By Fatima Hassan, Leena Menghaney, and Bellinda Nkoana
A new HIV prevention jab has the potential to bring an end to the AIDS epidemic. But a lack of ambition and unjustifiable secrecy over pricing is holding it back, argue three leading health activists.
Imagine a new HIV prevention tool existed that could – if it reached the right people – flick the switch to prevent almost all new HIV cases across the world. You would expect every health system and government to be doing all they can to roll it out to everyone as quickly as possible, regardless of the challenges, right?
The good news is that this scenario is not merely in our imagination because we actually have that tool today. The bad news? The rollout of this breakthrough HIV prevention jab is moving at a glacial pace.
Lenacapavir, a twice-yearly antiretroviral-containing injection, is one of the most promising tools yet in the fight to end AIDS. Data from two major trials released last year showed it offers near-complete protection against HIV infection for some of the most vulnerable groups: young women, men who have sex with men, sex workers, and transgender and gender-diverse people. Trials that test the effectiveness of the jab as prevention in people who inject drugs are also underway. For communities still bearing the brunt of new infections, it could be a game-changer.
Take South Africa as a case in point. Modelling studies suggest the impact could be transformative. If two to four million HIV-negative people here used lenacapavir annually over the next eight years, new infections could dramatically fall, with rates low enough that experts would consider it significant enough to end AIDS.
And yet, the current rollout targets look worryingly timid, particularly for vulnerable communities.
According to the National Department of Health, South Africa’s projected initial target for the first two years of the roll out (April 2026 – March 2028 and subject to registration or interim approval by the South African Health Products Regulatory Authority) of just under 500 000 people, includes the general population and certain vulnerable or key risk population groups – for the latter, the targets are woefully low: 69 799 sex workers, 37 857 transgender people, and 155 946 gay, bisexual, and other men who have sex with men.
This barely scratches the surface of the actual need in vulnerable populations. At this rate, access will be severely rationed, and the epidemic will continue to outpace us.
One reason the roll out cannot be on a mass scale, is not just due to an absent political will, but also because the company that holds the patent, Gilead Sciences, is rationing access. And until a sufficient number of generics come on to the market, voluntarily or through compulsory measures, Gilead will call the shots.
The Trump administration’s funding cuts earlier this year left ambitious plans to roll out lenacapavir in several countries in the Global South in the dust. In response, South Africa, in consultation with the Global Fund for AIDS, Tuberculosis, and Malaria (Global Fund) and indirectly with Gilead, announced plans to repurpose R520-million from an existing Global Fund grant to buy lenacapavir for HIV prevention.
But despite South Africa being asked by the Global Fund to budget $30 per dose ($60, roughly R1 050, per person per year) as its contribution, no one knows the total price the Global Fund is paying Gilead.
Such pricing secrecy is unacceptable, especially when health ministries in low- and middle-income countries are already squeezed by the massive US government funding cuts and debt crises.
Countries excluded from the Global Fund’s supply agreement and Gilead’s inadequate mechanisms for allowing generic competition (they exclude several countries and only a few companies were licensed) will be left to negotiate directly with Gilead, facing the prospect of unaffordable “tiered” prices designed to maximise profit – eerily similar to the COVID vaccine inequitable access debacle. Millions who need HIV prevention could face rationing, with health providers forced to leave the most vulnerable populations behind.
The Global Fund’s willing decision to shield Gilead’s pricing from public disclosure undermines accountability and risks reversing years of hard-won progress towards transparency in medicine pricing in the Global South and elsewhere. This is a dangerous precedent for the global HIV movement as pharmaceutical multinational companies are finding new ways to normalise price secrecy – and the Global Fund has just approved that tactic. While civil society in Global South countries such as South Africa are defending the right to know how public funds are spent, global institutions like the Global Fund in Geneva, are enabling practices that give pharmaceutical corporations a free pass.
The push to normalise secrecy, particularly when public or donor money is involved, should ring alarm bells. If international actors are serious about equitable access, then price transparency must be non-negotiable. Anything less erodes public trust and hands undue power to pharmaceutical companies at the expense of public health. Transparency is also necessary to ensure that the price we pay is fair and justified, because public money should not subsidise Gilead’s profiteering.
All this comes at a time when global health financing is under severe strain. Deep cuts in HIV/AIDS funding have already cost tens of thousands of lives across multiple countries. But rationing prevention is a false economy because the cost of new infections, in lives and long-term treatment, will far outweigh the investment required to scale up prevention now.
As delegates convene this week at the SA AIDS Conference, they must publicly call out the demand for price secrecy from Gilead and the Global Fund for what it is: bullying. It must also raise the funds, domestically and internationally, to pay for lenacapavir for all who need it. Two million people at minimum should be the national target – four times the glacial rollout pace the Global Fund is proposing at present.
