How Does Twice-Yearly HIV Prevention Drug Achieve 99.9% Effectiveness: Game-Changing Results Scientists Didn't Expect

## Lenacapavir achieves **99.9% HIV prevention effectiveness** with twice-yearly injections, requiring only **two shots per year** compared to daily oral medications, based on results from PURPOSE clinical trials involving **over 5,000 participants** across multiple countries. The HIV prevention landscape just experienced its most dramatic shift in decades. **FDA-approved lenacapavir** (marketed as Yeztugo) doesn't just improve on existing treatments—it revolutionizes them with a twice-yearly injection that eliminates the daily pill burden entirely. The clinical trial results read like a medical impossibility. In the **PURPOSE 1 trial**, **zero participants out of 2,134 women** who received lenacapavir acquired HIV. Zero. In the **PURPOSE 2 trial**, only **2 participants out of 2,179** in the lenacapavir group became infected—compared to **9 infections** in the smaller control group taking daily oral medication. This breakthrough represents a paradigm shift in preventive medicine, similar to revolutionary developments like [RNA cancer vaccines](../health/rna-cancer-vaccines-breakthrough-2025) and [precision medicine advances](../health/precision-medicine-revolution-2025) that are transforming healthcare outcomes. > "Seeing these high levels of efficacy — at almost 100% — in an injectable that people only have to take every six months is incredible." > > — **Dr. Colleen Kelley**, Emory University Research Lead The **96% effectiveness rate** in the PURPOSE 2 trial specifically studying men and gender-diverse individuals represents **the highest HIV prevention efficacy ever recorded in clinical trials**. --- ## The Twice-Yearly Revolution Changes Everything Traditional HIV prevention requires daily oral medication—a regimen that creates adherence challenges, stigma concerns, and daily reminders of risk. **Lenacapavir's subcutaneous injection** delivered every six months eliminates these barriers entirely. The dosing schedule involves an initial two-day period with both injection and oral medication, followed by **927 mg subcutaneous injections every six months**. More than **75% of study participants** surveyed preferred the twice-yearly approach, with over half reporting strong preference based on feeling more protected (**69% cited this reason**) and confident about not missing doses (**77% agreement**). > "Long acting antiretrovirals offer new hope for those who are not able to take oral medications." > > — **Dr. Carlos del Rio**, Leading HIV Researcher This addresses a critical gap for populations where daily pill-taking creates social, cultural, or practical barriers to consistent HIV prevention. --- ## Global Impact Potential Exceeds Expectations The clinical trials enrolled participants across **88 sites in 7 countries**: Peru, Brazil, Argentina, Mexico, South Africa, Thailand, and the United States. Importantly, **over 70% of participants were Black or Hispanic individuals**—populations disproportionately affected by HIV globally. **Science journal named lenacapavir its 2024 "Breakthrough of the Year,"** recognizing its potential to fundamentally alter the trajectory of the HIV epidemic. **Daniel O'Day, Gilead's CEO**, described the approval as "a historic day in the decades-long fight against HIV" and "one of the most important scientific breakthroughs of our time." The **World Health Organization welcomed the FDA approval** and announced it will release updated guidelines for injectable lenacapavir at the International AIDS Conference. Early research into **once-yearly formulations** shows promising preliminary results, suggesting even longer-acting options may emerge. --- ## Revolutionary Medical Paradigm Shift Lenacapavir represents more than incremental improvement—it demonstrates how innovative drug delivery can transform disease prevention entirely. The move from daily pills to twice-yearly injections removes adherence barriers that have limited PrEP effectiveness for **nearly two decades**. **Gilead Sciences** has committed to broad access through insurance coverage negotiations, an Advancing Access program for reduced out-of-pocket costs, and medication assistance for uninsured individuals. With **FDA approval secured** and international regulatory submissions underway, **lenacapavir could reach global HIV hotspots by early 2026**. The implications extend beyond HIV prevention alone, establishing a precedent for **long-acting injectable therapies** that could revolutionize treatment of other chronic conditions requiring daily medication adherence. This innovation parallels other medical breakthroughs transforming patient care, from [AI-powered liquid biopsy cancer detection](../health/ai-liquid-biopsy-cancer-detection-breakthrough) to [CRISPR therapeutic advances](../science/crispr-therapeutics-breakthrough-2025) that promise to cure previously untreatable conditions. As we witness these converging medical revolutions, lenacapavir stands as proof that **the future of medicine lies in making powerful treatments as simple and accessible as possible**. ## Sources 1. [Gilead Sciences - Yeztugo FDA Approval](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) - Official FDA approval announcement 2. [Emory University Clinical Trial Results](https://news.emory.edu/stories/2024/11/hs_lenacapavir_trial_27-11-2024/story.html) - PURPOSE 2 trial findings 3. [NPR - HIV Prevention Drug Breakthrough](https://www.npr.org/sections/goats-and-soda/2025/06/18/g-s1-73130/hiv-prevention-drug-lenacapavir-fda-breakthrough) - Expert analysis and context 4. [World Health Organization Statement](https://www.who.int/news/item/19-06-2025-fda-approval-of-injectable-lenacapavir-marks-progress-for-hiv-prevention) - Global health implications 5. [The Lancet - Pharmacokinetics Study]() - Once-yearly formulation research 6. [BioPharma Dive - Clinical Trials Analysis](https://www.biopharmadive.com/news/biotech-pharma-clinical-trials-watch-2025/736120/) - Industry perspective