SAHPRA approves lenacapavir: Transforming HIV prevention in South Africa
The approval of lenacapavir by SAHPRA heralds a new era in HIV prevention in South Africa, offering hope for improved health outcomes.
Quick Answer
The approval of lenacapavir by SAHPRA heralds a new era in HIV prevention in South Africa, offering hope for improved health outcomes.
Key Questions
- What is lenacapavir and how does it prevent HIV?
- Who can receive lenacapavir under SAHPRA's approval?
- How effective was lenacapavir in clinical trials?
- What makes South Africa's approval of lenacapavir significant?
- What are the side effects of lenacapavir?
SAHPRA approved lenacapavir for HIV prevention on October 27, 2025, making South Africa the first African nation to register this twice-yearly injectable PrEP. Clinical trials showed zero HIV infections in cisgender women and 99.9% efficacy overall, offering a breakthrough alternative to daily oral medications for a country with 5.5 million people on antiretroviral therapy.
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Key Takeaways
- Regulatory milestone: SAHPRA registered lenacapavir on October 27, 2025, following Gilead's March 2025 application, using the EU-M4all collaborative review pathway with the European Medicines Agency.
- Clinical efficacy: Phase 3 PURPOSE 1 trial showed zero HIV infections among 2,134 cisgender women and adolescent girls receiving lenacapavir (0 per 100 person-years; 95% CI, 0.00 to 0.19), versus 2.41 per 100 person-years background incidence.
- Dosing innovation: Six-monthly subcutaneous injections following oral initiation on days 1 and 2 eliminate daily adherence requirements compared with daily oral PrEP alternatives.
- Regional impact: South Africa's approval as first African nation positions the country to influence regional access across the MEA region, where the WHO African Region accounts for 50% of global new HIV infections.
What Is Lenacapavir and How Does It Work?
Lenacapavir (brand name Yeztugo) is a first-in-class HIV-1 capsid inhibitor developed by Gilead Sciences. Unlike daily oral pre-exposure prophylaxis (PrEP) options, this long-acting injectable medication targets the HIV capsid protein—a锥形蛋白质 shell that surrounds the viral genetic material.
The capsid inhibitor mechanism works through multiple stages of the viral lifecycle. Lenacapavir blocks viral entry into cells, prevents capsid assembly, and disrupts viral release. This multi-target approach provides potent protection against HIV-1 acquisition with dosing every 26 weeks.
The approved regimen requires an oral initiation phase—two 300mg tablets on day 1 and day 2—followed by subcutaneous injections of 927mg (delivered as two 1.5mL injections) every six months. This schedule maintains therapeutic concentrations that prevent viral establishment.
What Do the Clinical Trial Results Show?
The SAHPRA approval relies on data from two Phase 3 clinical trials: PURPOSE 1 (NCT04994509) and PURPOSE 2 (NCT05502341). Both trials evaluated lenacapavir against background HIV incidence and daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF).
PURPOSE 1 enrolled 5,338 cisgender women and adolescent girls in South Africa and Uganda. Results published in the New England Journal of Medicine showed zero HIV infections among 2,134 participants receiving lenacapavir (0 per 100 person-years; 95% confidence interval [CI], 0.00 to 0.19). By comparison, the background HIV incidence in the screened population was 2.41 per 100 person-years. ClinicalTrials.gov NCT04994509 provides full trial details.
PURPOSE 2 evaluated 3,265 cisgender men, transgender women, transgender men, and gender-nonbinary participants. This trial recorded 2 HIV infections in the lenacapavir group (0.10 per 100 person-years; 95% CI, 0.01 to 0.37) versus 9 infections in the F/TDF group (0.93 per 100 person-years). Background incidence was 2.37 per 100 person-years.
| Trial | Population | Lenacapavir Infections | Incidence Rate | Background Incidence |
|---|---|---|---|---|
| PURPOSE 1 | Cisgender women (SA, Uganda) | 0/2,134 | 0.00 per 100 PY | 2.41 per 100 PY |
| PURPOSE 2 | Men and gender-diverse persons | 2/2,179 | 0.10 per 100 PY | 2.37 per 100 PY |
| Combined | 8,603 total participants | 2/4,313 | 0.05 per 100 PY | — |
The FDA approved lenacapavir for HIV prevention on June 18, 2025, based on these data, with Gilead reporting that over 99.9% of participants remained HIV negative across both trials.
How Did SAHPRA Evaluate Lenacapavir?
Gilead submitted the lenacapavir application to SAHPRA in March 2025. The regulator reviewed the dossier through the EU-M4all (European Medicines for All) procedure—a collaborative pathway enabling EMA and participating regulatory authorities to provide scientific opinions on high-priority medicines intended for markets outside the European Union.
According to SAHPRA's official announcement, Dr. Boitumelo Semete-Makokotlela, SAHPRA CEO, stated: "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."
The approval covers lenacapavir for pre-exposure prophylaxis (PrEP) in combination with safer sex practices. The indication extends to adults and adolescents weighing at least 35 kg who are HIV negative and at risk of HIV-1 infection.
What Safety Data Supports the Approval?
The lenacapavir safety profile comes from 8,603 participants across the PURPOSE 1 and PURPOSE 2 trials. No significant safety concerns emerged during the studies, with patterns consistent across both trials.
Injection-site reactions represented the most common adverse event, occurring in 68.8% of lenacapavir recipients versus 34.9% of placebo injection recipients. These reactions included pain, redness, and swelling at the injection site. Most were mild to moderate in severity.
