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How Much does Our HIV Response Depend on US Funding?

On By ModernMedia
The United States has slashed its HIV funding — through the PEPFAR programme — to African countries. Archive photo: Ashraf Hendricks

By Jesse Copelyn

After the US slashed global aid, the South African government stated that only 17% of its HIV spending relied on US funding. But some experts argue that US health initiatives had more bang for buck than the government’s programmes. Jesse Copelyn looks past the 17% figure, and considers how the health system is being affected by the loss of US money.

In the wake of US funding cuts for global aid, numerous donor-funded health facilities in South Africa have shut down and government clinics have lost thousands of staff members paid for by US-funded organisations. This includes nurses, social workers, clinical associates and HIV counsellors.

Spotlight and GroundUp have obtained documents from a presentation by the National Health Department during a private meeting with PEPFAR in September. The documents show that in 2024, the US funded nearly half of all HIV counsellors working in South Africa’s public primary healthcare system. The data excludes the Northern Cape.

Counsellors test people for HIV and provide information and support to those who test positive. They also follow up with patients who have stopped taking their antiretrovirals (ARVs), so that they can get them back on treatment.

Overall, the US funded 1,931 counselors across the country, the documents show. Now that many of them have been laid off, researchers say the country will test fewer people, meaning that we’ll miss new HIV infections. It also means we’ll see more treatment interruptions, and thus more deaths.

PEPFAR also funded nearly half of all data capturers, according to the documents. This amounted to 2,669 people. Data capturers play an essential role managing and recording patient files. With many of these staff retrenched, researchers say our ability to monitor the national HIV response has been compromised.

These staff members had all been funded by the US President’s Emergency Plan for AIDS Relief (PEPFAR). The funds were distributed to large South African non-government organisations (NGOs), who then hired and deployed the staff in government clinics where there is a high HIV burden. Some NGOs received PEPFAR funds to operate independent health facilities that served high-risk populations, like sex workers and LGBTQ people.

But in late January, the US paused almost all international aid funding pending a review. PEPFAR funds administered by the US Centres for Disease Control (CDC) have since resumed, but those managed by the US Agency for International Development (USAID) have largely been terminated. As a result, many of these staff have lost their jobs.

The national health department has tried to reassure the public that the country’s HIV response is mostly funded by the government, with 17% funded by PEPFAR – currently about R7.5 billion a year. But this statistic glosses over several details and obscures the full impact of the USAID cuts.

Issue 1: Some districts were heavily dependent on US funds

The first issue is that US support isn’t evenly distributed across the country. Instead, PEPFAR funding is targeted at 27 ‘high-burden districts’ – in these areas, the programme almost certainly accounted for much more than 17% of HIV spending. Some of these districts get their PEPFAR funds from the CDC, and have been less affected, but others got them exclusively from USAID. In these areas, the HIV response was heavily dependent on USAID-funded staff, all of whom disappeared overnight.

Johannesburg is one such district. A doctor at a large public hospital in this city told Spotlight and GroundUp that USAID covered a substantial proportion of the doctors, counsellors, clerks, and other administrative personnel in the hospital’s HIV clinic. “All have either had their contracts terminated or are in the process of doing so.”

The hospital’s HIV clinic lost eight counselors, eight data capturers, a clinical manager, and a medical officer (a non-specialised doctor). He said that this represented half of the clinic’s doctors and counselors, and about 80% of the data capturers.

This had been particularly devastating because it was so abrupt, he said. An instruction by the US government in late-January required all grantees to stop their work immediately.

“There was no warning about this, had we had time, we could have made contingency plans and things wouldn’t be so bad,” he explained. “But if it happens literally overnight, it’s extremely unfair on the patients and remaining staff. The loss of capacity is significant.”

He said that nurses have started to take on some of the tasks that were previously performed by counselors, such as HIV testing. But these services haven’t recovered fully and things were still “chaotic”.

He added, “It’s not as if the department has any excess capacity, so [when] nurses are diverted to do the testing and counselling, then other parts of care suffer.”

Issue 2: PEPFAR programmes got bang for buck

Secondly, while PEPFAR may only have contributed 17% of the country’s total HIV spend, some researchers believe that it achieved more per dollar than many of the health department’s programmes.

Professor Francois Venter, who runs the Ezintsha research centre at WITS university, argued that PEPFAR programmes were comparatively efficient because they were run by NGOs that needed to compete for US funding.

“PEPFAR is a monster to work for,” said Venter, who has previously worked for PEPFAR-funded groups. “They put targets in front of these organisations and say: ‘if you don’t meet them in the next month, we’ll just give the money to your competitors’ and you’ll be out on the streets … So there’s no messing around.”

US funding agencies, he said, would closely monitor progress to see if organisations were meeting these targets.

“You don’t see that with the rest of the health system, which just bumbles along with no real metrics,” said Venter.

“The health system in South Africa, like most health systems, is not terribly well monitored or well directed. When you look at what you get with every single health dollar spent on the PEPFAR program, it’s incredibly good value for money,” he said.

Not only were the programmes arguably well managed, but PEPFAR funds were also strategically targeted. Public health specialist Lynne Wilkinson provided the example of the differentiated service delivery programme. This is run by the health department, but supported by PEPFAR in one key way.

Wilkinson explained that once patients are clinically stable and virally suppressed they don’t need to pick up their ARVs from a health facility each month as it’s too time-consuming both for them and the facility. As a result, the health department created a system of “differentiated service delivery”, in which patients instead pick up their medication from external sites (like pharmacies) without going through a clinical evaluation each time. But Wilkinson noted that before someone can be enrolled in that service delivery model, clinicians need to check that patients are eligible.

“Because [the enrollment process] was going very slowly … this was supplemented by PEPFAR-funded clinicians who would go into a clinic and review a lot of clients, and get them into that system”. By doing this, PEPFAR-funded staff successfully resolved a major bottleneck in the system, she said, reducing the number of people in clinics, and thus cutting down on waiting times.

Not everyone is as confident about the overall PEPFAR model. The former deputy director of the national health department, Dr Yogan Pillay, told Spotlight and GroundUp that we don’t have data on how efficient PEPFAR programmes are at the national level. This needs to be investigated before the health department spends its limited resources on trying to revive or replicate the programmes, argued Pillay who is now the director for HIV and TB delivery at the Gates Foundation.

