Daniel Kiesa

The conversation around HIV prevention has reached a moment of real momentum. New long-acting options like cabotegravir (CAB-LA) and lenacapavir (LEN) offer something many people have long asked for: protection that doesn’t require a daily pill. The excitement is warranted. But much of the current focus remains front-loaded on awareness, launch, and initiation. What risks being overlooked is what happens next.

Starting PrEP is an event. Staying on PrEP is a system.

As HIV prevention moves toward bi-monthly and bi-annual injections, success will depend less on how many people start and more on how well programs support continuation. Long-acting PrEP is fundamentally different from daily oral PrEP, and patterns of uptake and persistence are unlikely to mirror those seen with oral PrEP. These products require their own evidence base grounded in real-world use across different communities, settings, and life circumstances.

Challenges with adherence and persistence for daily oral PrEP among high-risk populations in sub-Saharan Africa are well documented, underscoring the need for longer-acting PrEP options. Expanding PrEP choice has helped improve coverage, and early evidence suggests that longer-acting options may support better continuation. LEN holds particular promise. Its six-month dosing interval could further reduce barriers by minimizing clinic visits and daily burden.

At the same time, the long interval between injections introduces new questions. No PrEP product to date has required such a long gap between doses. Programs will need to understand what kinds of reminders, touchpoints, or integrated services help people return on time.

This matters not only for individual protection, but also health system efficiency. Initiating someone on injectable PrEP is more resource-intensive than maintaining them. The first visit typically requires longer counseling, more screening, and additional commodities compared to a continuation visit. For LEN, this difference is also visible at the commodity level:

*agreements indicate a $17 ceiling price for the required tablets

When someone drops off after a single dose, the system absorbs the highest costs without realizing the full prevention opportunity. This is not an argument against innovation or choice, far from it. It’s a reminder that designing for continuation is as important as designing for uptake.

It’s also important to recognize that PrEP use is not always linear. Many people use HIV prevention during periods of higher risk and pause when circumstances change. Some products may be better suited to on-again, off-again use than others. Understanding how different populations move in and out of prevention, and how long-acting products fit into those patterns, will be critical.

Ultimately, the next phase of HIV prevention depends on better evidence. Programs need real-world data on continuation and re-engagement, disaggregated by age, gender, geography, and service delivery context. Just as importantly, that evidence must be shared widely, so lessons learned in one setting can inform smarter approaches elsewhere.

If long-acting PrEP is going to move from promising launch to lasting impact, retention can’t be an afterthought. It has to be built into how we plan, measure, and learn because prevention only works if it continues.