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Long acting HIV PrEP Africa
Long-Acting HIV PrEP in Sub-Saharan Africa: Strategies for Successful Implementation

Released: January 13, 2026

Flavia Matovu Kiweewa
Flavia Matovu Kiweewa, MBChB, MSc., PhD
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Key Takeaways
  • Adherence to daily oral PrEP continues to be a challenge in Africa, especially among young women.
  • Long-acting PrEP offers a new strategy for addressing adherence and persistence barriers.
  • Effective implementation of long-acting PrEP will require healthcare professionals and institutions alike to bridge key gaps in care.

Pre-exposure prophylaxis (PrEP) works, but only if people can stick with it. I’d like to share with you the story of one person’s journey, which shows how a person’s relationship with PrEP can change over time.

In the vibrant town of Entebbe, where the breeze from Lake Victoria carries the scent of rain and earth lives Peter (not real names), a 36-year-old man who has sex with men. Peter currently works as a peer educator at the Most-At-Risk-Populations Clinic in Mulago. After attending a health workshop in late 2017, he suddenly felt a wave of anxiety. He realized that his lifestyle required protection against HIV. He began taking the daily pill, but it wasn't out of empowerment; it was out of a deep, cold fear.

Peter held the small bottle in his hand, the plastic cool against his palm. Inside were 30 blue pills, a monthly promise of protection called PrEP. He knew this daily ritual was a smart choice for his health, but as he placed the bottle in his medicine cabinet, he felt a flicker of unease. He was worried about what friends might think if they saw it, or the labels people might place on him. To Peter, the bottle felt louder than it looked.

The daily pill became a heavy shadow. Every morning, the rattle of the bottle felt like a chain. It was a constant reminder of risk and a burden he had to carry. Peter felt trapped by the schedule, his mind always tethered to the medicine cabinet.

As weeks turned into months, the initial weight of the routine began to lift, but so did Peter’s focus. On nights when he stayed out late or weekends spent relaxing, the pill stayed in the cabinet. "I’m not seeing anyone right now," he would tell himself, "my risk is basically zero." The daily habit started to crumble as he convinced himself that protection was only necessary when he felt "at risk," rather than as a steady shield.

That relaxed feeling often vanished following some nights of uncertainty. Suddenly, the "low risk" he had leaned on felt like a fragile glass floor. Fear replaced his indifference. Peter would reach out to his healthcare provider for post-exposure prophylaxis (PEP). He later began setting 3 different alarms on his phone, rushing home if he forgot his PrEP dose. The struggle to keep up with daily pill taking wasn’t it out of self-care anymore; he was doing it out of a heavy, constant anxiety about contracting HIV that hummed in the back of his mind.

Feeling exhausted by the mental tug-of-war, Peter decided to visit the clinic. He met with Dr Aris, a kind physician who listened without judgment. "The daily pill is a great tool, Peter," Dr Aris said gently, "but if it’s causing you this much stress, we have other ways to keep you safe. Healthcare should fit your life, not the other way around."

Dr Aris suggested "on-demand" PrEP, often called the 2-1-1 method. It meant Peter would only take the pills around the times he knew he would need protection; 2 before, 1 after, and 1 more the next day. Peter liked the idea of not having a daily reminder. For a while, this felt like the perfect compromise, giving him back his sense of control without the daily burden of the bottle.

Although the on-demand method works for some, Peter found the timing difficult to manage and never fully trusted that this method was enough to keep him safe. He wanted something even simpler, something that didn't require him to do math or keep track of tablets.

One afternoon, at his routine PrEP refill visit, Dr Aris told Peter about a new option: an injectable form of PrEP called cabotegravir. "It is 1 shot every 2 months," he explained gently. "No daily pills, no counting hours. Just long-lasting protection."

Peter decided to make the switch. In the quiet exam room, Dr Aris prepared the injection. It was a quick, sharp pinch in his muscle, over in just a few seconds. "That’s it," Dr Aris said, discarding the needle. "You're protected for the next 2 months." Peter felt a strange sense of relief. For the first time in a year, he didn't have to worry about a pill bottle or a timer.

The next morning, Peter felt a bit of a sting. His muscle was sore, making him limp slightly when he walked to the kitchen. Later that afternoon, a dull headache settled behind his eyes. He sat on his bed, feeling a bit discouraged, and wondering if the new path was turning out to be just as difficult as the previous. "Is this better than the pills?" he pondered, pressing a cool cloth to his forehead. He reached out to the clinic, and Dr Aris reassured him that these side effects were common and usually temporary.