The lesson from history is clear: When lifesaving HIV treatment was delayed, millions died needlessly. We cannot afford the same mistake with HIV prevention.
*Hassan, Menghaney, and Nkoana are all part of the global LEN-LA for All Coalition, a grouping that includes the organisations Health GAP, Health Justice Initiative, Sankalp Rehabilitation Trust, Just Tx, and ABIA.
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.
The health department has plans to roll out lenacapavir, a twice-yearly HIV prevention injection, in a select group of public sector clinics by April 2026. Meanwhile, little progress has been made towards rolling out a two-monthly prevention injection, despite the four-year head start this product had on lenacapavir.
Injections that provide months of protection at a time against HIV infection have been hailed by several leading experts as game-changers with the potential to help end the HIV epidemic.
The two antiretroviral-containing injections leading the field are long-acting cabotegravir (CAB-LA) and lenacapavir. Both have been shown to effectively eliminate the risk of contracting HIV in large clinical trials. The main difference between the two shots is that CAB-LA provides two months of protection at a time, while lenacapavir provides six.
CAB-LA captured global attention back in 2020 when pivotal trial results showed that the two-monthly injection was more effective than daily prevention pills in preventing HIV infection. Lenacapavir was thrust into the spotlight four years later in 2024 when two large trials demonstrated that the twice-yearly injection provided almost perfect protection against HIV.
There are still no clear plans for providing CAB-LA in South Africa’s public sector clinics, despite the four-year head start that it had on lenacapavir. By contrast, lenacapavir injections could be available in some select public sector clinics by April of next year, according to reporting by Bhekisisa.
How CAB-LA fell behind
In July 2022, the World Health Organization (WHO) recommended CAB-LA as a tool to prevent HIV and by December 2022 it was registered for use in South Africa.
In February 2023 though, South Africa’s National Essential Medicines Committee stated that it could not recommend the use of CAB-LA in the country because the medicine’s manufacturer, ViiV Healthcare, had yet to share how much it would charge the country for the shots.
It was only in late 2023 that ViiV provided pricing details for public sector procurement in certain low-and middle- income countries, including South Africa. That price was around R540 ($30) per dose or R3 240 ($180) per person per year, which the health department said was unaffordable for the country.
The price has since dropped slightly to around R2 880 ($160) per person per year, Mitchell Warren, from the US-based HIV advocacy organisation AVAC, told Spotlight.
In 2024, the health department requested further details from ViiV on its CAB-LA pricing but there is no indication that any progress has been made towards securing a lower price and enabling local procurement of CAB-LA for public sector facilities.
Khadija Jamaloodien, the top official for health products procurement in the National Department of Health, told Spotlight the department could not comment on whether there have been any developments towards local procurement of CAB-LA.
A spokesperson for ViiV told Spotlight: “We have not received any orders to date for CAB-LA for PrEP to supply to South Africa”. PrEP, or pre-exposure prophylaxis, refers to taking an injection to prevent HIV infection.
What about CAB-LA in the private sector?
For those using private healthcare in South Africa, CAB-LA also remains inaccessible. ViiV has not launched CAB-LA in the private sector or disclosed the price at which it will sell CAB-LA through private pharmacies.
ViiV did not respond to Spotlight’s questions regarding its plans and timelines for launching CAB-LA in the country’s private sector.
PEPFAR steps in, but doesn’t deliver
After the health department balked at ViiV’s CAB-LA price for the public sector, the United States President’s Emergency Plan for AIDS Relief (PEPFAR) announced plans to kick start the rollout of CAB-LA in South Africa and some other African countries.
PEPFAR pledged to buy CAB-LA from ViiV for donation to ten African countries during 2024 and 2025. The largest donation of 231 000 CAB-LA doses was designated for South Africa.
While some of the PEPFAR-donated stock began reaching countries before the Trump administration halted foreign aid on 20 January, according to Warren, South Africa never received any of the promised doses.
These donations are no longer expected, given cuts to the agency’s capacity and budget under the Trump administration.
The US State Department did not respond to Spotlight’s questions seeking confirmation that the CAB-LA donations would no longer be delivered, but our health department told Spotlight it doesn’t expect to receive this donation.
Gilead leapfrogs ViiV
Amid the delays and uncertainty surrounding CAB-LA’s pricing and rollout, Gilead, the company that manufactures lenacapavir, has positioned their product to become the first long-acting injectable form of HIV prevention available at any real scale in South Africa.
While lenacapavir is not yet registered in South Africa, Hasina Subedar, the senior technical advisor for HIV prevention in the National Department of Health, told Bhekisisa that it plans to start rolling out lenacapavir in 300 public clinics by April 2026 – less than 10% of the well over 3000 clinics in the country.
