, many years from now…”, closing her talk by saying: “It’s okay to stand up and sing, in fact your doctor might prescribe it.”
Cipla Medpro South Africa reaffirmed its commitment to ensuring the uninterrupted supply of critical antiretroviral (ARV) medicines to the Department of Health. It is essential that people living with HIV have uninterrupted access to these life-saving medicines. Any disruption of supply puts patients at risk of developing resistance to the drugs or adversely affecting health outcomes. According to Statistics South Africa, the number of people living with HIV in the country is estimated to be approximately 8 million (12,7% of the population)[1].
Recently, two suppliers who were awarded the current antiretroviral (ARV) tender, Barrs Pharmaceuticals Industries (Pty) Ltd and Innovata Pharmaceuticals (Pty) Ltd (subsidiaries of Avacare Health), have entered business rescue.
Cipla acknowledges the uncertainty this may create within the ARV supply chain and underscores its readiness to assist in maintaining stability and continuity.
Cipla has been manufacturing tenofovir/lamivudine/dolutegravir (TLD) for the government for the past 7 years, and has been one of the main suppliers of ARVs to the government for more than 12 years. Cipla has made significant investments in its local manufacturing facility, upgrading the capacity of the ARV production line with the installation of a new Countec bottle line and have increased its tablet filing capacity by 190%. The company is able to locally produce 475 million tablets annually and has upscaled its manufacturing capabilities to ensure sufficient capacity to meet current demand and support near‑term growth, while reinforcing Cipla’s commitment to secure and reliable ARV supply.
“We have mobilised resources to help maintain equitable access to quality, affordable critical medication. Cipla confirms its willingness to support national requirements under the current tender agreement and, if needed, contribute meaningfully to any supplementary procurement processes to safeguard patient access to essential treatment. We want people to live a long and healthy life as part of our commitment to caring for life,” said Paul Miller, CEO of Cipla Africa.
“In addition, we believe this tender presents an opportunity to further advance government’s commitment to strengthening local manufacturing capacity. By ensuring greater support for locally produced medicines, future allocations could meaningfully contribute to South Africa’s industrial development agenda while maintaining continuity of supply,” said Miller.
The total ARV tender is for a period of three years, and is worth an estimated R15.5bn, of which the TLD component comprises R12.6bn.
This is the first study using a combination of immunotherapies in humans. The results show promise for sustained control of the virus.
Colourised scanning electron micrograph of HIV (yellow) infecting a human T9 cell (blue). Credit: NIH
A new study from UC San Francisco shows it may be possible to control HIV without long-term antiviral treatment – an advance that points the way toward a possible cure for a disease that affects 40 million people around the world.
Treatment with a combination of experimental immunotherapy agents enabled 7 out of 10 participants to keep the virus at low levels for many months after going off antiretroviral therapy (ART).
The results appear on Dec. 1, World AIDS Day, in Nature.
The trial, which relied on a collaboration with nearly a dozen pharmaceutical companies and other partners in HIV research, offers a proof of concept that the approach could work. Although the study was small and did not include a control arm, investigators said the results are extremely encouraging.
“The majority had some evidence of control, which we believe is unprecedented,” said the paper’s co-senior author, Steven Deeks, MD, a professor of Medicine at UCSF who is in the Division of HIV, Infectious Diseases, and Global Medicine at Zuckerberg San Francisco General Hospital. “I do believe we are finally making real progress towards developing a therapy that may allow people to live a healthy life without the need of life-long medications.”
The trial was made possible by the Foundation for AIDS Research (amfAR)’s $20 million, five-year partnership with UCSF to advance AIDS cure research, launched in 2015. It was also supported by the National Institutes of Health (NIH).
Reprogramming the body’s immune system
Antiretroviral therapy (ART) was introduced in the 1990s and turned HIV infection from a death sentence into a chronic disease. But it is not a cure, and the virus stays in the body ready to reawaken as soon as someone stops taking ART.
The study was designed to test whether a triple combination of immunotherapies could reprogram the body’s immune system to control the virus after going off ART. Most of the participants had started ART soon after they acquired HIV, which helped preserve their immune response.
First, participants received a therapeutic vaccine to encourage their T cells to go after the latent HIV in their bodies. Then, they received an antibody cocktail to reduce the amount of HIV in the body. Finally, they were given another round of anti-HIV antibodies before being taken off ART.