While he said that many PEPFAR-funded initiatives were providing crucial services, Pillay also argued that “the management structure of the [recipient] NGOs is too top-heavy and too expensive” for the government to fund. Ultimately, we need to consider and evaluate a variety of HIV delivery models instead of rushing to replicate the PEPFAR ones, he said.

Issue 3: PEPFAR supported groups that the government doesn’t reach

An additional issue obscured by the 17% figure is that PEPFAR specifically targeted groups of people that are most likely to contract and transmit HIV, like people who inject drugs, sex workers, and the LGBTQ community. These groups, called key populations, require specialised services that the government struggles to provide.

Historically, PEPFAR has given NGOs money so that they could help key populations from drop-in centres and mobile clinics, or via outreach services. All of this operated outside of government clinics, because key populations often face stigma in these settings and are thus unwilling to go there.

For instance, while about 90% of surveyed sex workers say that staff at key populations centres are always friendly and professional, only a quarter feel the same way about staff at government clinics. This is according to a 2024 report, which also found that many key populations are mistreated and discriminated against at public health facilities. (Ironically, health system monitoring organisation Ritshidze, which conducted the survey, has been gutted by US funding cuts.)

While the key populations centres funded by the CDC are still operational, those funded by USAID have closed. The health department has urged patients that were relying on these services to go to government health facilities, but researchers argue that many simply won’t do this.

Venter explained: “For years, I ran the sex worker program [at WITS RHI, which was funded by PEPFAR] … Because sex workers don’t come to [health facilities], you had to provide outreach services at the brothels. This meant … we had to deal with violence issues, we had to deal with the brothel owners, and work out which days of the week, and hours of the day we could provide the care. Logistically, it’s much more complex than sitting on your bum and waiting for them to come and visit you at the clinic.

“So you can put up your hand and say: ‘Oh they can just come to the clinics’ – like the minister said. Well, then you won’t be treating any sex workers.” Venter said this would result in a public health disaster.

He argued that one of the most crucial services that key populations may lose access to is pre-exposure prophylaxis (PrEP), a daily pill that prevents HIV.

While the vast majority of government clinics have PrEP on hand, they often fail to inform people about it. For instance, a survey of people who are at high-risk of contracting HIV in KwaZulu-Natal found that only 15% were even aware that their clinic stocked PrEP.

Another large survey found that at government facilities, only 19% of sex workers had been offered PrEP. By contrast, at the drop-in centres for key populations, the figure was more than double this, at 40%. Without these centres, the health system may lose its ability to create demand for the drug among the most high-risk groups.

One health department official told Spotlight and GroundUp that the bulk of the PrEP rollout would continue despite the US funding cuts. “The majority of the PrEP is offered through the [government] clinics,” she said, 96% of which have the drug.

However, she conceded that specific high-risk groups like sex workers have primarily gotten PrEP from the key populations centres, rather than the clinics. “This is the biggest area where we are going to see a major decline in uptake for [PrEP] services,” she said.

600 000 dead without PEPFAR?

Overall, the USAID funding cuts have severely hindered the HIV testing programmes, data capturing services, PrEP roll-out, and follow-up services for people who interrupt ARV treatment. And the patients who are most affected by this are those that are most likely to further transmit the virus.

So what will the impacts be? According to one modelling study, recently published in the Annals of Medicine, the complete loss of all PEPFAR funds could lead to over 600 000 deaths in South Africa over the next decade.

While South Africa still retains some PEPFAR funding that comes from the CDC, beneficiaries are bracing for this to end. According to Wilkinson, the PEPFAR grants of most CDC-funded organisations end in September and future grants are uncertain. For some organisations, the money stops at the end of this month.

Meanwhile, if the government has any clear plan for how to manage the crisis, it’s certainly not making this public.

In response to our questions about whether the health department would be supporting key populations centres, the department’s spokesperson, Foster Mohale, said: “For now we urge all people living with HIV/AIDS and TB to continue with treatment at public health facilities.”

When pressed for details about the department’s plans for dealing with the US cuts, Mohale simply said that they could not reveal specifics at this stage and that “this is a work in progress”.

In his budget speech in Parliament on Wednesday, Finance Minister Enoch Godongwana did not announce any funding to cover the gap left by the abrupt end of US support for the country’s HIV response. Prior to the speech, Godongwana told reporters in a briefing that the Department of Health would assist with some of the shortfall, but no further information could be provided.

Published by GroundUp and Spotlight.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

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SA Unveils Ambitious New HIV Campaign amid Aid Crisis

On By ModernMedia
Photo by Miguel Á. Padriñán: https://www.pexels.com/photo/syringe-and-pills-on-blue-background-3936368/

By Ufrieda Ho

Amid major disruptions caused by aid cuts from the United States government, the health department aims to enrol a record number – an additional 1.1 million – of people living with HIV on life-saving antiretroviral medicine this year. Experts tell Spotlight it can’t be business as usual if this ambitious programme is to have a chance of succeeding.

Government’s new “Close the Gap” campaign launched at the end of February has set a bold target of putting an additional 1.1 million people living with HIV on antiretroviral treatment by the end of 2025.

Around 7.8 million people are living with HIV in the country and of these, 5.9 million are on treatment, according to the National Department of Health. The target is therefore to have a total of seven million people on treatment by the end of the year. Specific targets have also been set for each of the nine provinces.

The initiative is aimed at meeting the UNAIDS 95–95–95 HIV testing, treatment and viral suppression targets that have been endorsed in South Africa’s National Strategic Plan for HIV, TB, and STIs 2023 – 2028. The targets are that by 2030, 95% of people living with HIV should know their HIV status, 95% of people who know their status should be on treatment, and 95% of people on treatment should be virally suppressed (meaning there is so little HIV in their bodily fluids that they are non-infectious).

Currently, South Africa stands at 96–79–94 against these targets, according to the South African National Aids Council (SANAC). This indicates that the biggest gap in the country’s HIV response lies with those who have tested positive but are not on treatment – the second 95 target.

But adding 1.1 million people to South Africa’s HIV treatment programme in just ten months would be unprecedented. The highest number of people who started antiretroviral treatment in a year was the roughly 730 000 in 2011. In each of the last five years, the number has been under 300 000, according to figures from Thembisa, the leading mathematical model of HIV in South Africa. According to our calculations, if South Africa successfully adds 1.1 million people to the HIV treatment programme by the end of 2025, the score on the second target would rise to just above 90%.