SAHPRA authorisation is expected to be granted in the coming months, as lenacapavir has already been recommended for marketing authorisation through the EU medicines for all (EU-M4All) initiative – a process which includes regulators from South Africa. In addition to securing local registration, lenacapavir must also receive a positive recommendation from South Africa’s National Essential Medicines List Committee to enable its rollout.
Gilead has secured a deal with the Global Fund for HIV, TB and Malaria, as well as private donors, that will allow lenacapavir to be rolled out in eight African countries, including in South Africa at a cost to country of R1080 ($60) per person per year.
Under this deal, private donations from the Children’s Investment Fund Foundation (CIFF) will also contribute toward procurement of lenacapavir. CIFF contributions will be above and beyond the $60 contributed by countries per person per year.
While the amount that Gilead will recoup for a year’s supply of lenacapavir under the deal has not been disclosed, it is speculated to be between R1800 ($100) and R2 160 ($120), according to Warren.
He added that Gilead’s deal with the Global Fund will allow countries to begin budgeting and planning for lenacapavir’s rollout using Gilead’s product while they await availability of more affordable generic products in a few years’ time.
The lack of transparency around Gilead’s pricing is uncommon in South Africa, which has strong legal requirements for medicine price transparency. Despite transparency concerns, the National Department of Health has indicated that they will participate in Gilead’s Global Fund arrangement.
By keeping the price secret, two advocacy groups, the Health Justice Initiative and Health Gap, have argued that the deal will undermine efforts in countries not included in the arrangement to negotiate and secure affordable pricing of lenacapavir.
Are HIV prevention injections cost effective for South Africa?
Local researchers have crunched the numbers to establish whether CAB-LA and lenacapavir offer good value for money.
These analyses compared the cost-effectiveness of HIV injections to the widely available prevention pills in public clinics, Lise Jamieson, senior researcher at WITS HE2RO, told Spotlight
The prevention pills provided by the National Department of Health are purchased for R1000 per person per year, said Jamaloodien.
Jamieson said that, according to modelling, prevention injections will avert more HIV infections than prevention pills. Generally speaking, products that provide protection for longer periods are more effective since their efficacy is less dependent on people regularly taking pills or going to the clinic to get an injection. We can thus accept a higher price for lenacapavir (providing six month of protection) than for CAB-LA (only two months of protection) because modelling indicates that this product will avert more HIV infections and delivers more treatment cost savings over time.
Jamieson said according to the latest iteration of their cost-effectiveness modelling, which has not yet been published, CAB-LA needs to be capped around R1800 ($100) per person per year to be cost effective, while lenacapavir needs to be capped around R3600 ($170) per person per year.
Based on this analysis, for South Africa to roll out lenacapavir at $60 per person per year is highly cost-effective, while buying CAB-LA at $160 per person per year is not cost-effective.
Lenacapavir use also requires fewer clinic visits per year than CAB-LA (two versus six) which places less of a strain on health facilities and providers.
Cheaper generic versions of lenacapavir and CAB-LA are expected to become available in 2027.
Lenacapavir generics, Warren said, are expected to enter the market around the same time as generic CAB-LA despite CAB-LA’s initial head start. This is because Gilead was quicker to license generic manufacturers and used a faster licensing approach than ViiV, he added.
Compared to CAB-LA, Warren said it would be faster to show that the generic version of lenacapavir works the same as the original – a necessary step before generic products can be approved. Added to this, he noted that generic companies would likely move faster to bring lenacapavir to market because buyers showed more interest in it.
How will procurement of lenacapavir be funded?
While lenacapavir is cost effective for South Africa at $60 per person per year, purchasing it may nevertheless be challenging given the country’s tight healthcare budget.
HIV prevention pills are procured domestically in South Africa, but Jamieson said the country will need additional funds or donor support to roll out lenacapavir.
The National Department of Health and the Global Fund agreed to allocate R520 million of the country’s Global Fund grant towards buying lenacapavir, Bhekisisa reported in July. This allocation will allow more than 450 000 people in the country to access lenacapavir over the next three years.
Can lenacapavir turn the tide on the epidemic?
In addition to looking at the cost-effectiveness of long acting injectables, Jamieson and her colleagues have modelled how the rollout of injectable HIV prevention options will impact new HIV infections in the country.
Jamieson said if South Africa initiates roughly 1 million people on lenacapavir over the next year and then increase access to reach 4 million people in the next 20 years, HIV incidence could fall below 0.1% by 2038 – with a projected 3.5 million people on lenacapavir by then. At this level, the country would effectively end the HIV epidemic.