Typically, when a person with HIV stops HIV medicines, the virus starts to rebound in about two weeks and then skyrockets. This time, only three of the 10 patients experienced the typical rapid rebound. Six maintained low levels of the virus for months, and one did not rebound at all.
The pouncing cat analogy
The investigators then examined the immune responses of those who controlled the virus to see how they did it.
“It turns out the controllers had T cells that were able to expand dramatically once they ran into the virus,” said Rachel Rutishauser, MD, PhD, an associate professor in UCSF’s Division of Experimental Medicine and co-senior author of the paper. “It’s like they were hanging out waiting for their target, kind of like a cat getting ready to pounce on a mouse.”
The treatment would need to be simplified and proved effective in much larger studies before it could replace standard HIV treatment.
“This is not the end game,” said Michael Peluso, MD, an assistant professor in UCSF’s Department of Medicine and the study’s first author. “But it proves we can push progress on a challenge we often frame as unsolvable.”
Eastern Cape HIV Programme demonstrates success in resource-constrained setting
Photo by Pexels on Pixabay
A new randomised controlled trial conducted in the Eastern Cape has shown that adding structured patient navigation to same-day antiretroviral therapy (ART) can make a meaningful difference for people newly diagnosed with HIV. The trial found that patients who received support from trained navigators were far more likely to stay in care and keep their viral load low over six months. Those with navigator support had a 79% retention rate, compared with 64% under standard care.
Among patients who achieved a viral load of fewer than 50 copies per millilitre, 64% remained in care, compared to just 39% without this extra support(1). Patient navigation combines personal support, such as home or virtual check-ins and WhatsApp reminders, with practical help like linking people to services and monitoring their progress. It was especially effective for people who started treatment on the same day as their diagnosis.
“This approach humanises HIV care. It builds a bridge between the clinic and the community, helping patients stay connected to treatment and ultimately saving lives,” said lead author Siyakudumisa Nontamo, Facility Team Lead: Care & Treatment Programme at TB HIV Care.
In August 2024 the Human Sciences Research Council released findings from the Sixth South African HIV Prevalence, Incidence, and Behaviour Survey (SABSSM VI) for the Eastern Cape. The results show that HIV prevalence in the province stabilised, moving from 15.9% in 2017 to 13.7% in 2022. This is an estimated 980 000 people living with HIV, down from about 1 million in 2017. Access to treatment has improved significantly. ART coverage increased from 67.8% in 2017 to 83.5% in 2022, meaning about 723 000 people in the province are now receiving treatment. However, gaps remain among young people: only 70.9% of adolescents and youth aged 15–24 living with HIV are on ART, compared to 84.8% of adults aged 25-49. Among females, coverage is much lower for young women (68.7%) than for women aged 25-49 (88.2%). ART use also varies across districts, ranging from 69.4% in Nelson Mandela Bay to 92.0% in Alfred Nzo(2). Nationally, the proportion of people living with HIV who are currently on antiretroviral treatment (ART) rose to 80.9% in 2022, up from 63.7% in 2017.
Despite major advances in antiretroviral therapy, retention in care remains a persistent challenge within South Africa’s HIV programme, especially in rural provinces such as the Eastern Cape. Many patients initiate treatment but later disengage due to stigma, transport difficulties, and limited ongoing support. The study shows that low-cost, human-centred interventions can significantly strengthen treatment outcomes. The trial, titled “Impact of Patient Navigation on Retention in Care and HIV Viral Load Suppression Among Newly Diagnosed Persons Living with HIV in the Eastern Cape,” compared standard HIV care to an approach where trained patient navigators provided ongoing support to patients starting antiretroviral therapy (ART). Beyond improved retention and viral suppression, the trial also showed that patients supported by navigators experienced fewer deaths and dropouts, with substantially lower losses to follow-up and reduced mortality than those receiving standard care, ultimately strengthening HIV programmes(1).
Patient navigation, in particular, helps bridge the gap by pairing practical healthcare coordination with empathy and community-based follow-up. Navigators assist patients with managing appointments, maintaining adherence, and accessing psychosocial services, thereby fostering trust, continuity, and sustained engagement in care. This approach aligns with South Africa’s national HIV strategy, which prioritises differentiated, patient-centred models of care to achieve the UNAIDS 95-95-95 targets.
At scale, TB HIV Care’s programmes are grounded in person-centred, integrated service models that reflect the real lives and needs of people affected by HIV and TB. This study reinforces TB HIV Care’s belief that support beyond clinic walls is essential for achieving lasting impact. In the 2024/25 reporting period, the organisation reached more than 1.9 million people with HIV testing services and initiated 27,873 individuals on ART, achieving a 95% viral suppression rate among clients in care.
