South Africa has achieved a historic milestone in HIV prevention by becoming the first African country to approve lenacapavir, a revolutionary twice-yearly injection that could transform the fight against HIV/AIDS. The South African Health Products Regulatory Authority (SAHPRA) announced the approval on Monday, making it the third regulatory authority worldwide—after the US FDA and European Medicines Agency—to authorize the groundbreaking treatment.
Regulatory Breakthrough and Scientific Significance
SAHPRA approved lenacapavir under the name "Lenacapavir 464mg Solution Injection Gilead" following an accelerated review process that took just eight months from application to approval. This represents an unusually fast turnaround, as regulatory approval typically takes well over a year.
"The registration of Lenacapavir is a game-changer, given the high prevalence rate of HIV in South Africa. This product is the most effective HIV prevention measure thus far," said SAHPRA CEO Dr Boitumelo Semete-Makokotlela.
The rapid approval was facilitated through collaboration with the European Medicines for All Procedure (EU-M4all), which enables the EMA to work with participating regulatory authorities to provide scientific opinions on high-priority medicines intended for markets outside the European Union.
Mechanism of Action and Administration
Lenacapavir functions as a capsid inhibitor, targeting the protective shell around the HIV virus's genetic material. By disrupting this shell, the drug prevents HIV from infiltrating and replicating inside CD4 immune cells. Unlike daily antiretroviral pills currently available, lenacapavir requires only two injections every six months, with the medication releasing slowly into the body over this extended period.
SAHPRA specified that the injection "is used to reduce the risk of HIV in adults and adolescents who weigh at least 35 kg, are HIV negative, and are at risk of getting HIV." The regulator emphasized that lenacapavir should always be used in combination with safer sex practices, such as using condoms, to reduce the risk of other sexually transmitted infections.
To ensure immediate protection, patients must also take four 300mg oral tablets—two on the day of the injection and two the following day.
Planned Public Sector Rollout
The Department of Health has indicated plans to launch a limited rollout of lenacapavir at approximately 10% of public sector clinics beginning in April 2026. According to a health department presentation from October, phase one of the rollout will commence in 23 high-incidence districts across six provinces, targeting 360 high-performing public clinics already being prepared for implementation.
Health Minister Dr Aaron Motsaoledi outlined the priority populations for the initial rollout: "In particular, prioritising pregnant and breastfeeding women (PBFW), adolescent girls and young key populations (AGYW), female sex workers (FSW), and men who have sex with men (MSM), would yield the highest impact."
The government plans to provide ongoing support through reminder systems, community follow-ups, and retention programmes to help patients stay on treatment. The programme is expected to expand to more clinics in subsequent years.
Funding and Pricing Strategy
The Global Fund has allocated $29.2 million for the initial rollout, sufficient for approximately 456,000 people over two years. However, studies suggest South Africa will need 1-2 million doses annually to significantly impact the country's HIV epidemic.
A major development in accessibility came with the announcement that from 2027, two generic drug manufacturers from India will offer lenacapavir at $40 per person per year—lower than the current cost of daily prevention pills at approximately $58 per person per year. This pricing is considered affordable and cost-effective for the South African government, as prevention spending can reduce later treatment costs.
Until generic versions become available, South Africa will procure limited amounts from Gilead Sciences, the patent holder, at $60 per person per year. Private donors are covering additional costs, though the full pricing structure has not been disclosed, raising questions from activists about price transparency.
Global Context and Access Concerns
The approval represents significant progress, but access challenges remain. Carlota Baptista, HIV/HCV Access Advocacy Manager at Doctors Without Borders (MSF), noted that while the approval is welcome, "it is a step forward that leaves behind many other countries and people at risk, with no catch-up plan in place."
Within South Africa, the estimated 450,000 people expected to receive lenacapavir in the first year represents more than half of all lenacapavir that will be made available to low- and middle-income countries by global funders initially, yet falls short of the 1-2 million people annually needed to significantly impact the country's epidemic.
Manufacturing and Local Production
Six companies worldwide have licenses to produce generic lenacapavir. Gilead assessed three South African firms—Aspen Pharmacare, Cipla Medpro, and Pharmacare—but none could currently produce the complex active pharmaceutical ingredient required. Discussions continue between Gilead and the South African government about allowing local companies to manufacture lenacapavir using imported API, with support from the Industrial Development Corporation and Technology Innovation Agency.
Competitive Landscape
Lenacapavir has largely overtaken another HIV prevention injection containing cabotegravir, which was registered by SAHPRA in 2022 but has not yet been made available in South Africa's public or private sectors. Long-acting cabotegravir provides two months of protection per shot, compared to lenacapavir's six-month duration.
Research continues on even longer-lasting formulations, with promising early results for a lenacapavir formulation providing a year of protection and new pills offering a month of protection per tablet.
