In a packed auditorium at the International AIDS Conference in mid-2024, researchers announced a breakthrough that left many in awe. For the first time ever, a large-scale HIV prevention trial had achieved zero new infections among those receiving the intervention
The intervention was not a vaccine or a daily pill, but a simple injection given just twice a year. This long-acting shot, containing a novel drug called lenacapavir, offered 100% protection in the trial’s participants – a result so dramatic that the study was halted early to make the injection available to all participants
The news sent ripples of hope through the scientific community and beyond, heralding what could be a game-changing new chapter in the fight against HIV.
More than four decades since the first AIDS cases, the world still faces a relentless HIV epidemic. There is no cure and no vaccine yet, despite years of research. As of the end of 2023, roughly 39.9 million people were living with HIV globally and about 1.3 million people are newly infected each year.
For decades, HIV prevention has depended on daily antiretroviral pills. These medications, such as Truvada (TDF/FTC) or Descovy (TAF/FTC), help reduce the risk of infection. Yet, missing even a few daily doses can weaken protection and leave individuals vulnerable. Life’s demands—from privacy concerns to basic forgetfulness—too often stand in the way of consistent pill-taking.
Despite these challenges, millions of people worldwide continue to rely on daily HIV prevention pills. That’s why, when scientists revealed a new option requiring just two injections per year, it sparked a wave of excitement and hope. Early findings suggest this long-acting regimen can be at least 90% more effective than daily pills, primarily because there’s no daily routine to break.
Zero New HIV Infections
In a large-scale study involving over 5,300 participants, those who received lenacapavir injections saw zero new HIV infections during the trial period, compared to those on daily pills who experienced multiple infections. These results, gathered from 25 sites in South Africa and 3 sites in Uganda, surpassed researchers’ initial expectations.
When you see or hear about an injection—maybe during a doctor’s visit or in a conversation about new vaccines—you can now recall lenacapavir. Twice a year, you get a simple subcutaneous shot that maintains a steady level of HIV-preventing medication in your bloodstream. No daily alarm reminders. No anxiety over packing pills when you travel.
This repeated event (two clinic visits per year) acts as a built-in reminder: prevention doesn’t have to be complicated.
Twice-Yearly vs. Daily: Why Lenacapavir Outperforms the Pill
For many, the daily stress of taking HIV prevention pills can be overwhelming—forgetting a dose, facing stigma at the pharmacy, or merely feeling burned out by constant reminders of one’s HIV risk. With lenacapavir, the burden lightens.
In the trial, as in real life, many participants struggled to maintain that habit. Blood tests showed that adherence to the daily regimens dropped off steeply over time, especially among the young women in the study.
By 6 months into the trial, nearly 70% of those in the Descovy pill group had suboptimal drug levels (indicating missed doses), and almost 90% of those in the Truvada group had low adherence.
These lapses explain why dozens of women contracted HIV despite being given potent daily medication. By contrast, over 90% of the women assigned to lenacapavir returned for their second and third injection on schedule.
The vast majority stayed fully protected. A long-acting shot essentially sidesteps the human factor of forgetting pills. Once the injection is administered, the drug slowly releases in the body over months, keeping protection steady without the user needing to remember anything day-to-day.
This is crucial because experts note that when taken consistently, oral PrEP is highly effective; the problem is that consistency is hard to achieve in the real world
Lenacapavir’s format – two doses a year – elegantly solves that problem for many people who struggle with a daily regimen.
Another key advantage of the biannual shot is that it can alleviate stigma and privacy concerns. Daily PrEP pill-taking can inadvertently “out” someone’s HIV prevention efforts, which might invite uncomfortable questions or judgment from others.
“Twice-yearly lenacapavir for PrEP could help address the stigma and discrimination some people may face when taking or storing oral PrEP pills,” explains Dr. Linda-Gail Bekker of the Desmond Tutu HIV Center in Cape Town.
Stories from volunteers in the study reveal relief, excitement, and even renewed optimism. One participant described how her injection “gave me back my evenings.” She no longer worried about taking pills in front of others or slipping up on her schedule.
“This Is Completely in Their Hands”
Consider the experience of a 19-year-old woman in South Africa who knows she’s at risk for HIV. Perhaps she has limited control over condom use with partners, or she finds it hard to stick with a daily pill amidst school, work, or family responsibilities. For her, the option of a discreet injection twice a year could be life-changing.
She can visit a clinic semi-annually, receive her shot, and walk away with six months of protection. There’s no daily reminder of her risk, no pill burden, and nothing her partner or family needs to know. In her words, it might feel like finally having control over her own health.
This scenario is exactly why advocates are celebrating lenacapavir’s success. It empowers individuals – especially young women – to protect themselves. “This is a product that is completely in their hands,” said Winnie Byanyima, the Executive Director of UNAIDS, speaking about the promise of long-acting PrEP for women. “They don’t have to negotiate safe sex with a man… anymore”
In many cultures, women bear the brunt of HIV infection rates but have less power in sexual relationships to insist on condoms or even to suggest HIV prevention, due to social and gender dynamics. A biannual shot that a woman can take independently, without her partner’s involvement, is revolutionary.
Byanyima even hailed lenacapavir as “a feminist product. For girls in Africa, this is magical,” calling it a “miracle tool” for HIV prevention
The lenacapavir injection is also being tested among other populations at risk – and showing equally stellar results. A parallel trial called PURPOSE 2 studied the injection in cisgender men, transgender women and men, and nonbinary people who have sex with male partners (across the Americas, Africa, and Asia). Interim data released in late 2024 revealed that lenacapavir was ~96% effective in preventing HIV in these groups.