The record for the most people starting antiretroviral treatment in a single year was approximately 730 000 in 2011. (Graph by Spotlight, based on Tembisa data.)

The ambitious new campaign launches at a moment of crisis in South Africa’s HIV response. Abrupt funding cuts from the United States government – the PEPFAR funding – has meant that the work of several service-delivery NGOs have ground to a halt in recent weeks.

These NGOs played an important role in getting people tested and in helping find people and supporting them to start and restart treatment. The focus of many of these NGOs was on people in marginalised but high-risk groups, including sex workers, people who use drugs and those in the LGBTQI community. As yet, government has not presented a clear plan for how these specialised services might continue.

“We will need bridging finance for many of these NGOs to contain and preserve the essential work that they were doing till we can confer these roles and responsibilities to others,” says Professor Francois Venter, of the Ezintsha Research Centre at the University of the Witwatersrand.

He says good investment in targeted funding for NGOs is a necessary buffer to minimise “risks to the entire South African HIV programme” and the looming consequences of rising numbers of new HIV cases, more hospitalisations, and inevitably deaths.

Disengaging from care

South Africa’s underperformance on the second 95 target is partly due to people stopping their treatment. The reasons for such disengagement from HIV care can be complex. Research has shown it is linked to factors like frequent relocations, which means people have to restart treatment at different clinics over and over. They also have to navigate an inflexible healthcare system. A systematic review identified factors including mental health challenges, lack of family or social support, long waiting times at clinics, work commitments, and transportation costs.

Venter adds that while people are disengaged from care, they are likely transmitting the virus. The addition of new infections for an already pressured HIV response contributes to South Africa’s sluggish creep forward in meeting the UNAIDS targets.

The health department has not been strong on locating people who have been “lost” to care, says Venter. This role was largely carried out by PEPFAR-supported NGOs that are now unable to continue their work due to the withdrawal of crucial US foreign aid.

Inexpensive interventions

Other experts working in the HIV sector, say the success of the Close the Gap campaign will come down to scrapping programmes and approaches that have not yielded success, using resources more efficiently, strategic investment, and introducing creative interventions to meet the service delivery demands of HIV patients.

Key among these interventions, is to improve levels of professionalism in clinics so patients can trust the clinics enough to restart treatment.

Professor Graeme Meintjes of the Department of Medicine at the University of Cape Town says issues like improving staff attitudes and updating public messaging and communications are inexpensive interventions that can boost “welcome back” programmes.

“The Close the Gap campaign must utilise media platforms and social media platforms to send out a clear message, so people know the risks of disengagement and the importance of returning to care. The longer someone interrupts their treatment and the more times this happens, the more they are at risk of opportunistic infections, severe complications, getting very sick and needing costly hospitalisations,” he says.

Clinics need to provide friendly, professional services that encourage people to return to and stay on treatment, Meintjes says, and services need to be flexible. These could include more external medicine pick-up points, scripts filled for longer periods, later clinic operating hours, and mobile clinic services.

“We need to make services as flexible as possible. People can’t be scolded for missing an appointment – life happens. Putting these interventions in place are not particularly costly, in fact it is good clinical practice and make sense in terms of health economics by avoiding hospitalisations that result from prolonged treatment interruptions,” he says.

The Close the Gap campaign, Meintjes adds, should reassure people that HIV treatment has advanced substantially over the decades. The drugs work well and now have far fewer side effects, with less risk of developing resistance. More patients are stable on the treatment for longer and most adults manage their single tablet once-a-day regime easily.

Insights from our experiences

Professor Linda-Gail Bekker, Chief Executive Officer at the Desmond Tutu Health Foundation, says to get closer to the target of 1.1 million people on treatment by year-end will mean using resources better.

“Additional funding is always welcome, so are new campaigns that catalyse and energise. But we also need to stop doing the things we know don’t have good returns. For instance, testing populations of people who have been tested multiple times and aren’t showing evidence of new infections occurring in those populations,” she says.

There is also a need for better data collection and more strategic use of data, Bekker says. Additionally, she suggests a status-neutral approach, meaning that if someone tests positive, they are referred for treatment, while those who test negative are directed to effective prevention programmes, including access to pre-exposure prophylaxis (PrEP) for people at high risk of exposure through sex or injection drug use.

But Bekker adds: “We need to be absolutely clear; these people aren’t going to come to us in our health facilities, or we would have found them already. We have to do the work that many of the PEPFAR-funded NGOs were doing and that is going to the last mile to find the last patient and to bring them to care.”

She says the impact of the PEPFAR funding cuts can therefore not be downplayed. “The job is going to get harder with fewer resources that were specifically directed at solving this problem.”

Venter names another approach that has not worked. This, he says, is the persistence of treating HIV within an integrated health system. Overburdened clinics have simply not coped, he adds, with being able to fulfil the ideal of a “one-stop-shop” model of healthcare.

Citing an example, he says: “Someone might come into a clinic with a stomach ache and be vomiting, they might be treated for that but there’s no investigation or follow-up to find out if it might be HIV-related, for instance. And once that person is out of the door, they’re gone.”

Campaign specifics still lacking

The Department of Health did not answer Spotlight’s questions about funding for the Close the Gap campaign; what specific projects in the campaign will look like; or how clinics and clinic staff will be equipped or supported in order to find the 1.1 million people. There is also scant details of the specifics of the campaign online.

Speaking to the public broadcaster after the 25 February campaign launch, Health Minister Dr Aaron Motsoaledi said South Africa is still seeing 150 000 new infections every year. He said they will reach their 1.1 million target through a province-by-province approach. He used the Eastern Cape as an example.

“When you look at the 1.1 million, it can be scary – it’s quite big. But if you go to the provinces – the Eastern Cape needs to look for 140 000 people. Then you come to their seven districts, that number becomes much less. So, one clinic could be looking for just three people,” he said.

Nelson Dlamini, SANAC’s communications manager, says the focus will be to bring into care 650 000 men, as men are known to have poor health-seeking habits. Added to this will be a focus on adolescents and children who are living with HIV.

He says funding for the Close the Gap campaign will not be shouldered by the health department alone.