“By bridging the gap between diagnosis and ongoing care, patient navigation aligns with our outreach for key populations and our shift toward holistic service delivery. We look forward to translating this evidence into practice, ensuring fewer people fall through the cracks and more sustain treatment success”, said Professor Harry Hausler, CEO at TB HIV Care.
Additional findings from the Sixth South African HIV Prevalence, Incidence, and Behaviour Survey (SABSSM VI) for the Eastern Cape.
In the Eastern Cape, HIV remains most common among adults aged 25-49, with a prevalence of 27.7%, and women in this age group are especially affected at 35.4% compared to 17.1% for men.
The survey also found geographic differences: HIV prevalence among men was highest in urban areas (8.7%), while among women it was highest in rural informal or tribal areas (19.8%).
By district, prevalence was highest in Chris Hani (14.4%), Amathole (14.1%), Alfred Nzo (13.9%), and lowest in Nelson Mandela Bay (9.7%).
At a national level, the survey showed that 81.4% of all people living with HIV were virally suppressed. The survey found encouraging progress in the Eastern Cape, where viral load suppression (VLS) among people living with HIV rose to 79.3% in 2022, up from 66.3% in 2017. However, children aged 0-14 years had much lower suppression levels, at 61.4%. Among people aged 15-49 years living with HIV, 78.6% were virally suppressed. Within this group, women had far higher suppression rates (83.9%) than men (65.4%).
About the Randomized Controlled Trial
The randomised controlled trial involved participants from HIV testing sites in the O.R. Tambo District (Flagstaff, Mthatha Gateway, and Tsolo Clinics). It was approved by the Eastern Cape Health Research Committee and Walter Sisulu University’s Ethics Committee. The study was supported by the Chemical Industries Education and Training Authority (CHIETA) and the South African Medical Research Council’s Strategic Health Innovation Partnerships (SHIP).
References:
Nontamo, S., Kamsu, G.T., Ndebia, E.J., et al. Impact of Patient Navigation on Retention in Care and HIV Viral Load Suppression Among Newly Diagnosed Persons Living with HIV in the Eastern Cape – South Africa. Access.
Human Sciences Research Council. Sixth South African HIV Prevalence, Incidence, and Behaviour Survey (SABSSM VI). Access.
Pharmacists can initiate people with HIV on antiretroviral treatment, the Supreme Court of Appeal has ruled. Photo: GroundUp Staff
The Supreme Court of Appeal (SCA) has dismissed, with costs, an appeal by a doctor’s organisation, the IPA Foundation, aimed at stopping specially trained pharmacists from treating people with HIV and TB.
The IPA first took its dispute with the South African Pharmacy Council (SAPC) to the Gauteng High Court in Pretoria. In 2023, Judge Elmarie van der Schyff ruled in favour of the pharmacists, giving a judicial go-ahead for the council to introduce its Pharmacy-Initiated Management of Antiretroviral Treatment (PIMART) initiative.
However the IPA Foundation, intent on having the initiative set aside, took this ruling on appeal to the SCA. In that court, five judges this week ruled against it. The ruling came nearly 11 months after the case was heard, far more than the three months that judicial norms provide for when a judgment is reserved.
Justice Tati Makgoka, writing for the court, said the initiative was created in response to a persistent rise in new HIV infection rates.
The SAPC, at the department’s request, deemed PIMART suitable for addressing this issue.
“As the high court correctly found, the SAPC evaluated the risks associated with pharmacists initiating first-line ART [antiretroviral treatment] and TPT [tuberculosis preventive therapy] as well as providing medicines for PrEP [Pre-Exposure Prophylaxis of HIV] and PEP [Post Exposure Prophylaxis of HIV], considering the risks when deciding to approve the PIMART training.
“The uncontested evidence presented by the SAPC demonstrates that the approved accreditation process for PIMART was rigorous and thorough,” Makgoka said.
In her previous judgment, Van Der Schyff had noted that a 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 had approached the Pretoria 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.
On appeal, the IPA persisted with these arguments.
Dealing with the background, Justice Makgoka said the SAPC had published a notice in the government gazette in March 2021 regarding the proposed adoption of PIMART, giving interested parties 60 days to comment. This resulted in government approval later that year.
It was only after this that the IPA submitted its comments and objections.
Following engagements, the IPA lodged the review application in the high court.