Scaling up lenacapavir to this level will require significant political will and additional investment above and beyond what has already been committed by the Global Fund.
Meanwhile, researchers are working on new versions of lenacapavir and CAB-LA that could double the length of protection offered by each.
As Spotlight previously reported, there are promising signs for a lenacapavir formulation that could provide 12 months of protection as opposed to the current six, and a CAB-LA formulation that could provide four months of protection rather than two. HIV prevention tablets that provide a month of protection at a time are also under development. It however remains to be seen whether these new formulations will succeed in the pivotal clinical trials testing their safety and effectiveness.
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 new study in Nature shows that delivering a single injection of gene therapy at birth may offer years-long protection against HIV, taking advantage of a critical window in early life that could reshape the fight against paediatric infections in high-risk regions.
This study is among the first to show that the first weeks of life, when the immune system is naturally more tolerant, may be the optimal window for delivering gene therapies that would otherwise be rejected at older ages.
“Nearly 300 children are infected with HIV each day,” said first author Amir Ardeshir, associate professor of microbiology and immunology at the Tulane National Primate Research Center, who conducted the study alongside fellow researchers at the California National Primate Research Center. “This approach could help protect newborns in high-risk areas during the most vulnerable period of their lives.”
“This is a one-and-done treatment that fits the critical time when these mothers with HIV in resource-limited areas are most likely to see a doctor.”
Amir Ardeshir
In the study, nonhuman primates received a gene therapy that programs cells to continuously produce HIV-fighting antibodies. Timing proved critical to the one-time treatment offering long-term protection.
Those that received the treatment within their first month of life were protected from infection for at least three years with no need for a booster, potentially signifying coverage into adolescence in humans. In contrast, those treated at 8–12 weeks showed a more developed, less tolerant immune system that did not accept the treatment as effectively.
“This is a one-and-done treatment that fits the critical time when these mothers with HIV in resource-limited areas are most likely to see a doctor,” Ardeshir said. “As long as the treatment is delivered close to birth, the baby’s immune system will accept it and believe it’s part of itself.”
More than 100 000 children acquire HIV annually, primarily through mother-to-child transmission after birth from breastfeeding. Antiretroviral treatments have shown success in suppressing the virus and limiting transmission. However, adherence to treatment and access to doctors both decline after childbirth, particularly in areas with limited access to healthcare.
To deliver the treatment, researchers used an adeno-associated virus (AAV), a harmless virus that can act as a cargo truck to deliver genetic code to cells. The virus was sent to muscle cells, unique in their longevity, and delivered instructions to produce broadly neutralising antibodies, or bNAbs, which are capable of neutralising multiple strains of HIV.
This approach solved a longstanding problem with bNAbs. Previous studies found them effective at fighting HIV, but they required repeated infusions, which are costly and pose logistical challenges in low-resource settings.
“Instead, we turn these muscle cells – which are long-lived – into micro factories that just keep producing these antibodies,” Ardeshir said.
Newborns showed greater tolerance and expressed high levels of bNAbs, which successfully prevented infection, while older infants and juveniles were more likely to have produced anti-drug antibodies that shut down the treatment.
Researchers also found that exposing fetuses to the antibodies before birth helped older infants accept the gene therapy later, avoiding the immune rejection that often occurs with age.
Still, Ardeshir said a one-time injection at birth offered a more cost-effective and feasible real-world solution, while putting less burden on the mother for a follow-up visit.
Questions remain as to how the results translate to human infants and children, who may be less susceptible to AAV-delivered treatments. The study also used one strain of simian–human immunodeficiency virus, which doesn’t reflect the variety of HIV strains.
If successful, however, this treatment could dramatically reduce mother-to-child HIV transmission rates in high-risk regions such as sub-Saharan Africa, where 90% of paediatric HIV cases can be found. It may also be adapted to protect against other infectious diseases like malaria, which disproportionately affects young children in low-income countries.
“Nothing like this was possible to achieve even 10 years ago,” Ardeshir said. “This was a huge result, and now we have all the ingredients to take on HIV.”
The cancellation of PEPFAR funding to South Africa could cause between 150 000 and 295 000 additional HIV infections by the end of 2028. This is unless the South African government covers some of the defunded services.
These are the preliminary findings of a new modelling study commissioned by the National Health Department to look into the impact of PEPFAR funding cuts in South Africa. It was authored by researchers at the University of Cape Town (UCT) and University of the Witwatersrand (WITS). PEPFAR is a multi-billion dollar US initiative that supports HIV-related services globally, but which has been significantly slashed by the Trump administration since February.