“This is a multisectoral campaign. Other departments have a role to play, these include social development, basic education, higher education and training, etc, and civil society themselves,” Dlamini says.

The province-by-province approach to reach the target of finding 1.1 million additional people is guided by new data sources.

“Last year, SANAC launched the SANAC Situation Room, a data hub which pulls data from multiple sources in order for us to have the most accurate picture on the status of the epidemic,” says Dlamini.

These include the Thembisa and Naomi model outputs and data from the District Health Information System and Human Sciences Research Council, he says adding that SANAC is working to secure data sharing agreements with other sectors too.

Dlamini however says the health department, rather than SANAC, will provide progress reports on the 10-month project.

Republished from Spotlight under a Creative Commons licence.

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Our HIV Response Will Collapse Without US Funding – Unless We Act Urgently

On By ModernMedia

Reassurances that state clinics will pick up the lost services are empty

Sign outside a Wits RHI clinic in Johannesburg. Photo: Ihsaan Haffejee

By Francois Venter

South Africa faces its worst health crisis in 20 years. Worse than COVID, and one that will overshadow diabetes as a major killer, while pouring petrol on a dwindling TB fire. But it is preventable if our government steps up urgently.

Nearly eight-million people have HIV in South Africa; they need life-long antiretroviral medicines to stay healthy.

The near-total removal of US government funding last week, a programme called PEPFAR, will see every important measure of the HIV programme worsen, including hospitalisations, new infections in adults and children, and death. Unless government meaningfully steps in to continue funding the network of highly efficient organisations that currently fill key gaps in national care, an epidemic that was tantalisingly close to coming under control will again be out of our reach. Millions of people in South Africa will become infected with HIV and hundreds of thousands more will die in the next ten years. 2025 will end much more like 2004, when we started our HIV treatment programme.

Many fail to recognize the danger. Commentators, public health officials, and government spokespeople have downplayed the US financial contributions to the HIV response, suggesting services can be absorbed within current services. The funding cuts amount to approximately 17% of the entire budget for HIV and largely go to salaries for health staff. On the face of it, this indeed seems replaceable. So why are the consequences so deadly?

To understand the impact, one must recognize how US funding has supported HIV care. The money is largely allocated to a network of non-government organisations through a competitive, focused, and rigorously monitored program in four key areas:

  1. Active case finding: The best way to prevent new cases of HIV is find everyone with the disease early on, and get them on treatment. These organisations deploy people in high-risk areas, to test for HIV and screen for TB, and shepherd people who test positive to treatment programmes. People are almost always healthy when they start treatment, and remain healthy, with greatly reduced time to transmit the virus, and much less chance of ever “burdening” the health sector with an opportunistic infection. They are hugely cost-effective.
  2. Tracing people who disappear from care: Patients on antiretrovirals fall out of care for many reasons, ranging from changing their address, to life chaos such as losing their job or mental illness. Or they are simply mixed up in the filing dysfunction within clinics. The US supported programmes helped finding people ‘lost from care’, maintaining systems able to track who has not come back, and how to contact them, often spending considerable time cleaning redundant records as people move between facilities.
  3. Vulnerable population programmes: Services include those for sex workers, LGBTQ+ people, adolescents, people who use drugs, and victims of gender violence. These programs are for people who need tailored services beyond the straightforward HIV care offered in state clinics. They are often discriminated against in routine services and also at significant risk of contracting HIV.
  4. Supporting parts of the health system: This includes technical positions supporting medicine supply lines, laboratories and large information systems, as well as organisations doing advocacy or monitoring the quality of services. All of this keeps the health system ticking over.

In central Johannesburg, where I work, HIV testing services have collapsed. The people who fell out of programmes are not coming back. HIV prevention and TB screening have largely stopped.

Reassurances that state clinics will pick up testing are empty – the staff do not exist, and testing has not resumed. State clinics do not trace people who fall out of care for any illness, let alone for HIV. The data systems maintained by PEPFAR-supported organisations are now gone.

What happens now? The first hard sign that things are failing will be a large drop in the number of people starting treatment, versus what happened in the same month one year ago. The next metric to watch will be hospitalisations for tuberculosis and other infections associated with untreated HIV infection. This will happen towards the end of the year, as immune systems fail. Not long after, death rates will rise. We will see that in death certificates among younger people – the parents and younger adults.

Unfortunately, much of this information will not be available to the health department for at least a year or two, because among the staff laid off in this crisis are the data collectors for the programmes that tracked vital metrics.

The above should come as no surprise, especially to the public health commentators and health department, which is why it is so surprising to hear how certain they are that the PEPFAR programme can easily be absorbed into the state services. The timing of this crisis could not be worse, with huge budget holes in provincial health departments.

Why should this be a priority? After starting the HIV programme in 2004, we spent the next few years muddling through how to deliver antiretrovirals to millions of people in primary care, before we realised we also needed to diagnose them earlier. In 2004, the average CD4 count (a measure of immune strength) at initiation of treatment was about 80 cells/ul, devastatingly low – normal is > 500 cells/ul. A quarter were ill with TB.

This CD4 count average took years to go up, but only by pushing testing into clinic queues, communities, and special services for key populations, not waiting till they were sick. Recently, the average initiation CD4 count was about 400 cells/ul, stopping years of transmission, with most people healthy, and only a small number with TB.

There are many reasons to criticise the relationship between PEPFAR and the health department. It suited both parties to have a symbiotic relationship that meant each got on with their job and ticked their respective output boxes, but neither had to tussle with the messiness of trying to move the PEPFAR deliverables into the health department. As we move forward, learning from these fragilities to plan for the future of the HIV care programme, and for other diseases, will be critical.

Since the suspension of funding, many people have said, “We don’t hear much about HIV anymore”. That is because when the system works well, you don’t hear about it. Some things are far better compared to 2004:

  • We have a government not in denial about HIV being a problem nor encouraging pseudoscience or crackpots.
  • Our frontline health workers, in over 3000 clinics, have vast experience initiating and maintaining antiretrovirals.
  • Antiretrovirals are cheaper, more potent, more durable, and safer.
  • Treatment protocols are simpler.
  • New infection rates are way down.
  • Government delivery systems have improved.
  • Data systems suggest that the majority of ‘lost’ patients are in care, often simply in another clinic.