On the issue that the IPA and its members claimed they were not given sufficient notice of PIMART, because it was advertised in the government gazette during the Covid-19 pandemic – Makgoka said there was no suggestion that the pandemic had “paralysed the administrative functions” of the IPA.
Remarkably, the judge said, the IPA had not suggested that the notice did not come to its attention, finding that adequate notice had been given. Makgoka said that several other organisations had submitted comments during the prescribed period.
He said the IPA had also not challenged the validity of the Pharmacy Act, which specified publication in the gazette and in the absence of that, it was not open for it to say the publication was inadequate.
Makgoka said the IPA had introduced the issue of “rationality” only in its notice of appeal. However, the court had dealt with this because there was no prejudice to the SAPC.
In ruling on this issue, he said PIMART was a crucial intervention in the public interest, which had been devised by a group of medical experts.
“Through PIMART, the SAPC aimed to improve access to healthcare. Contrary to the IPA’s contentions, PIMART is an essential intervention in the fight against HIV/AIDS. Its introduction constitutes a rational legislative and practical measure with the competence of the SAPC as an organ of the state in enhancing access to healthcare for HIV treatment, in fulfilment of the state’s obligation under the Constitution,” Makgoka said.
“These are legitimate and compelling public interests.”
He said the IPA was wrong in believing that PIMART was a blanket licence for pharmacists to treat HIV patients.
“Its scope is limited and applies only to accredited pharmacists. It will not alter the scope of practice for medical practitioners. The fact is that medical practitioners do not have the exclusive rights to care for people living with HIV/AIDS. This is a collaborative effort involving various health professionals.”
The IPA had also submitted that pharmacists were not authorised to prescribe schedule 3, 4 and 5 medicines without a prescription.
However, the judge said, the Medicines Act carved out an exception to this with authorisation of the Director-General. It was through this that PIMART-accredited pharmacists could apply for permits to prescribe schedule 3 – 5 substances.
The appeal was dismissed with costs.
Certainly not all doctors oppose the idea of pharmacists initiating patients with HIV on treatment: the South African HIV Clinicians Society stated: “We look forward to supporting the rollout of PIMART which will further contribute to South Africa’s HIV response and progress towards the 2030 target of eliminating HIV as a public health concern.”
Colourised scanning electron micrograph of HIV (yellow) infecting a human T9 cell (blue). Credit: NIH
For over three decades, HIV has played an elaborate game of hide-and-seek with researchers, making treating – and possibly even curing – the disease a seemingly insurmountable obstacle to achieve.
But scientists at Case Western Reserve University have made a breakthrough discovery that could fundamentally change strategies for treating HIV.
The team identified for the first time how HIV enters a dormant state in infected cells that allows the virus to “hide” from the immune system and current treatments.
The researchers believe the finding, just published in Nature Microbiology, challenges decades of scientific assumptions and opens a new approach to possibly eliminating the deadly virus.
“This discovery rewrites what we thought we knew about how HIV goes into this stealth mode in the human body,” said study lead Saba Valadkhan, an associate professor in the Department of Molecular Biology and Microbiology at the Case Western Reserve School of Medicine. “We’ve shown that HIV actually orchestrates its own survival by reprogramming host cells to create the perfect hiding place.”
The team discovered that HIV uses a clever survival trick that explains why it’s been impossible to cure. After HIV invades a cell, it sneaks its genetic code into the cell’s DNA, then tricks the cell into going to sleep, which also puts the virus to sleep, making both completely invisible. This tactic makes the infected cell invisible to the immune system and unreachable by even today’s most advanced HIV drugs. The virus stays hidden in these dormant cells until the right moment to “wake up” and spread again, creating an undetectable reservoir that ensures HIV never goes away completely.
“What we’ve uncovered is that HIV doesn’t just randomly go dormant – it actively manipulates the host cell to create conditions for its own survival,” said study collaborator Jonathan Karn, Distinguished University Professor and chair of the Department of Molecular Biology and Microbiology. “This gives us specific targets to attack.”
The findings may extend far beyond HIV treatment. The researchers believe similar dormancy actions could be triggered by other viruses – including herpes, hepatitis and other retroviruses – potentially leading to new therapies for many viral diseases.
“We may have uncovered new tactic viruses use to trick the host cells to do their bidding,” Valadkhan said.
This discovery is also important for protecting public health worldwide because viruses like HIV – which can permanently insert themselves into a person’s DNA – could potentially be used as future viral threats and pandemic preparedness.
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.
