The two-monthly HIV prevention injection, cabotegravir (CAB-LA), was approved more than three years ago but never reached government clinics. Now, as the new and revolutionary lenacapavir (LEN) prepares to launch, the quiet exit of CAB-LA carries lessons about what it takes to turn good science into public health, writes Ida Jooste for Bhekisisa.
LEN, which will be rolled out later this year at 360 government clinics with doses donated by the Global Fund to Fight Aids, TB and Malaria, was registered in South Africa in October. But previously, there was CAB-LA, which was approved for HIV prevention in South Africa more than three years ago and was once expected to reshape HIV prevention.
CAB-LA had earned its moment.
In 2020, large international trials showed the injection, given every two months in the buttocks, prevented far more HIV infections than a daily HIV prevention pill – or oral PrEP. The findings were hailed as charting a new path for HIV, “a real game-changer”.
Four years later, lenacapavir, would report even stronger trial results and ignite an even bigger wave of excitement, because it is almost foolproof. The journal Science dubbed it the 2024 breakthrough of the year.
Lenacapavir is injected under the skin, usually in the belly area, just twice a year.
CAB-LA proved that long-acting HIV prevention works. But getting medicine into clinics takes more than good science; it also depends on price, planning and timing. In CAB-LA’s case, those didn’t line up. Modelling studies show it would cost about four times more per person to protect someone with CAB-LA than with generic lenacapavir.
When lenacapavir launches, it will do so with a lower price, donor support already lined up, and plans in place to deliver it.
From promise to pause
For a brief moment in late 2024, South Africa looked poised to launch one of the world’s first public CAB-LA programmes.
At the International Aids Conference in Munich, the US President’s Emergency Plan for Aids Relief (Pepfar) announced it would donate CAB-LA to several African countries, with South Africa due to receive the largest share. The move signalled a move from pilot projects into government clinics.
But the announcement did not turn into orders. As funding uncertainty under Donald Trump’s presidency of the US grew, no national tender followed.
“There were very big plans for cabotegravir in 2025,” said Mitchell Warren, executive director of the HIV advocacy organisation Avac.
“But the South African Government missed a beat and by the time orders were meant to have been placed and product shipped, it got caught up in the 20 January stop-work orders of the US Government. It means we lost a whole year and more with long-acting injectables in South Africa. That means there were infections that could have been averted.”
A smaller initiative continued through Project PrEP, a Unitaid-supported programme in selected government clinics led by Saiqa Mullick, director of implementation science at Wits RHI.
It offered CAB-LA in routine services and has become a real-world test of how injectable PrEP would work in everyday clinic care – who chose it, who switched and who came back for their next dose.
“We’ve seen a preference for injectable PrEP over the daily pills,” said Mullick. “When these studies started, there was every expectation that people who switched from daily pills to CAB-LA would stay on the injection once it became part of routine services.”
Instead, the national roll-out never materialised. CAB-LA was not formally withdrawn. It stalled.
Approved, but stuck
In South Africa, regulatory approval is only the first step. The South African Health Products Regulatory Authority (SAHPRA) registered CAB-LA for HIV prevention in December 2022.
But a different body, the National Essential Medicines List Committee, decides whether approved medicines are added to national guidelines and paid for by the state. CAB-LA was not added, mainly because of its price.
When the US signalled it would donate CAB-LA, preparations began in anticipation of the shipment. “That work was conducted in late 2024,” said pharmacologist Andy Gray of the University of KwaZulu-Natal, who serves as expert on both SAHPRA and the essential medicines committee.
“However, no donated stock was ever delivered. The focus is now entirely on LEN.”
CAB-LA was approved and reviewed, but never procured for government clinics. Without a registered private-sector price, it also never became available to people on medical schemes, or others who would be prepared to pay out of pocket.
The budget reality
But even before the US donation fell through, price was already a problem. With lenacapavir entering the picture at a much lower cost, that problem is becoming harder to ignore.
A South African modelling study compared both injections with the daily HIV prevention pill, and found lenacapavir delivers much better value for money.
CAB-LA would cost about $180 per person per year, while introductory generic versions of LEN are estimated at $40 a year plus an extra first dose that helps the medicine to start working for $17.
To kickstart the rollout in 2026 and 2027, the Global Fund has negotiated a subsidised $60 price per year per patient with lenacapavir’s maker, Gilead Sciences, to provide enough medicine to cover 500 000 people over two years (the $60 per patient per year is the amount countries pay from their Global Fund grants; the subsidised amount is an unknown amount the Fund pays directly to Gilead Sciences to cover the difference between the $60 and the actual price that the Fund negotiated with Gilead, which hasn’t been made public).
If global demand increases significantly, production estimates suggest the generic price could fall even further.