A sensible emergency plan would do this:

  • Fund existing programmes for a limited time, understanding that the level of reach and expertise is impossible for the health department to replicate at short notice.
  • Couple this with a plan to make posts more sustainable over the next year or two.
  • Learn from the PEPFAR programme that rigorously held organisations accountable, so that provinces can similarly be answerable for their HIV metrics.
  • Ask hard questions why single patient identifiers, and government information systems, that could easily be linked to laboratory, pharmacy and radiology databases, are still not integrated within the public systems, as they are throughout the private health system.
  • Accept that certain key functions and clinics may best be sited outside of the health department.

This will not save the large and valuable research programmes, which need other help. Much of the rest of Africa needs a Marshall Plan to rescue their entire HIV service, as they are almost totally dependent on US government funding.

But ideas like the above will preserve the current South African HIV response and allow us to imagine interventions that could end the disease as a threat for future generations.

No one disputes we need a move away from donor-assisted health programmes. But the scale and immense urgency of this oncoming emergency needs to be understood. We need a plan and a budget, and fast. Or we will have an overwhelmed hospital system and busy funeral services again.

Professor Francois Venter works for Ezintsha, a policy and research unit at Wits. He has been involved in the HIV programme since 2001, and ran several large PEPFAR programmes till 2012. Venter and his unit do not receive funding from PEPFAR, USAID or CDC. Thank you to several experts for supplying analysis and ideas for the initial draft of the article.

Published by GroundUp and Spotlight

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

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US Funding Remains Frozen for Many Life-saving Services

On By ModernMedia

Despite waivers, court judgments and assurances from the embassy, USAID funding for projects that provide HIV medication has not resumed

The Ivan Toms Centre for Health building in Green Point, Cape Town. Photo: Jesse Copelyn

By Jesse Copelyn

Numerous South African health projects funded by the US President’s Emergency Plan for AIDS Relief (PEPFAR) remain closed. This is despite a federal court judgment which ordered President Donald Trump’s administration to lift the blanket freeze on global aid.

A waiver on life-saving humanitarian services appears to have had little effect. Funding remains frozen for many projects that provided services explicitly covered by the waiver, such as antiretroviral (ARV) medicines for people with HIV.

A spokesperson for one of these projects said that the United States Agency for International Development Aid (USAID) had not provided any communication regarding the waiver, despite requests for information.

A second organisation said USAID instructed it to provide an adapted budget that only covers services included in the waiver. The organisation submitted it, but it has not yet been approved. The organisation supports orphaned children living with HIV.

CDC funding

PEPFAR is a US initiative that provides billions of dollars a year toward combating HIV in different parts of the world. These funds are primarily distributed through two agencies: USAID and the Centers for Disease Control and Prevention (CDC).

In late January USAID issued stop-work orders to the organisations which it funds. A few days later, the CDC did the same. This was after an executive order by Trump which paused foreign development funding for 90 days pending a review. As a result, US-funded health organisations across South Africa were forced to close their doors. In some cases, HIV patients were left without ARVs.

Last week the CDC issued notifications to its recipient organisations rescinding the stop-work orders. The CDC stated that this was because of a temporary restraining order issued by a federal judge in Rhode Island that halted the Trump administration’s ability to freeze congressional funds. Since then, many South African organisations that get money from the CDC have reopened.

See also: How USAid freeze sent shockwaves through Ethiopia published in The Guardian

But USAID did not send out similar notifications. PEPFAR funds from this agency largely remain frozen.

In a separate judgment on 13 February, a federal judge in Washington DC blocked the implementation of Trump’s executive order to freeze foreign aid. The administration’s lawyers have argued that the US government can continue to freeze aid via other channels unrelated to the executive order.

Dangerous disruption

GroundUp and Spotlight visited three health centres in South Africa funded by USAID, and found all three remained closed. Representatives from a fourth USAID-funded organisation confirmed that its funding has not been restored, and that its partner organisation was in the same boat.

The first centre that we visited is a clinic in Rosebank, Johannesburg, run by OUT LGBT Wellbeing. It provided free HIV testing, ARVs, and the daily HIV-prevention pill (this is referred to as Pre-exposure Prophylaxis or PrEP). It’s one of several US-funded clinics that OUT operates around the country.

Its services are geared toward men who have sex with men. The reason is that rates of HIV are high among this group, and stigma may prevent some from seeking help in general healthcare settings.

When we visited the centre in Rosebank, a note was tied to the gate, stating: “Regrettably our clinic is temporarily closed and consequently no health services are available”. It encouraged patients to go to their nearest health facility.

According to OUT spokesperson Luiz De Barros, the clinics were forced to halt immediately after stop-work orders were issued. This prevented them from making alternative plans, leaving many people without ARVs or PrEP.

He said the centres had a total of 84 staff, who are now “at home without pay”, and about 5000 clients. Without their ARVs, De Barros worries that many clients are at risk of falling ill or developing drug-resistant HIV. Stopping HIV prevention services like PrEP will also “heighten the spread of HIV within communities,” he noted.

De Barros said they had not yet received any communication from USAID about the limited waiver, despite asking for information.

A clause in the waiver says it does not apply to “gender or DEI [diversity, equality and inclusion] ideology programs”. The Trump administration has not spelled out exactly what these terms mean, but it appears that DEI includes any health project which targets particular groups, like LGBTQ people.

GroundUp and Spotlight visited a second health centre in Hillbrow run by the WITS Reproductive Health Institute (RHI). A sign on the gate stated: “USAID has served the WITS RHI Key Populations Programme a notice to pause programme implementation. As of Tuesday, 28 January, we are unable to provide services until further notice.”

WITS RHI’s annual reports suggest that USAID has previously sponsored its projects to treat and prevent HIV, including among high-risk groups like sex workers and transgender people.

The third health facility that we visited is the Ivan Toms Centre for Health, based in Green Point, Cape Town. A temporary closure notification hung from the door. The centre provided HIV and TB testing, ARVs, PrEP, and counselling services – all focused on men who have sex with men.

Representatives from a fourth organisation, NACOSA, told GroundUp and Spotlight that it had been forced to halt all of its USAID-funded services. Subsequently, USAID instructed the organisation to provide a revised budget which only includes activities listed under the waiver. As part of this limited budget, NACOSA proposed retaining a project which helps orphaned and vulnerable children living with HIV in the Western Cape.