The research on South Africa comes at the same time that a separate modelling study was published in The Lancet which found that the discontinuation of PEPFAR could cause an additional 1-million HIV infections among children in sub-Saharan Africa by 2030. This would lead to the deaths of about 500 000 children according to the study, while over 2-million others would be left orphaned.
On 20 January, newly-elected US president Donald Trump issued an executive order which suspended virtually all US foreign development assistance for 90 days pending a review. As a result, US-backed aid programmes were brought to a standstill across the world, including in South Africa. While a waiver was published which supposedly allowed some PEPFAR-related activities to continue, this had a limited effect in practice.
Since then, some US grants have resumed, while others have been cancelled. The value of all terminated grants comes to tens of billions of dollars globally. In South Africa, numerous awards have been cancelled from PEPFAR, which had provided roughly R7.5-billion to non-profit organisations in the country in 2024. These organisations primarily used the money to hire and deploy health workers in government clinics, or to operate independent health facilities. Many of these have now been forced to close.
While there are still some active PEPFAR grants in South Africa, it’s unclear how much longer these will be retained, as many are only approved until September. The new study focusing on South Africa models what would happen if all PEPFAR funding was eliminated.
Up to 65 000 additional deaths expected by 2028
In 2024 roughly 78% of all people who had HIV in South Africa were on antiretroviral (ARV) treatment. This figure has been steadily rising over time. By 2026, it was expected to climb to 81%, according to Dr Lise Jamieson, lead author of the local modelling study.
But this trend will be reversed if the entire PEPFAR programme is cancelled and the government fails to step in. ARV coverage among people with HIV would drop to 70% by 2026, according to the study. Under the model’s more pessimistic scenario, the figure would drop even lower – to 59% by 2026.
This is partly because some people living with HIV in South Africa get their ARVs directly from PEPFAR-funded drop-in centres. If these centres close down, some patients may stop taking their ARVs. Indeed, this is precisely what happened after one centre in Pretoria stopped providing services.
The loss of PEPFAR funds could also hinder the health system’s capacity to get newly-infected people on HIV treatment. For instance, PEPFAR-funded organisations had employed nearly 2000 lay counsellors across South Africa who tested people for HIV. Without these staff, fewer people will be diagnosed and get started on treatment.
Not only will ARV coverage drop due to the cuts, but HIV prevention services will also be affected, according to the study. For instance, PEPFAR-funded drop-in sites had been providing people with pills that prevent HIV, called pre-exposure prophylaxis (PrEP). These services were targeted at groups most likely to contract and transmit HIV, like sex workers. According to the new modelling study, the full termination of PEPFAR would lead to as much as a 55% reduction in PrEP coverage for female sex workers by 2026.
Because of factors like these, the researchers estimate that the PEPFAR cuts would cause between 56 000 and 65 000 additional HIV-related deaths in South Africa by 2028. By 2045, this would increase to between 500 000 and 700 000 deaths.
Nearly 90% of USAID contracts terminated in South Africa
All of these results only hold if the South African government fails to step in, according to Jamieson. The modelling study finds that to cover all PEPFAR services from 2025 to 2028, the government would need to spend an extra R13 to 30-billion in total.
It’s unlikely that the government will cough up this amount, but according to Jamieson the National Health Department is taking steps to identify and support certain key services that were defunded by PEPFAR. She is hopeful that the results may not be as drastic as what the study suggests.
Another caveat is that the modelling study estimated what would happen if South Africa lost all of its PEPFAR funding. But at least for now, there are still some grants reaching beneficiaries in the country.
PEPFAR funds are primarily distributed by two US agencies – the US Agency for International Development (USAID) and the US Centres for Disease Control and Prevention (CDC). While both agencies paused funding after the initial suspension order in late-January, the CDC resumed its funding roughly two weeks later. This was after a US federal court ruled that the Trump administration could not freeze congressionally appropriated funds.
CDC grants only appear to be active until September (at least for South African beneficiaries), though uncertainty remains about this.
USAID has taken a much harder line – funding was suspended from late January. By late-February, the agency moved from pausing funds to issuing termination notices to most of its beneficiaries.
In South Africa, roughly 89% of all USAID funding has been cancelled. The value of all cancelled funds comes to about US$261-million (R5.2-billion). Only five other countries have faced larger cuts in absolute terms (see all country-level estimates here). Spotlight and GroundUp have confirmed that at least some of the remaining 11% of USAID funding has once again begun flowing to beneficiaries in the country.
Thus, a small amount of USAID funding is trickling into South Africa, while CDC funds have largely been retained in full. Though it’s unclear for how much longer.
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.
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.
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
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.
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.
In June, we heard what could be this year’s biggest HIV breakthrough: a twice-yearly injection can prevent HIV infection. Findings from a second large study of the jab has now confirmed that it works. Elri Voigt goes over the new findings and unpacks the licenses that are expected to facilitate the availability of generic versions of the jab in over a hundred countries, including South Africa.