Part of the reason CAB-LA costs more is that it is harder to manufacture. CAB-LA is formulated as a long-acting nano suspension, a complex injectable that is not easy to copy or manufacture widely in large quantities.
Lenacapavir is simpler to produce, making it easier for other companies to manufacture generic versions once licensing allows. When more than one company can make the same medicine, prices usually fall.
As early as November 2023, the Health Department had indicated CAB-LA was too expensive.
“For CAB-LA to be cost effective to the South African Government, the price would need to be within a reasonable range of oral PrEP (the daily pill), which is R129 for a two-month supply. We can’t afford to pay double or thrice the price,” the National Health Department’s chief director of procurement, Khadija Jamaloodien, told Bhekisisa at the time.
The department’s deputy DG for HIV, Fikile Ndlovu, said the assessment has not changed. “Ideally we would offer multiple options, but we have to work within our budget.”
Asked whether it would expand support for CAB-LA in South Africa, the Global Fund told Bhekisisa it funds the injection where countries include it in their plans.
Wider roll-out depends on price and national priorities. ViiV Healthcare, the pharmaceutical company that manufactures the drug, told Bhekisisa supply is available, but no public-sector orders have been placed at current prices.
What CAB-LA showed
Lost in the funding battles was a simple fact: the science was strong.
In the HPTN 084 trial of more than 3 000 women in African countries with high HIV rates, 36 participants taking the daily pill got HIV, compared with four who received the two-monthly injection – the researchers found about nine infections in the pill group for every one in the injection group.
In the previous HPTN 083 trial of just more than 4 500 men who have sex with men and transgender women across three continents, 39 people in the pill group got HIV, compared with 13 in the CAB-LA injection group – roughly three to one.
South Africa helped generate that evidence. And when participants were later given a choice, many chose the injection.
The preference for the injection became clear in the PrEPared to Choose (PtC) study under the leadership of Linda-Gail Bekker, CEO of the Desmond Tutu Health Foundation, which focused on a young population.
“When we offered choice with oral, ring and injectable CAB, 75% of the population went with CAB,” she says. “There was huge excitement around the two-monthly intramuscular injection.”
The pattern was similar in Project PrEP, led by Mullick at Wits RHI, which offered CAB-LA through day-to-day services in selected government clinics. It showed that two-thirds of people who were not already using HIV prevention chose the injectable over daily pills.
Nearly half of those taking the daily pill switched to CAB-LA. Over six months, fewer people using the injection stopped and restarted compared with those on oral PrEP.
But the programme also exposed a gap.
“Prevention use is not linear,” says Mullick, and tracking uptake and adherence for PrEP is different from doing it for lifelong treatment. She said South African HIV data systems were built to track treatment, not prevention where people’s needs may change. “People move in and out of risk. Our systems are still learning how to accommodate that.
“You don’t have to be on PrEP forever. That’s the whole point,” she added.
Since people are not at risk of HIV infection for life, the monitoring of prevention programmes would need to evolve to accommodate this reality.
Without good real-world data – who starts, stops or comes back – it’s hard to predict demand. As Mullick explained, CAB-LA worked as a stress test, showing how injectable PrEP fits into everyday clinics and where systems fall short. That learning should now shape how South Africa plans for the next injection.
“Cabotegravir was the front end of our learning about long-acting injectables,” said Warren of Avac. “People have been trained. Systems have been set up … It was an investment. It wasn’t a waste.”
And while South Africa begins a small-scale roll-out of lenacapavir, Zambia is already learning how to manage more than one type of injection for HIV prevention.
The country, the second in the world to hand out CAB-LA as part of day-to-day government health services, plans to keep the popular first jab in stock while rolling out lenacapavir alongside it.
Zambia’s national plan makes the two anti-HIV shots available along other ways to prevent HIV infection such as the daily HIV prevention pill and condoms.
To help people choose the method that will work best for them, the Health Ministry has developed easy-to-understand pamphlets noting that the roll-out of lenacapavir draws on what they learned worked – and didn’t – when introducing CAB-LA.
This creates a rare chance to see how people choose when both are available.
“They will be able to tell us how people select either CAB or LEN,” said Bekker.
Long-acting injections like LEN can make life easier for patients, with just two shots a year instead of six, and take pressure off clinics. But fewer visits also mean fewer chances to check in on people’s health.
Still, lenacapavir enters with three powerful pluses: it’s cheaper, easier to deliver and offers near-foolproof protection. That’s a rare combination in HIV prevention.
See more from MedicalBrief archives:
Health Department slams cost of anti-HIV CAB-LA shot
Lenacapavir to be rolled out via Pepfar to selected countries
Start planning cabotegravir injection rollout, say SA experts
Fear of side-effects the greatest barrier to long-acting injectable PrEP
New injectable HIV drug could be much cheaper, study shows