South Africa has become the first African country, and our medicines regulator the third worldwide, to register the revolutionary twice-a-year anti-HIV jab lenacapavir (LEN) that could bring an end to HIV/Aids if enough people take it.
In June the US Food and Drug Administration (FDA) registered LEN, which is injected into the fat under someone’s skin once every six months, under the name Yeztugo and the European Medicines Agency (EMA) approved it in July as Yeytuo.
The South African Health Products Regulatory Authority (Sahpra) approved LEN on October 21.
In South Africa the LEN injection has been registered under the name Lenacapavir 464mg solution injection Gilead, Sahpra CEO Boitumelo Semete-Makokotlela told Bhekisisa.
“The registration of lenacapavir is a gamechanger given the high infection rate of HIV in South Africa,” she said in a press release. “The product is the most effective HIV prevention measure thus far.”
Though LEN’s manufacturer, Gilead Sciences, applied to Sahpra for registration in March, the local leg of the registration only started on July 22 after the EU-Medicines for all (EU-M4all) programme, a service the EMA offers to countries including South Africa to help speed up registrations, approved it. A similar process was followed with the Janssen vaccine.
How does LEN work?
HIV needs to replicate to survive, but like other viruses it can’t survive on its own, Linda-Gail Bekker, who heads the Desmond Tutu Health Foundation and was also chief investigator in a trial that tested LEN on teens and young women, explained at a LEN meeting organised by South Africa’s Aids Council (Sanac) earlier this month.
To survive in humans, HIV hijacks a type of immune cell called a CD-4 cell and worms itself into its DNA, forcing the cell to make copies of the virus instead of itself, Bekker said.
LEN is called a capsid inhibitor. A capsid is the shell around the virus’ DNA and lenacapavir messes with it in ways that make it impossible for the virus to infiltrate CD-4 cells and replicate.
Lenacapavir belongs to a class of medicines called antiretroviral drugs (ARVs), the same medication doctors use to treat people who are infected with HIV. However, LEN is not commonly used for treatment, only in cases where standard medicines no longer work to fight HIV, meaning for drug-resistant HIV.
Gilead applied for registration for LEN to be used for HIV prevention in South Africa, not as treatment, Sahpra sai.
When antiretroviral drugs are used in this way, when HIV-negative people take them to stop getting infected with the virus, scientists call it pre-exposure prophylaxis, or PrEP.
For PrEP, someone gets a dose of LEN every six months, Bekker said. However, because the dose is too much (927mg) to fit in one syringe, people get two jabs, each containing 464mg of a solution with LEN (each 1.5ml syringe contains 463.5mg of lenacapavir).
LEN works over time. It releases itself slowly into someone’s body over six months and that’s why they only need a shot twice a year. The amount of drug someone needs to be protected against HIV isn’t enough straight after the first dose.
Along with the first dose (two injections of 464mg) people also need to take four 300mg LEN pills, Bekker said, two on the same day as the injections and two on the day after. That way, there’s enough LEN in their body for full protection by the third day.
The pill, Sahpra said, has been registered in South Africa under the name Lenacapavir 300mg Tablet Gilead.
The second dose of LEN is given six months (24 weeks), or up to 26 weeks, after the first dose and no tablets are needed. If someone turns up for their second dose later than 26 weeks, they need to start all over again and also take the tablets.
The most common side-effects Gilead has registered with Sahpra for LEN as PrEP are “local injection site reactions” (inflammatory reactions such as redness, itching and swelling), a hardened mass or lump known as nodules, and an open sore on the skin, Semete-Makokotlela told Bhekisisa.
What happens now?
South Africa’s initial LEN doses are paid for with $29.2m (R503m) by the Global Fund to fight HIV, TB and Malaria and are enough for 456 360 people to be phased in over two years, not close to the between one and two million doses per year the country would need to end Aids within the next 14 to 18 years, according to a Wits University modelling study.
The Global Fund, which is buying the doses directly from Gilead on behalf of South Africa, has told the country to use part of its three-year grant, which kicked in this month. The fund has also asked the health department to budget $60 (around R 1,033) per year for the treatment of one person per year (or R516.50 per dose), but the price at which Gilead sells LEN to the fund has been kept secret.
The government placed its first order on September 30 and Gilead told Bhekisisa it plans for the country’s first shipment to arrive before the end of the year.
However, before LEN can be rolled out in South Africa, the health department’s essential drug committee needs to approve it, a process which is almost completed, chief director for HIV Gugu Shabangu said at the Sanac meeting.
She said the department has developed draft national guidelines and these are awaiting approval from the national health council.
Shabangu said the health department will stock LEN at 360 facilities in 22 of the 52 health districts from early next year. The 22 districts have high rates of new HIV infections and have performed well with managing prescriptions for a daily HIV prevention pill, which the health department will continue to provide, to give people choices about which type of HIV prevention medicine works best for them.
The government will roll out LEN in three phases, Shabangu said. In the second phase, which will start in April 2027, the health department will start to buy generic LEN, which will become available at around the same time.
At least two generic companies will make LEN available at the same price — $40 (R689.12) a year — as the daily HIV prevention pill, but the four pills people who start on LEN need to take are not included in the price. The tablets will cost about an extra $17 (R293).
At the LEN meeting health minister Aaron Motsoaledi said: “We will be earmarking resources in our medium-term expenditure framework to ensure once generic versions become available or prices drop, we can scale up access without interruption.”
Motsoaledi said the US government has written to the department announcing a grant of R2bn to carry SA until the end of March [for programmes funded through the Centres for Disease Control] It is, however, not yet clear if some of the money could be used for LEN roll-out.
The US government’s Aids fund, Pepfar, revealed in September it will invest in bringing LEN “to recipient countries based on countries’ HIV burden and the strength of the country’s existing infrastructure to distribute and deliver the drug”. President Donald Trump administration has, however, not yet made clear which countries, and if it would fund LEN for all people, or only certain groups, such as pregnant and breastfeeding women.
Can SA make LEN?
How many doses the government would be able to afford once generics are available would depend on how much they cost. Six companies received licences from Gilead to make generics, which experts said will result in competitive prices.
Gilead evaluated three South African-based companies for LEN production in 2024. Pharmacare and Cipla Medpro were two of the companies, according to Glaudina Loots of the department of science and innovation. Aspen Pharmacare’s group senior executive Stavros Nicolaou confirmed to Bhekisisa they were the third company.
All three failed the test, mostly because they couldn’t make the active pharmaceutical ingredient, API, also known as the drug substance which is the ingredient that makes LEN work.
“It’s a complex 28-step process,” Loots explained at the Sanac meeting, and “Gilead is looking for a one-stop shop, but we have other options for them”.
The government and Gilead are in discussions about generic licences for local companies to make LEN, but to import the API. “The department of science, technology and innovation with funders such as the Industrial Development Corporation and Technology Innovation Agency are supporting the building of the necessary infrastructure and human resources needed,” Loots said.
Gilead has not announced a price for the public or private sector in South Africa.
“We are in ongoing discussions with the health department to understand their needs,” Caroline Almeida, Gilead’s director of public affairs, told Bhekisisa.
“We are evaluating private market strategies to expand product availability in South Africa as soon as possible. At this time, we do not have a registered price for lenacapavir for the prevention of HIV.”
This story was produced by the Bhekisisa Centre for Health Journalism. Sign up for the newsletter.
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