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). The drug could bring an end to Aids if enough people take it.
The US Food & Drug Administration registered LEN in June under the name Yeztugo and the European Medicines Agency (EMA) approved it in July as Yeytuo. The drug is injected into the fat under a person’s skin once every six months
The South African Health Products Regulatory Authority (Sahpra) approved LEN on October 21.
In South Africa the injection has been registered under the name “Lenacapavir 464mg solution injection Gilead”, Sahpra CEO Boitumelo Semete-Makokotlela tells Bhekisisa.
“The registration of lenacapavir is a game-changer 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.”
The jab, which the health department could start rolling out as early as February, provides protection for HIV-negative people — who weigh 35kg or more — against getting HIV through sex.
Early data from the Desmond Tutu Health Foundation shows it is safe for pregnant and breastfeeding women, a group with a high chance of contracting the virus. Sahpra has not excluded them from access, but doesn’t explicitly mention this group in the registration document. More data is needed, says Semete-Makokotlela.
Sahpra registered LEN within 65 days — 10 days faster than the 75 days it took the regulator to approve the Johnson & Johnson Covid vaccine from drugmaker Janssen in 2021, which was the jab that was registered the fastest in the country, Sahpra tells Bhekisisa.
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 EU-Medicines for all (EU-M4all), a service offered to countries such as 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 up the Desmond Tutu Health Foundation, and was the chief investigator in a trial that tested LEN on teens and young women, explained at a LEN meeting organised by the South African 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 explained.
LEN is a capsid inhibitor. A capsid is the shell around the virus’s 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 already infected with HIV. But LEN is not commonly used for treatment and is used only in cases where standard medicines no longer work to fight HIV — in other words, drug-resistant HIV.
Gilead applied for registration for LEN to be used only for HIV prevention in South Africa, not as treatment, Sahpra says.
When ARVs are used in this way (when HIV-negative people take them to stop themselves from getting infected with the virus) scientists call it pre-exposure prophylaxis or PrEP.
For PrEP, people get a dose of LEN every six months, Bekker explained. But 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 — releasing itself slowly into a person’s body over six months. This is why people only need a shot twice a year. The amount of drug a person needs to be protected against HIV isn’t enough right after the first dose. Along with the first dose (two injections of 464mg) people also need to take four 300mg LEN pills — 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 says, has been registered in South Africa under the name “Lenacapavir 300mg Tablet Gilead”.
The second dose of LEN is given six months (24 to 26 weeks) after the first dose and no tablets are needed. But if someone turns up for their second dose later than 26 weeks, they need to start over again and take the tablets again too.
The most common side effects Gilead has registered with Sahpra for LEN when used as PrEP are “local injection site reactions” (inflammatory reactions such as redness, itching and swelling), a hardened mass or lump (nodule), and an open sore on the skin, Semete-Makokotlela tells Bhekisisa.
The registration of lenacapavir is a game-changer given the high infection rate of HIV in South Africa
— Boitumelo Semete-Makokotlela
What happens now?
South Africa’s initial LEN doses are paid for with $29.2m (around R520m) by the Global Fund to fight HIV, TB and Malaria. There is only enough for 456,360 people to be phased in over two years — not close to the between one-million and two-million doses per year the country would need to end Aids within 14 to 18 years, according to a modelling Wits 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 current three-year grant, which kicked in this month. The fund has also asked the department to budget $60 (about R1,060) a year for the treatment of one person a year ($30 or R518 a dose), but the price at which Gilead sells LEN to the fund has been kept under wraps.
The government placed its first order on September 30 and Gilead told Bhekisisa it plans for the first shipment to arrive before the end of this year.
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 explained.
She said the department has also developed draft national guidelines and is awaiting approval from the national health council.
Shabangu announced that the health department will stock LEN at 360 facilities in 22 of South Africa’s 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. The health department will continue to provide these to give people choices as to 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 (around R692) a year — as the daily HIV prevention pill. However, the four pills that people who start on LEN need to take are not included in the price. These tablets will cost about an extra $17 (about R293).
At the LEN meeting health minister Aaron Motsoaledi said: “We will be earmarking resources in our medium-term expenditure framework to ensure that once generic versions become available or prices drop, we can scale up access without interruption.”
Motsoaledi said the US government had written to the department announcing a grant of about R2bn to carry South Africa until the end of March for programmes funded through the US Centres for Disease Control & Prevention. It is not yet clear if some of that money could be used for LEN rollout.
Pepfar, the US government’s Aids fund, revealed in September that it will invest in bringing LEN “to recipient countries based on HIV burden and the strength of the country’s existing infrastructure to distribute and deliver the drug”. The Trump administration has not yet made clear which countries these would be, and if it would fund LEN for all people or only certain groups such as pregnant and breastfeeding women.
Can South Africa make LEN?
How many doses the government would be able to afford once generics are available would depend on cost. Six companies received licences from Gilead to make generics, which experts say will result in competitive prices.
Gilead evaluated three South African-based companies for LEN production in 2024 — Pharmacare and Cipla Medpro were two of these, according to Glaudina Loots of the department of science & innovation. Aspen Pharmacare’s group senior executive, Stavros Nicolaou, confirmed to Bhekisisa that 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; 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 South African government and Gilead are in discussions about generic licences for local companies to make LEN, but with imported API or drug substance. “The department of science, technology & innovation, together with funders such as the Industrial Development Corp and the Technology Innovation Agency, are actively supporting the building of the necessary infrastructure and human resources needed,” Loots said.
Gilead has not yet announced a price for either the public or private sector in South Africa.
“We are in ongoing discussions with the South African 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.