The second of two pivotal studies of a six-monthly HIV prevention injection containing the antiretroviral drug lenacapavir has confirmed that the jab works remarkably well.
The first study, called PURPOSE 1, found that the jab is safe and highly effective at preventing HIV infection in women. The second, called PURPOSE 2, found the same for cisgender men, transgender men, transgender women and non-binary people who have sex with men assigned male at birth.
Interim findings from PURPOSE 2 were presented last week at the HIV Research for Prevention (HIVR4P) conference in Lima, Peru.
The researchers compared the safety and efficacy of lenacapavir injections every six months to a daily HIV prevention pill – a combination of emtricitabine and tenofovir disoproxil fumarate, called F/TDF. The results have not yet been published in a peer reviewed journal, but is expected to be soon, according to Principal Investigator for PURPOSE 2 Dr Colleen Kelley, a professor of medicine at Emory University’s School of Medicine.
In the PURPOSE 1 study, none of the 2 134 people receiving the lenacapavir injection got HIV during the study. In PURPOSE 2, there were two HIV infections among the 2 179 people receiving the injection. These numbers are dramatically better than those for HIV prevention pills and for people in the communities where the study was done who were not receiving prevention injections or pills.
These findings mean the evidence is now in place for the manufacturer, Gilead Sciences, to file with regulatory authorities to register lenacapavir injections for HIV prevention. Such registration is required before the jab can be marketed for prevention. Lenacapavir injections are already registered in some countries as a last resort treatment for HIV, but not yet in South Africa.
“Now that we have a comprehensive dataset across multiple study populations, Gilead will work urgently with regulatory, government, public health and community partners to ensure that, if approved, we can deliver twice-yearly lenacapavir for PrEP worldwide, for all those who want or need PrEP,” Daniel O’Day, the chairperson and Chief Executive Officer of Gilead said in a press release. (PrEP, or pre-exposure prophylaxis, refers to taking antiretrovirals to prevent HIV infection.)
Top line findings
The interim results presented at HIVR4P by Kelley, showed that when compared to the background HIV incidence calculated in the study, lenacapavir reduced HIV infections by 96%. And when compared to the F/TDF prevention pill, the injection reduced HIV infections by 89%.
Among the 3 265 participants enrolled in the study, 11 people acquired HIV- two of the 2 179 people who were assigned to the lenacapavir arm and nine of the 1 086 participants assigned to the prevention pill arm. This translated to HIV incidence of 0.93 per 100 person years in the prevention pill arm compared to only 0.1 per 100 person years in the lenacapavir arm.
This was compared to the background incidence, which was determined when screening eligible participants for HIV. Out of 4 634 people screened for the study, 378 or 8.2% were diagnosed with HIV. Based on further laboratory testing, it was estimated that of those 378 people, 45 or 11.9% recently acquired HIV (classified as being within the last 120 days or so). This latter group provided the background HIV incidence, which was estimated to be 2.37 per 100 person years.
This is a novel study design, Kelley told Spotlight, because this calculation was used to estimate the HIV incidence that would have occurred in a placebo group without actually enrolling a placebo group.
“It’s no longer ethical to have a placebo group in HIV PrEP trials because we know that we have effective PrEP agents,” she said. “Yet, it’s almost essential to have a placebo group when you design a clinical trial so that you can really say how effective your medication, your new agent is [compared] to having nothing.”
When asked at a press conference about the two breakthrough infections in the lenacapavir arm, Kelley said the analysis for this is ongoing and will hopefully be available at a future conference and in a journal soon. She said that the two breakthrough infections in the lenacapavir arm were detected by routine testing during the study.
Principal Investigator for PURPOSE 2 Professor Colleen Kelley at the 5th HIV Research for Prevention Conference in Lima, Peru. (Photo: Nicole Bergman/IAS)
Kelley added that around 90% of participants in the two study arms were able to receive their injection on time. “So, we at least know that the injections were delivered in a timely fashion for almost all participants,” she said.
Whether or not the two infections occurred in people who had received the jabs on time and according to the study protocol will be closely watched as more study details is shared in the coming months.
To be enrolled in the study, participants had to meet several criteria. They had to be older than 16, never received HIV prevention injections before, weigh more than 35kg, have good kidney function, not have been tested for HIV in the last 12 weeks, and had to have been sexually active in the last 12 months.
All study participants were given a pill a day and an injection, those in the lenacapavir arm received two 1.5 ml lenacapavir injections every six months and a daily placebo pill, while those in the prevention pill arm received the daily F/TDF pill and a placebo injection every six months.