Discontinuation rates due to injection-site reactions were low: only 4 participants in the lenacapavir group (0.2%) stopped treatment for this reason. The favorable risk-benefit ratio supported regulatory approvals in multiple jurisdictions.
The FDA had previously approved lenacapavir (as Sunlenca) on December 22, 2022, for a different indication—treatment of heavily treatment-experienced adults with multidrug-resistant HIV-1 infection. The FDA approval letter established the treatment-experienced safety profile, while the PURPOSE trials extended understanding to HIV-negative populations.
Why Is This Approval Critical for South Africa?
South Africa carries one of the world's highest HIV burdens. According to WHO data, the country had approximately 5.5 million people receiving antiretroviral therapy in 2021. The WHO African Region accounts for 50% of global new HIV infections, with 26.3 million people living with HIV across the region.
The current standard for HIV prevention—daily oral tenofovir-based PrEP—requires consistent adherence. However, WHO epidemiological data show that adherence challenges limit real-world effectiveness. The twice-yearly lenacapavir schedule removes daily adherence barriers.
South Africa's HIV 95-95-95 cascade data from 2021 show 94% of people living with HIV know their status, 79% of those knowing their status are on treatment, and 91% of those on treatment achieve viral suppression. The gap between diagnosis and treatment initiation represents precisely the population where lenacapavir PrEP could prevent new infections.
What Implementation Challenges Lie Ahead?
Successful lenacapavir rollout requires addressing infrastructure requirements distinct from oral PrEP delivery. The six-monthly injection schedule demands trained healthcare providers capable of subcutaneous administration, cold chain maintenance for the injectable formulation, and patient education about the oral initiation phase.
Access and cost questions remain critical. Injectable cabotegravir—approved by the FDA in 2021 as a two-monthly PrEP option—has seen limited uptake despite excellent efficacy, with some reports suggesting less than 5% of US PrEP prescriptions use the injectable due to clinic resource constraints, insurance coverage, and supply chain complexities.
Pricing and reimbursement mechanisms will determine real-world accessibility in South Africa's dual public-private healthcare system. International funding organizations, including the Global Fund and PEPFAR, may play crucial roles in supporting procurement for at-risk populations.
Regional regulatory harmonization could accelerate adoption across neighboring African nations. The African Medicines Agency establishment aims to streamline such processes, though national implementation varies.
Frequently Asked Questions
What is lenacapavir and how does it prevent HIV?
Lenacapavir is a long-acting injectable HIV-1 capsid inhibitor. It works by blocking the HIV capsid protein, preventing viral entry into cells and viral replication. Administered as subcutaneous injections every six months after an oral initiation phase, lenacapavir provides continuous protection without requiring daily medication adherence.
Who can receive lenacapavir under SAHPRA's approval?
SAHPRA approved lenacapavir for HIV-negative adults and adolescents weighing at least 35 kg who are at risk of HIV-1 infection. The medication must be used in combination with safer sex practices and is indicated for pre-exposure prophylaxis (PrEP) only.
How effective was lenacapavir in clinical trials?
In the Phase 3 PURPOSE 1 trial, zero HIV infections occurred among 2,134 participants receiving lenacapavir (0 per 100 person-years), compared to 2.41 per 100 person-years background incidence. In PURPOSE 2, only 2 infections occurred among 2,179 lenacapavir recipients (0.10 per 100 person-years) versus 9 infections in the daily oral F/TDF group. Overall, more than 99.9% of participants receiving lenacapavir remained HIV negative across both trials.
What makes South Africa's approval of lenacapavir significant?
South Africa became the first African nation to approve lenacapavir for HIV prevention, with SAHPRA's October 27, 2025 registration. This is significant because South Africa has one of the world's highest HIV burdens, with approximately 5.5 million people receiving antiretroviral therapy. The approval positions South Africa as a regional leader in adopting innovative prevention technologies and may accelerate access across the Middle East and Africa region.
What are the side effects of lenacapavir?
The most common side effect of lenacapavir is injection-site reactions, occurring in 68.8% of participants in clinical trials. These reactions were generally mild to moderate. Only 0.2% of participants discontinued the trial due to injection-site reactions. No significant safety concerns were identified in the Phase 3 PURPOSE trials.
Primary Sources
- South African Health Products Regulatory Authority. "SAHPRA Registers Lenacapavir." Published October 27, 2025. https://www.sahpra.org.za/news-and-updates/sahpra-registers-lenacapavir/
- Bekker LG, et al. "Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women." New England Journal of Medicine. 2024;391(13):1179-1191. Published July 24, 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2407001
- Gilead Sciences. "Yeztugo (Lenacapavir) Is Now the First and Only FDA-Approved HIV Prevention Option Offering 6 Months of Protection." Press release. June 18, 2025. https://www.gilead.com/news/news-details/2025/yeztugo-lenacapavir-is-now-the-first-and-only-fda-approved-hiv-prevention-option-offering-6-months-of-protection
- ClinicalTrials.gov. "Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in Adolescent Girls and Young Women." NCT04994509. https://clinicaltrials.gov/study/NCT04994509
- ClinicalTrials.gov. "Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV Infection." NCT05502341. https://clinicaltrials.gov/study/NCT05502341
- U.S. Food and Drug Administration. "Sunlenca (lenacapavir) Approval Package." NDA 215973/215974. Approved December 22, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000Approv.pdf
- World Health Organization. "HIV Data and Statistics." Global Health Observatory. Updated July 2025. https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hiv/strategic-information/hiv-data-and-statistics
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