Lenacapavir vs Cabotegravir: South Africa’s HIV Prevention Jab Shift

South Africa is poised to roll out a recent twice-yearly HIV prevention injection, lenacapavir (LEN), at 360 government clinics. This arrival, however, comes as another preventative measure, long-acting cabotegravir (CAB-LA), quietly exits the field. The story of CAB-LA offers valuable lessons about the complex interplay of cost, politics, and logistical groundwork in public health initiatives, and how those lessons are now informing the implementation of LEN.

A Costly Barrier to Prevention

Both lenacapavir and CAB-LA are antiretroviral medications designed for pre-exposure prophylaxis, or PrEP – preventing HIV-negative individuals from contracting the virus through sexual contact. While both are administered via injection, CAB-LA requires injections every two months, while LEN is given twice a year. The key difference, and ultimately the downfall of CAB-LA in South Africa, was price. At approximately $180 (R2,900) per person annually, CAB-LA was roughly four times more expensive than generic lenacapavir. This cost proved prohibitive for widespread public health implementation.

The potential for PEPFAR – the U.S. President’s Emergency Plan for AIDS Relief – funding to bridge this cost gap existed, but was thwarted by aid stop-work orders issued by the Trump administration in 2025. As reported by the U.S. Department of State, these orders effectively froze the donation before a single dose of CAB-LA could be administered through the program.

Building a Foundation for LEN

Despite its stalled rollout, the work invested in CAB-LA wasn’t entirely lost. Advocates emphasize that the training programs, logistical systems, and real-world data collection efforts established to support CAB-LA are now providing a crucial foundation for the successful implementation of lenacapavir. This groundwork will streamline the process of introducing LEN into the existing healthcare infrastructure.

The arrival of LEN is being supported by a significant partnership between Gilead Sciences, and PEPFAR. Gilead announced in September 2025 that it would provide lenacapavir at no profit, aiming to reach up to two million people in low- and lower-middle-income countries over three years. Gilead is also actively working with PEPFAR and the Global Fund to assess product demand and secure manufacturing capacity.

Understanding PrEP and the Role of Injectables

PrEP, or pre-exposure prophylaxis, involves taking medication to prevent HIV infection in individuals who are at risk. Traditionally, PrEP has been administered as a daily oral pill. However, injectable options like CAB-LA and LEN offer a potentially more convenient and discreet alternative, which could improve adherence and ultimately reduce transmission rates. The convenience of less frequent dosing is a significant advantage, particularly for individuals who may struggle with daily medication adherence.

The Cost Comparison: LEN vs. CAB-LA

The significant cost difference between lenacapavir and CAB-LA highlights a critical challenge in global health: ensuring access to innovative medications in resource-limited settings. While CAB-LA demonstrated promising efficacy, its high price tag rendered it unsustainable for widespread use in South Africa, despite the potential for PEPFAR support. LEN, being more affordable, presents a more viable option for achieving broad population-level impact.

It’s important to note that the cost of medications can vary depending on factors such as generic availability, manufacturing processes, and negotiated pricing agreements. The commitment from Gilead to provide LEN at no profit is a crucial step in making this preventative measure accessible to those who require it most.

Lessons Learned from CAB-LA’s Experience

The story of CAB-LA serves as a cautionary tale about the importance of considering not only the scientific efficacy of a medical intervention but also its economic feasibility and the political landscape surrounding its implementation. The frozen PEPFAR donation underscores how external factors can derail even the most promising public health initiatives.

However, the experience also demonstrates the value of investing in infrastructure and capacity building, even when a particular intervention faces obstacles. The groundwork laid for CAB-LA has paved the way for a smoother rollout of LEN, maximizing the impact of available resources. As Bhekisisa reports, the systems and data collected during the CAB-LA preparation phase are now being leveraged to ensure LEN’s successful integration into the South African healthcare system.

What to Expect with the LEN Rollout

The rollout of lenacapavir at 360 government clinics in South Africa represents a significant step forward in HIV prevention efforts. The twice-yearly injection offers a convenient and effective alternative to daily oral PrEP, potentially increasing adherence and reducing new infections. The partnership between Gilead and PEPFAR, coupled with the lessons learned from the CAB-LA experience, positions LEN for a more successful implementation.

Ongoing monitoring and evaluation will be crucial to assess the impact of LEN on HIV incidence rates and to identify any challenges that may arise during the rollout. Continued investment in training healthcare workers, strengthening supply chains, and addressing potential barriers to access will be essential to maximize the benefits of this innovative preventative measure.