The study was conducted across seven countries, with 6 sites located in South Africa and others in Argentina, Brazil, Mexico, Peru, Thailand, and the United States, according to study data on Gilead’s website.
Safety data
Overall, Kelley said lenacapavir was safe and well-tolerated despite some side effects, mainly related to the injections. A total of 43 people dropped out of the study due to side effects.
The most common adverse event in the study was injection site reactions. There were more injection site reactions in the lenacapavir arm compared to the prevention pill arm. 29 people dropped out of the study because of these, 26 in the lenacapavir arm and 3 in the prevention pill arm (people in this study arm received placebo jabs).
The most common injection site reaction were subcutaneous nodules – these are harmless, usually invisible, small lumps under the skin. Nodules occur because lenacapavir is injected under the skin where it forms a drug depot. Injection site reactions and nodule size decreased with subsequent injections. This side effect and trend of decreasing reactions was also noted in the PURPOSE 1 study. Other injection site reactions were pain and erythema which is a type of skin rash.
According to Kelley, there were no serious adverse events related to injection site reactions.
When injection site reactions are excluded, according to Kelley, the other adverse events were similar across both arms, with 74% of participants in each arm experiencing an adverse event. The majority were mild or moderate.
Seven participants in each study arm dropped out due to side effects that weren’t related to injection site reactions. Those who discontinued from the lenacapavir arm will be given prevention pills for a year. This is done to protect these participants, Kelley explained, from potentially acquiring HIV when lenacapavir levels wane, as well as to reduce the risk of potential drug resistance developing.
There were a few serious adverse events, although Kelley told Spotlight she does not currently have any additional information on what these were. She explained that a serious adverse event is generally classified as something like hospitalisation, a life-threatening condition, an important medical event or adverse pregnancy outcome.
“Usually when we look at something like this, we look at the rates compared in the two arms of the study and it was 3% in the LEN [lenacapavir] arm and 4% in the F/TDF arm, so they were equal, essentially the same in both study arms,” Kelly said.
There were six deaths during the study, but none were related to the study drugs.
Next steps for lenacapavir
Now that the interim results have been announced, both studies have been unblinded and entered an open-label phase where participants have the choice of switching to or continuing with the injection.
Professor Linda-Gail Bekker, the Chief Executive Officer at the Desmond Tutu Health Foundation, recently said on a webinar hosted by the South African Health Technologies Advocacy Coalition, that study participants are now able to use the PrEP option they’d prefer – either oral PrEP or the injection. This means all participants will be able to access lenacapavir through the studies if they wanted to use it.
But it will likely be a while before anyone outside of these studies can access lenacapavir as HIV prevention.
“This is an incredible intervention. Now we have to make sure everyone can get it and that’s going to be the most important next step, ensuring that everyone who needs this drug has access,” Kelley told Spotlight.
Gilead’s generic licensing agreement and pricing
What we do know so far about the next steps for lenacapavir is that the process to allow for generic manufacturing has started. This month, Gilead released its voluntary licensing agreements with six generic companies for manufacturing cheaper versions of lenacapavir.
Dr Andrew Gray, a senior lecturer in Pharmacology at the University of KwaZulu-Natal, told Spotlight that no South African firms have been included in the voluntary licenses – four of the generic licensees are in India, one is in Pakistan, and one is in Egypt.
“In essence, they [the generic companies] are allowed to sell their generic versions in a number of identified countries, specified by Gilead,” Gray said. The agreement lists 120 countries, including South Africa.
Gilead itself will also be prioritising the registration of lenacapavir in 18 countries, which it said represent about 70% of the HIV burden in the countries named in the license. The list includes South Africa, Uganda, and Botswana. Gilead says it will start filing for registration with regulatory authorities by the end of the year.
It will be important to see how quickly Gilead seeks regulatory approval for lenacapavir with the South African Health Products Regulatory Authority (SAHPRA), Gray said. Registration with SAHPRA will be required before the injection can be rolled out in South Africa.
In putting together this timeline, we’ve spoken to several well-placed experts, but we stress that this is very much a back-of-the-envelope exercise and far from set in stone. (Infograph: Spotlight)
Some countries won’t be able to procure generics
Gilead received criticism for several omissions from the list of countries that the generic manufacturers can sell to. The US-based HIV advocacy group AIDS Vaccine Advocacy Coalition, among others, pointed out the exclusion of several countries which have high HIV incidence. Some of those countries participated in PURPOSE 2- namely Brazil, Argentina, Mexico and Peru.
A spokesperson from Gilead told Spotlight the manufacturer’s access policy included tailored approaches to ensure rapid and broad access of lenacapavir and it objectively considered the countries where a voluntary licence would provide the most benefit.