True to the doctor's word, the discomfort faded within a few days, and for the first time in years, the burden of pill taking was gone, replaced by a quiet confidence that moved with him as we went about his routine errands. By the time Peter’s second appointment arrived 2 months later, the injection site didn't hurt nearly as much, and the headaches never returned. Peter realized he hadn't thought about HIV or pill schedules in weeks. The routine of the "shot" became a simple, bi-monthly errand, no more complicated than getting a haircut or visiting the dentist.

Now, Peter walks along the shore of Lake Victoria with a lightness he hadn't felt since he first held that blue pill bottle. His protection is invisible, tucked away in his body rather than sitting on a shelf. He realized that the journey to health isn't always a straight line, but by speaking up and exploring his options, he found the rhythm that worked for him. He was no longer defined by a pill; he was just Peter, living his life to the fullest. He looks forward to a newer long-acting injectable option that only requires him to visit the clinic twice instead of 6 times per year. This will be the ultimate freedom, no daily bottles, no mental gymnastics of the 2-1-1 on-demand method, and significantly fewer trips to the clinic! A protected life that will allow him to love, to live, and breathe the Entebbe air with a heart at rest.

Peter’s journey underscores a central truth in HIV prevention: effectiveness on paper doesn’t automatically translate to effectiveness in practice. Daily oral PrEP has transformed HIV prevention globally. However, its success hinges on consistent adherence—a challenge that persists across many African settings, especially among young women.

Many people have reported daily pill taking as burdensome and stigmatizing, considering the same therapies that are used for HIV treatment are also used for prevention. “How will I convince my neighbor, who is HIV positive, that I am HIV negative when we are taking the same medications and picking them up at the same health facility?” asked a young woman, who had to discontinue her daily oral PrEP due to a lack of privacy.

Mild adverse events, coupled with lifestyle factors like high mobility, further complicate PrEP adherence. These barriers contribute to high discontinuation rates that are often driven by perceived low risk, structural challenges (eg, long distances to access health facilities), and psychosocial factors, such as fear of disclosure or partner opposition. This can lead to high drop-out rates and wasted program resources.

In Africa, both uptake of and persistence with daily oral PrEP have been unacceptably low. According to data from the Uganda Ministry of Health, for every 10 individuals who initiate PrEP for HIV, only 2 persist with treatment at 1 year.

Enter Long-Acting PrEP
The long-acting HIV PrEP options—injectable cabotegravir with a maintenance dose that is administered every 2 months, and lenacapavir with a maintenance dose that is administered every 6 months—offer durable protection. These are not just effective therapies, they are potentially life-changing tools for empowerment. These innovations in HIV PrEP, plus others in the pipeline (eg, MK-8527, a monthly pill), address what I see as the core limitations of daily oral PrEP. They will help eliminate the daily pill burden, reduce the need for taking visible medication at home—and, thus, the stigma associated with it—and should improve persistence rates.

For healthcare professionals (HCPs), long-acting PrEP introduces new clinical considerations. HIV-negative status must be confirmed before each injection to minimize drug resistance. Staff training on injection technique and site management is essential, as is strict adherence to follow-up schedules. Although injection-site reactions are generally mild to moderate in severity, counselling patients remains important. Cost and supply chain logistics, including cold-chain requirements, may pose significant challenges for some injectables. And, finally, retention is critical since patients must return every 2 or 6 months to receive maintenance treatment with cabotegravir or lenacapavir, respectively.

Future of Long-Acting PrEP in Africa
Despite these hurdles, the potential impact in Africa is profound. Over the next 5 years, long-acting PrEP could be a game-changer for young women and other key populations who are disproportionately affected by HIV. Integration into existing general health services will likely complement, not replace, daily oral PrEP. With more options available, patients are now better positioned to find a method that works best for them. If affordability, supply, and access improve, these therapies will significantly reduce HIV incidence.

However, success depends on addressing gaps in implementation. Cost-effectiveness analyses are needed to guide scale-up strategies. Real-world implementation of science research will ensure PrEP interventions align with patient preferences. Health systems must prepare through robust workforce training, supply chain strengthening, and framework monitoring. Finally, long-term safety data across diverse populations, in addition to data from open-label extension phase studies from pivotal trials, will be critical.

HCPs play a vital role in supporting informed decision-making. Shared decision-making tools, culturally sensitive education, and individualized risk assessments can empower patients to choose the option that best fits their needs and lifestyles. By dispelling myths and emphasizing benefits, HCPs can ensure that long-acting PrEP fulfills its promise.

Although long-acting PrEP represents a major advance in the HIV prevention landscape, it also signals a future where HIV prevention is simpler, more practical, and profoundly empowering. With strategic implementation and patient-centered care, long-acting PrEP can overcome adherence challenges and accelerate progress toward ending the HIV epidemic in Africa.

Your Thoughts
How often are you prescribing long-acting options to your patients as their preferred PrEP? You can get involved in the conversation by posting a comment below.

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