In the lenacapavir arm of that study, only 2 infections occurred among over 2,100 participants, versus 9 infections in the daily Truvada pill arm.
Once again, the injectable vastly outperformed the pill (making it ~89% more effective by relative comparison)
“Lenacapavir represents a novel, highly effective tool for prevention and is not dependent upon daily oral adherence.”
said Dr. Colleen Kelley, a principal investigator in the PURPOSE 2 study
Practical Value: How AI Makes a Difference
One of the underappreciated heroes behind these breakthroughs is artificial intelligence. Today’s AI models can sort through massive datasets faster than ever. For the lenacapavir study:
- Monitoring Safety: AI helped researchers track side effects and identify patterns. By analyzing real-time data, scientists could quickly spot any concerning trends.
- Predicting Outcomes: Machine learning tools estimated how different groups—like young women in rural areas or men in urban centers—might respond to this long-acting treatment. This means clinicians could soon tailor prevention plans for each community.
- Optimizing Supply Chains: Even distribution challenges—like storing vials or scheduling injection visits—are simpler to address when AI forecasts demand across various regions.
A New Tool to End an Epidemic?
With such remarkable trial results, lenacapavir injections are being hailed as a potential turning point in the battle against HIV. The prestigious journal Science named long-acting lenacapavir one of the “Breakthrough of the Year” achievements in 2024, describing it as “a pivotal step toward diminishing HIV/AIDS as a global health crisis.”
This optimism is grounded in data. But important questions remain: How quickly can this breakthrough be translated into policy and practice? And will the people who need it most be able to get it?
The path from clinical trial to public health impact can be tricky. As of early 2025, lenacapavir for PrEP is still investigational – it will need regulatory approval before it’s widely available. Gilead Sciences has indicated it will submit the injection for approval, using data from both PURPOSE 1 and PURPOSE 2, to ensure the product can be approved for all key populations (men, women, and others) at once
Regulatory filings and reviews are expected to move swiftly given the compelling efficacy and the unmet need. If approved, health agencies and providers will face the challenge of implementation: delivering a twice-yearly injection in diverse healthcare settings. On one hand, the low frequency of dosing is an advantage (fewer clinic visits than a monthly pill pickup, for example).
On the other, ensuring that people come back every six months for a new shot will require creative strategies – reminders, community engagement, perhaps bundling the injection with other routine health services.
“We’ve never had a 6-month [PrEP] product. I don’t think we have any idea how that will be implemented over the long term in our clinical spaces.”
admitted Dr. Colleen Kelley, reflecting on the need to keep people engaged in care even when they only need to visit twice a year
It’s a good problem to have, and one that healthcare systems can solve with planning and support.
Another crucial consideration is access and equity. Game-changing or not, a preventive drug can only help end an epidemic if it reaches the populations most at risk. HIV has often disproportionately affected low-income countries and marginalized communities. The remarkable results of lenacapavir’s trials will mean little if the actual product is too expensive or scarce for those communities.
Activists and global health organizations are already pushing to ensure lenacapavir doesn’t become available only to wealthy countries or elites. Gilead has announced steps to promote access – including royalty-free licensing agreements to allow generic manufacturers in India, Africa, and other regions to produce affordable lenacapavir for 120 low- and middle-income countries.
This move was applauded as a positive start, potentially shortening the time it takes for developing countries to get a cheaper generic supply. However, some advocates note that even with these licenses, several countries with high HIV burdens are not covered by the current agreements
Continued international pressure will likely be needed to expand access so that no region is left behind. The practical value of a twice-yearly HIV shot is maximized when it’s deployed at scale – reaching people in cities and villages alike, through public clinics, community programs, and outreach to those who might not otherwise seek care.
Looking ahead, experts are cautiously optimistic. We now have powerful tools in our HIV prevention toolkit: highly effective daily pills, an every-two-month injection (cabotegravir), and on the horizon, an every-six-month injection (lenacapavir). The vision of ending the AIDS epidemic no longer seems like a far-fetched dream. If we can combine these biomedical tools with robust public health strategies – education, regular HIV testing, treatment for those living with HIV (to keep the virus suppressed and untransmittable), and perhaps one day a vaccine – the end of HIV transmission could truly be within reach.
“Comprehensive strategies including public health education, behavioral interventions, PrEP and PEP, preventive vaccines, and curative research must be continually developed and optimized for HIV prevention and control.”
a group of virologists wrote in late 2024, noting that only then can we realistically “envision a world without AIDS”
The Road Ahead
It’s vital to remember that no single intervention can end HIV. Public health campaigns, frequent testing, vaccines under development, and even daily pills all work in tandem to keep communities safe. Lenacapavir simply adds a powerful new option to the prevention toolkit. Before it can be rolled out widely, governments must approve it, clinics must be trained to administer it, and insurers need to cover it at accessible rates.
Yet even with these hurdles, the story so far is incredible. The promise of twice-yearly injections that outshine daily pills by a wide margin in effectiveness could redefine HIV prevention. Thanks to advanced AI models, we’re better equipped to ensure that no one gets left behind—whether they live in a city center or a remote region.
Final Thoughts
There’s something remarkably hopeful about seeing the world rally behind new preventive methods. From behavioral strategies to daily pills and now to lenacapavir injections twice a year, HIV prevention has come a long way. We can’t predict the future with certainty, but it’s clear that continued research—powered by AI analysis—and broad public engagement will keep pushing us closer to a world where HIV infections are rare.
Lenacapavir isn’t just a medication. It’s a story of bold innovation, community empowerment, and hope. By understanding how it works and why it matters, you become part of that story—and you can help make sure the momentum toward ending HIV continues to grow.