“Gilead’s voluntary licence primarily covers countries based on economic need and HIV burden, which are primarily low- and lower-middle income countries. The voluntary licence also covers certain middle-income countries with limited access to healthcare,” the spokesperson said.
Acknowledging that some middle-income countries do have a high HIV burden, Gilead is “exploring several innovative strategies to support access to LEN for PrEP (if approved), including tiered pricing, and are working with payors to establish fast, efficient pathways to help reach people who need or want PrEP”, said the spokesperson.
“Ensuring access in middle-income and upper-middle income countries, including those in Latin America, is a priority for Gilead. Planning for these countries, incorporating input from advocates and global health organizations, is ongoing and updates will be shared as discussions progress,” the spokesperson added. “Additionally, Gilead is committed to ensuring that individuals who participated in the PURPOSE studies have been offered and will be able to stay on open label lenacapavir until it is available in their country.”
The company’s decision to license generic manufacturers directly is at odds with earlier calls from several activist groups and UNAIDS to license via the UN-backed Medicines Patent Pool.
Pricing
It will also be important to see if Gilead will disclose a single exit price for the South African market, according to Gray.
In its press release announcing the voluntary licensing agreement, Gilead stated it will “support low-cost access to the drug in high-incidence, resource-limited countries through a two-part strategy: establishing a robust voluntary licensing program and planning to provide Gilead-supplied product at no profit to Gilead until generic manufacturers are able to fully support demand”.
It is too early in the process to reveal a price for lenacapavir yet, the spokesperson from Gilead told Spotlight.
“While Gilead prepares for global regulatory filings, it is too early to disclose the price of lenacapavir for HIV prevention. Our pledge is to price our medicines to reflect the value they deliver to people, patients, healthcare systems and society. For Gilead-branded lenacapavir, we do plan to price it at no profit to Gilead in 18 select high-incidence, resource-limited countries until generic manufacturers are able to fully support demand,” the spokesperson said.
Spotlight previously reported on research that estimated that if produced at sufficient volumes, the price of lenacapavir could be drastically reduced to levels likely considered affordable by the South African government. For instance, if enough volume was produced to supply 10 million people with PrEP, the price for the injection could be as low as $40 (under R800) per person per year. At the moment, Gilead supplies lenacapavir for HIV treatment in wealthy countries for about $40 000 per person per year.
Gilead’s lenacapavir product will be the first to register in South Africa and will almost certainly be the only lenacapavir product available here for several years – that is because it is expected to take generic manufacturers a few years before they can start producing generic lenacapavir. Based on calculations made for other PrEP products, it seems unlikely that the Department of Health would be willing to procure lenacapavir at a price significantly above R1 000 per person per year. The HIV prevention pill currently costs government around R800 per person per year.
Finalised data published in the New England Journal of Medicine, has confirmed the stunning results of a trial in which a twice-yearly dose of lenacapavir completely prevented HIV infection in a group of adolescent girls and women in South Africa and Uganda.
A major challenge with HIV prophylaxis with cisgender women is adherence and persistence with daily oral regimens. The twice-yearly subcutaneous injection of lenacapavir helps to circumvent these problems by offering extended protection.
Based on the initial results announced by Gilead Sciences on the 20th of June, the PURPOSE 1 phase 3 clinical trial met its key efficacy endpoints of superiority of twice-yearly lenacapavir to once-daily oral (emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF) and background HIV incidence. Given the strength of these results, the blinded phase of the trial was halted and open-label lenacapavir was offered to all participants.
The double-blind, randomised, controlled trial recruited 5338 participants who were initially HIV-negative. They were randomised 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral F/TDF (active control); all participants also received the alternate subcutaneous or oral placebo. They compared the efficacy of lenacapavir and F/TAF with F/TDF against the estimated background incidence of HIV infection.
Among the 2134 participants in the lenacapavir group, there were 0 infections (0 per 100 person-years). Meanwhile in the F/TAF group, there were 39 infections among 2136 participants (2.02 per 100 person-years) and 16 infections among the F/TDF group’s 1068 participants (1.69 per 100 person-years).
HIV incidence with lenacapavir was significantly lower than background HIV incidence and than HIV incidence with F/TDF. HIV incidence with F/TAF did not differ significantly from background HIV incidence, and no evidence of a meaningful difference in HIV incidence was observed between F/TAF and F/TDF.
The researchers did note that adherence to F/TAF and F/TDF was low. While no safety concerns were found, injection-site reactions were more common in the lenacapavir group (68.8%) than in the placebo injection group (F/TAF and F/TDF combined) (34.9%); 4 participants in the lenacapavir group (0.2%) discontinued the trial regimen owing to injection-site reactions.