Dr Ntlotleng Mabena, a technical specialist at NACOSA, said the project provides these children with psychological support and connects them to health providers. Clinical workers linked to the ANOVA health institute (which is also US-funded) provide the children with ARV treatment, she said.

NACOSA submitted the revised budget with the hope of restarting this service, but they are still awaiting approval. Mabena stated that ANOVA was also waiting for permission to continue. In the meantime, the service remains closed.

The US embassy in South Africa maintains that Trump’s funding cuts do not affect PEPFAR initiatives that provide life-saving services as defined in the limited waiver.

Yet all of the life-saving PEPFAR services that we investigated on Thursday are closed. The only services which have reopened are those funded by the CDC, which is unrelated to the waiver.

Sign outside a Wits RHI clinic in Johannesburg. Photo: Ihsaan Haffejee

Published by GroundUp and Spotlight

Correction on 2025-02-21 12:29

Three paragraphs were removed from the article after publication because of confusion that arose as to whether they were on the record or not.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

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Categories : Healthcare Politics and Regulations HIVTags :

SA Health Research Facing Catastrophic Financing Cuts

On By ModernMedia
Professor Ntobeko Ntusi is the president and CEO of the South African Medical Research Council. (Photo: SAMRC)

By Catherine Tomlinson

Cuts to United States funding of health research could have “catastrophic” consequences, says Professor Ntobeko Ntusi, who is at the helm of the country’s primary health research funder. He says the South African Medical Research Council is “heavily exposed” to the cuts, with around 28% of its budget coming from US federal agencies.

After an unprecedented two weeks of aid cuts by the United States government that left HIV programmes and research efforts across the world reeling, the Trump administration took the drastic step of freezing aid to South Africa in an executive order on 7 February.

The order – which is a directive to the executive branch of the US government and holds the weight of law – was issued to respond to what the White House called “egregious actions” by South Africa. It specifically points to the Expropriation Act and the country’s accusation of genocide against Israel at the International Court of Justice as the primary reasons for the funding freeze.

While there are some limited wavers and exceptions to the cuts, Spotlight understands that these have so far been poorly communicated and many HIV services remain in limbo.

The funding cuts, following an earlier executive order issued on 20 January,  are interrupting critical health research underway across South Africa and will ultimately undermine global efforts to stop HIV and TB.

The US is a major source of financing for health research in South Africa. Many of the country’s research institutes, groups, and universities receive funding from the US through the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), USAID, and the President’s Emergency Plan for Aids Relief (PEPFAR).

Over the past few weeks, these funding sources have come under siege by the Trump administration resulting in a gaping, and most likely insurmountable financing gap, for many health research endeavors in the country.

US spending accounts for just over half (55%) of all spending on global health research around the world. In 2022, the super power spent $5.4 billion on global health research, according to Impact Global Health –  an NPO that tracks health research spending.

While the US gives money to global health research through several different government departments and programmes, the largest source of funding for global health research is the NIH. The NIH contributed 65% of global financing for HIV research between 2007 and 2022, according to Impact Global Health and 34% of tuberculosis research financing in 2023, according to New York-based policy think tank, the Treatment Action Group.

South Africa has the biggest HIV epidemic in the world in absolute terms and is among the top 10 countries in terms of TB cases per capita.

Catastrophic consequences

“South Africa is the biggest recipient of NIH funding outside of the US”, Professor Ntobeko Ntusi, president and CEO of the South African Medical Research Council (SAMRC), told Spotlight. “[T]he consequences will be catastrophic if [funding] is stopped… for science that is important for the whole world,” he said.

South Africa plays a critical role in advancing HIV science, said Ntusi, adding that “many of the major trials that have advanced our understanding of both the effective strategies for HIV management, as well as understanding the mechanisms of disease emanated from South Africa”.

People in the US, for example, are now able to access long-acting HIV prevention shots, largely because of research that was conducted in South Africa and Uganda. Research conducted in South Africa has also been critical to validating new tuberculosis treatments that are currently the standard of care across the world.

Heavily exposed

Stop work orders were sent to research groups receiving USAID funding at the end of January. These stop work orders coupled with the halting of funding have already interrupted critical HIV research efforts, including efforts to develop new vaccines against HIV.

Ntusi said that the SAMRC is currently “heavily exposed” to the halting of grants from USAID and the CDC, with research programmes supported by USAID and the CDC already being stopped.

The SAMRC’s research on infectious diseases, gender-based violence, health systems strengthening, as well as disease burden monitoring are also affected by the funding cuts.

“In addition to support for HIV research, we have significant CDC grant funding in our burden of disease research unit, the research unit that publishes weekly statistics on morbidity and mortality in South Africa,” said Ntusi. “Our health systems research unit has a number of CDC grants which have been stopped [and] in our gender and health research unit we had a portfolio of CDC funding which also has been stopped.”

Along with programmes being impacted by the halting of USAID and CDC funding, Ntusi said there will also be major staffing ramifications at the SAMRC as well as at universities.

He said that if funding from the NIH is stopped “there would be huge fallout, we just wouldn’t be able to cover the hundreds of staff that are employed through the NIH granting process”.

The SAMRC’s combined annual income from US grants (NIH, CDC and USAID) is 28% of its total earnings (including both the disbursement from the SA government as well as all external contracts) for the 2025/2026 financial year, according to Ntusi. “So, this is substantial – effectively a third of our income is from US federal agencies,” he said.

Pivot away from infectious disease?

In addition to the executive order freezing funding to South Africa, it is unknown whether the NIH will remain a dominant funder of global health. Robert F. Kennedy Jr., the US health secretary nominee, has called for cutting to the NIH’s infectious disease research spending to focus more on chronic diseases.

Looking beyond health, Ntusi said the executive order halting aid to South Africa will be felt across a range of different development initiatives such as water and sanitation, and climate change.

Republished from Spotlight under a Creative Commons licence.

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Categories : HIVTags :

Decoding How HIV Hijacks our Cellular Machinery

On By ModernMedia
Colourised transmission electron micrograph of an HIV-1 virus particle (yellow/gold) budding from the plasma membrane of an infected H9 T cell (purple/green).

A team of scientists at the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg and the University of Regensburg has unveiled insights into how HIV-1 skilfully hijacks cellular machinery for its own survival. By dissecting the molecular interplay between the virus and its host, the researchers identified novel strategies that HIV-1 employs to ensure its replication while suppressing the host’s cellular defences. The study was published in the journal Nature Structural and Molecular Biology.

