For oral medications that prevent new HIV infections to be effective, it is crucial for patients to adhere to certain protocols, such as attending regular doctor’s visits every three months and, most importantly, maintaining consistency in their medication regimen. Oral antiretrovirals, specifically pre-exposure prophylaxis (PrEP) drugs like Truvada, have proven to be highly effective at preventing HIV when taken daily, but their effectiveness diminishes significantly if not taken as directed.
PrEP works by maintaining a steady level of HIV medications in the bloodstream, making it much harder for the virus to establish an infection if exposed. However, research has shown that many patients face challenges in consistently taking the medication every day, leading to less effective protection. This inconsistency can be attributed to a variety of factors, including forgetfulness, the burden of daily pill-taking, stigma, and challenges in accessing healthcare. These issues highlight the need for alternative HIV prevention methods that are more convenient and accessible to those at risk.
A groundbreaking study from Emory University and Grady Health System introduces a promising solution in the form of a twice-yearly injection of Lenacapavir. The results, published in the New England Journal of Medicine, show that this injectable form of PrEP significantly reduces the risk of HIV infection, offering a 96% reduction in risk overall. This makes Lenacapavir a much more effective option than the daily oral PrEP, especially for individuals who struggle with adherence.
Colleen Kelley, MD, the lead author of the study and a professor at Emory University School of Medicine, emphasized the potential of this injectable, noting the high efficacy of the treatment despite its infrequent dosing schedule. “Seeing these high levels of efficacy—at almost 100%—in an injectable that people only have to take every six months is incredible,” she said. This convenience could prove transformative for populations at higher risk for HIV who have historically struggled to maintain the daily oral medication regimen.
The study, a randomized, double-blind, Phase III clinical trial, compared the effectiveness of the two HIV prevention strategies. Of the 2,179 participants in the Lenacapavir group, 99% did not contract HIV during the trial period. This was in stark contrast to the 9 new infections that occurred among the 1,086 participants taking Truvada. Furthermore, adherence to the injectable medication was found to be higher than adherence to the oral pill regimen, underlining the potential of long-acting treatments in improving overall outcomes.
Kelley pointed out that while PrEP has long been known for its effectiveness, adherence to daily medication has been a persistent issue. “What we see over time is that about half of people who start taking daily oral PrEP stop within a year due to various factors,” she explained. These factors include difficulties accessing healthcare, financial barriers, social stigma, and the simple inconvenience of daily pill-taking. For individuals facing such challenges, an injectable option like Lenacapavir could be a game changer, as it requires far less frequent dosing.
The clinical trial also stood out for its inclusivity, as it included racially, ethnically, and gender-diverse participants from regions around the world, including Peru, Brazil, Argentina, Mexico, South Africa, Thailand, and the United States. This is significant because it reflects the populations most disproportionately affected by HIV. In particular, cisgender gay men, Black, and Hispanic individuals represent the majority of new HIV diagnoses in the U.S., making these groups particularly important to study when developing new prevention methods. According to the study, more than half of all new HIV infections in the U.S. in 2022 occurred among cisgender gay men, with 70% of those infections affecting Black or Hispanic individuals.
The inclusion of these populations is also crucial in ensuring that new HIV prevention tools, like Lenacapavir, are accessible and effective for the groups that need them most. Dr. Valeria Cantos, the principal investigator at Grady Memorial Hospital’s clinical trial site, noted the importance of ensuring diverse representation in research. “At Grady, our focus is on increased representation of underserved and vulnerable populations,” she said. “Grady is an established, trusted research site because of its commitment to equity.”
In addition to the clinical trial’s diversity, the research team also took steps to ensure the accessibility of information and materials for participants. For example, at the Grady research site, medical materials were available in Spanish, and bilingual staff were recruited to assist Spanish-speaking participants. This attention to detail ensured that the trial was inclusive of individuals who might otherwise face barriers to participating in clinical research due to language or cultural differences.
Kelley also stressed that while the results of this trial are encouraging, they underline a critical gap in current HIV prevention efforts. “We are not reaching everyone we need to reach with our current HIV prevention interventions,” she said. People who are disproportionately impacted by HIV often face significant healthcare disparities, making it difficult for them to consistently access or adhere to daily oral PrEP. In such cases, long-acting injectable medications like Lenacapavir could offer a more feasible alternative, significantly improving HIV prevention for those most at risk.
With the Phase III clinical trial now completed and submitted to the U.S. Food and Drug Administration (FDA) for review, there is hope that Lenacapavir could receive approval for commercial use by 2025. If approved, this injectable medication could provide a vital new option for HIV prevention, especially for people who struggle with the daily pill regimen.
Carlos del Rio, MD, chair of the Department of Medicine at Emory University School of Medicine, highlighted the importance of Lenacapavir in the broader context of HIV prevention. “The results of this study add to the armamentarium of novel tools for HIV prevention,” he said. “Long-acting antiretrovirals offer new hope for those who are not able to take oral medications.” However, del Rio also pointed out the need to ensure equitable access to these new tools. “The challenge is now to roll out and make these tools available and accessible in an equitable way—only then we will see new HIV infections dramatically decreased locally and globally.”
Source: Emory University