HIV-1, like other viruses, lacks the machinery to produce its own proteins and must rely on the host cell to translate its genetic instructions. After entering host cells, it seizes control of the translation process, which converts messenger ribonucleic acid (mRNA) into proteins. “In this study, we combined ribosome profiling, RNA sequencing and RNA structural probing to map the viral and host translational landscape and pausing during replication of the virus in unprecedented detail,” says corresponding author Neva Caliskan.

Cheat Codes of Viral Translation

One of the key findings was the discovery of previously unrecognized elements in HIV-1 RNA called upstream open reading frames (uORFs) and internal open reading frames (iORFs). These “hidden gene fragments” may play a crucial role in fine-tuning the production of viral proteins as well as the interaction with the host immune system. “For instance, uORFs and iORFs can act as regulators, ensuring precise timing and levels of protein synthesis”, explains Anuja Kibe, a postdoctoral researcher at the HIRI and first author of the study.

Another important discovery was an intricate RNA structure near the critical “frameshift site” in the viral genome. This frameshift site is essential for the virus to produce the correct proportions of two key proteins, Gag and Gag-Pol, which are necessary for assembling infectious particles and replication of HIV-1. The researchers demonstrated that this extended RNA fold not only promotes ribosome collisions upstream of the site (a mechanism that appears to regulate translation) but also maintains the frameshifting efficiency. “Our team also showed that targeting this RNA structure with antisense molecules could significantly reduce frameshift efficiency by nearly 40 percent, offering a promising new avenue for antiviral drug development”, reports Caliskan. 

A Game of Priorities

Redmond Smyth, a former Helmholtz Young Investigator Group Leader at the HIRI and currently a group leader at the Centre National de Recherche Scientifique (CNRS) in Strasbourg, France, mentions, “Interestingly, our analysis revealed that, while HIV-1 mRNAs are translated efficiently throughout infection, the virus suppresses the protein production of the host, particularly at the translation initiation stage.” This allows HIV-1 to prioritise its own needs while effectively stalling the host defence mechanisms. Thus, the virus can manipulate the host cell machinery in ways that remain robust even under stress conditions.

More Than Traffic Jams

The researchers also observed that ribosomes collide at specific regions of the viral RNA, particularly upstream of the frameshift site. “These collisions are not accidental but are instead tightly regulated pauses that may influence how ribosomes interact with downstream RNA structures,” says Florian Erhard, study co-author and Chair of Computational Immunology at the University of Regensburg.

Overall, the study provides not only a detailed map of the translational landscape of HIV-1 infected cells but also a wealth of potential targets for therapeutic intervention. The identification of RNA structures and genetic elements critical for viral replication highlights new opportunities for the development of drugs aimed at disrupting these processes. “By understanding how the virus cleverly manipulates our cells, these discoveries will bring us closer to innovative treatments that could one day turn tables and outsmart the virus itself,” Caliskan adds.

Source: Helmholtz Centre for Infection Research

Categories : HIVTags :

#InTheSpotlight | Where are We in the Search for an HIV Cure?

On By ModernMedia

By Elri Voigt

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.

YouTube video

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”.

Republished from Spotlight under a Creative Commons licence.

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Categories : HIVTags :

Sub-Saharan Africa Leads Global HIV Decline

On By ModernMedia
Photo by Sergey Mikheev on Unsplash

The Institute for Health Metrics and Evaluation (IHME) has published a new study in The Lancet HIV journal that revealed significant progress in the global fight against HIV/AIDS, alongside a stark warning that current trends indicate the world is not on track to meet the ambitious UNAIDS 2030 targets.

The research, which analysed the global, regional, and national burden of HIV/AIDS among 204 countries and territories from 1990 to 2021 and forecasted trends to 2050, highlighted a mixed landscape of achievements and challenges in the battle against this global epidemic.

Between 2010 and 2021, new HIV infections decreased from 2.1 million to 1.7 million, and HIV-related deaths decreased from 1.2 million to 718 000. Despite this progress, researchers found regional variation in the HIV response and forecast the world is not on track to meet UNAIDS 2030 targets to cut new HIV infections and AIDS-related deaths by 90%.

Sub-Saharan Africa leads the world in cutting new HIV infections and deaths from the disease

The global decline in HIV incidence is largely driven by sub-Saharan Africa, where the likelihood of getting HIV over a lifetime has fallen by 60% since its peak in 1995. This region also achieved the largest decrease in population without a suppressed level of HIV (PUV), from 19.7 million people in 2003 to 11.3 million people in 2021.

In contrast, the lifetime probability of HIV acquisition increased from 0.4% to 2.8% between 1995 and 2021, while PUV rose from 310 000 people to 680 000 people between 2003 and 2021 in Central Europe, Eastern Europe, and Central Asia.

“The world has made remarkable global progress to significantly reduce the number of new HIV infections and lives lost to the disease, yet there are remaining challenges to overcome,” said Dr. Hmwe Kyu, IHME Associate Professor and study author. “More than a million people acquire a new HIV infection each year and, of the 40 million people living with HIV, a quarter are not receiving treatment,” she added.

Despite progress, UNAIDS’s HIV infection reduction and AIDS-related deaths 2030 targets won’t be met

Although substantial progress has been made against HIV incidence and AIDS-related mortality, the world is not on target to meet the UN’s 2030 targets to reduce new HIV infections and AIDS-related deaths by 90%.

The number of people living with HIV is expected to peak at 44.4 million by 2039, followed by a gradual decrease to 43.4 million people by 2050.

“The global community must make sustained and substantive efforts to sharpen the focus on prevention, optimize access to antiretroviral therapy, and make HIV testing widely available to achieve prompt diagnosis and linkage to care,” said Dr. Kyu.

New cases of HIV, and deaths associated with the disease, are expected to continue to decrease globally. However, long-term increases have been forecast in North Africa and the Middle East, where only 67% of people living with HIV are aware of their status, 50% access ART, and 45% are virally suppressed.

“Although new HIV infections and HIV-related mortality have fallen globally, they are increasing in several nations and regions. Our analysis is designed to inform countries’ sustained response to HIV that includes expanded access to lifesaving antiretroviral therapy (ART), effective prevention options, and innovative care models,” said Austin Carter, IHME Research Scientist.

The study authors set a series of recommendations to sustain and invigorate the global HIV response, including the strengthening of the US President’s Emergency Plan for AIDS Relief (PEPFAR) and other similar public health programs dedicated to HIV control, as well as the expansion of prevention services, with a multitude of existing and emerging technologies. Additionally, interventions and care delivery models that work must be studied and implemented effectively and equitably, with special emphasis on measuring progress and addressing remaining gaps in our collective goal of ending the HIV epidemic.

The findings and recommendations from the new study by the GBD 2021 HIV collaborators serve as a call to action for governments, health care providers, and the global community to renew their commitment to ending the HIV epidemic. Only through sustained, comprehensive, and equitable efforts will the world be able to achieve the UNAIDS 2030 targets and ultimately eradicate HIV/AIDS as a public health threat.

Source: Institute for Health Metrics and Evaluation

Categories : HIVTags :

Trial Shows Twice-yearly Injection to be 99% Effective in HIV Prevention

On By ModernMedia
Photo by Miguel Á. Padriñán: https://www.pexels.com/photo/syringe-and-pills-on-blue-background-3936368/

For oral medications that prevent new HIV infection to be effective, the patient must take certain actions, including attending doctor’s visits every three months and – most importantly – consistency.

These daily oral antiretrovirals, more commonly referred to as PrEP (pre-exposure prophylaxis), such as Truvada®, are extremely effective at HIV prevention, but only if they are taken daily as directed. Truvada’s efficacy is greatly compromised when taken inconsistently.

However, results from a recent Gilead-funded clinical trial (Purpose-2) led by physicians at Emory University and Grady Health System indicate that a twice-yearly injection of Lenacapavir offers a 96% reduced risk of infection overall, making the injection significantly more effective than the daily oral PrEP. The findings were recently published in the New England Journal of Medicine.

“Seeing these high levels of efficacy – at almost 100% – in an injectable that people only have to take every six months is incredible,” says Colleen Kelley, MD, lead author of the study and professor in the School of Medicine at Emory University. “This is a considerable and profound advancement in medicine, especially for people whose circumstances don’t allow them to take a daily oral medication, and for those among populations disproportionately impacted by HIV.”  

In the randomised, double-blind, Phase III clinical trial comparing the efficacy of the two medications, 99% of the participants in the Lenacapavir group did not acquire an HIV infection. During the trial, only two participants in the Lenacapavir group, comprised of 2,179 people, acquired HIV. This compares to nine new HIV infections in the Truvada®group, which had 1,086 people. The trial showed that adherence to the injectable was higher than of the daily oral pill. 

Kelley adds that while PrEP is incredibly effective at preventing infection, part of what made the injection more effective in the clinical trial was the challenges associated with adherence to a daily oral pill.

“What we see over time is that about half of people who start taking daily oral PrEP stop within a year due to various factors,” says Kelley, referencing healthcare disparities in general. “Having an effective injectable that is only needed twice annually is very significant for people who have trouble accessing healthcare or staying adherent to daily, oral pills.”

The inclusion of racially, ethnically, and gender-diverse participants in the clinical trial was notable because it was representative of populations disproportionately impacted by HIV in real time. For example, the trial groups were comprised of cisgender men and gender-diverse people at 88 sites in Peru, Brazil, Argentina, Mexico, South Africa, Thailand, and the US.

According to the study, the same populations that are disproportionately impacted by HIV are the same populations that have limited access to PrEP – or may have difficulty consistently taking the oral antiretroviral medication – ultimately highlighting the need for more options. The study also indicates that more than half of the new HIV infections nationwide in 2022 were among cisgender gay men, and 70% of those were among Black or Hispanic individuals. 

Valeria Cantos, MD, associate professor in the School of Medicine at Emory University, physician at Grady Memorial Hospital, and the principal investigator for the clinical trial at the Grady research site, emphasized the importance of having trials that include populations truly representative of the patients that Grady serves.

“At Grady, our focus is on increased representation of underserved and vulnerable populations, acknowledging and addressing the distrust towards research held by some community members due to prior abuses or neglect of these populations by research institutions in the past,” Cantos says. “Grady is an established, trusted research site because of its commitment to equity.”

 At the Grady clinical trial site, medical materials were available in Spanish, and bilingual staff members recruited and enrolled trial participants who only spoke Spanish. Cantos also indicated that the site enrolled participants who are representative of the populations that would benefit the most from Lenacapavir. In addition to Grady, the Hope Clinic and Emory Midtown Hospital were among the 88 sites supporting the clinical trial. 

“We are not reaching everyone we need to reach with our current HIV prevention interventions, such as those who are disproportionately impacted by HIV and health care disparities,” says Kelley. “For people that are unable to take the daily oral pills, the injectable agents can really give incredible efficacy and be a game changer in helping them stay HIV negative.”

Since the Phase III clinical trial has been completed and submitted by the FDA for consideration, Kelley is hopeful that Lenacapavir may be approved by 2025 for commercial use.

Source: Emory Health Sciences

Categories : HIV PaediatricsTags :

Iron Supplements for Children with HIV may Aid Brain Development

On By ModernMedia
Photo by Miguel Á. Padriñán

A University of Minnesota Medical School research team has found that giving iron supplements to children living with human immunodeficiency virus (HIV) in sub-Saharan Africa could be an important first step in optimising brain development. 

The study, published in Lancet HIV, demonstrates that iron, while often withheld from children with HIV due to fear of increasing infection risk, is in fact beneficial. This finding paves the way for future research examining iron’s role in neurodevelopmental outcomes in children with HIV. 

“With the success and widespread availability of antiretroviral therapy (ART), children with HIV in sub-Saharan Africa are living longer, and optimising their brain development is a new public health imperative,” said Sarah Cusick, PhD, associate professor at the U of M Medical School and a member of the Masonic Institute for the Developing Brain.

Between May 2018 and November 2019, researchers enrolled 200 children with HIV and anaemia who had received ART for at least six months. The study participants were randomly chosen to receive either iron supplements or a placebo for three months. Children who received iron had higher haemoglobin concentrations and better markers of iron nutrition than those who received the placebo. There also was no evidence of increased risk of infection. 

According to Dr Cusick, further research is needed to assess brain development and infection risk over a longer period of time.

Source: University of Minnesota Medical School