The twice-yearly injection could transform HIV prevention efforts

The twice-yearly injection could transform HIV prevention efforts

Preventative therapies for human immunodeficiency virus type 1 (HIV-1) have skyrocketed over the past decade. A once-daily pill called PREP, or pre-exposure prophylaxis, has been a powerful tool for HIV prevention—only if people take it consistently and can access a pharmacy routinely.

In 2022, Gilead Sciences, Inc. received US Food and Drug Administration (FDA) approval for lenacapavir, a twice-yearly injectable drug for adults with multidrug-resistant HIV. A number of clinical studies have shown that this medication could also serve as a preventive medication, specifically helping to encourage them to make an effort to fill their prescriptions or stick to a daily pill regimen.

Now the well-tolerated drugs have been approved by the FDA as new preventative medications forall adultsand adolescents weighing at least 35 kg who are at risk of acquiring HIV. Joe Eron, MD, the Herman and Louise Smith Distinguished Professor of Medicine and director of the clinical core at the UNC Center for AIDS Research, played a hand in the clinical trials that led to the drugs' FDA approval.

This is a game-changing development in our area. I honestly think that if public health and medical institutions can deploy it into rural populations, these drugs could help end the HIV epidemic not only in North Carolina, but in the United States as a whole. “

Joe Eron, MD, clinical trial site director, UNC School of Medicine

The injection, which has a six-month period of effective protection, will help mitigate access gaps and prevent further infections caused by low medication adherence.

The HIV epidemic in North Carolina

Here in North Carolina, the HIV epidemic still lingers. Approximately 38,634 people are living with HIV in the “Tar Heel State,” placing NC in the “top ten” for statewide HIV rates.

The bloodborne infection can be transmitted through anal or vaginal sex or the needles or syringes with an HIV-positive partner. Certain groups of people are more likely to acquire HIV than others, depending on their behaviors and geographic locations.

Infectious disease researchers and doctors like Eron have found that HIV disproportionately affects those living in rural, underserved areas in the South, particularly young men who have sex with other men.

This is because many rural areas of the South are considered healthcare deserts – or areas where people cannot easily travel to pharmacies, primary care providers, hospitals and low-cost health centers. These can pose a major challenge for people who need to take their prescriptions - and do so discreetly.

“North Carolina is no exception,” Eron said. "We see that young men of color who have sex with other men are unfamiliar with the preparation due to stigma and lack of access to healthcare. This long-lasting injection is critical because it can only be given twice a year in a private, medical setting."

Zero infections and 100% efficacy in a phase 3 clinical trial

In summer 2021, investigators initiated two different Phase 3, multicenter trials to evaluate the safety and efficacy of lenacapavir in high-dose populations: Purpose 1 and Purpose 2.

Purpose 1 included 5,000 sexually active women across Uganda and South Africa to determine how lenacapavir versus Gilead Sciences, Inc. once-daily Truvada (emtricitabine/tenofovir disoproxil fumarate) and once-daily oral Descovy (emtricitabine/tenofovir alafenamide) compares.

Researchers published their results in theNew England Journal of MedicineIn July 2024. Lenacapavir became 100% effective, with no infections in 2,138 participants. The injectable drug also demonstrated superior prevention of HIV infections compared to those who received once-daily Truvada.

The Purpose 2 clinical trial was designed to test the efficacy and safety of lenacapavir for priming in cisgender men and gender diverse individuals (i.e., transgender women, transgender men, and gender non-binary) who have sex with men. The trial had a broader international scope compared to Purpose 1 and took place in 92 locations in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States.

Once again, lenacapavir showed high effectiveness in participants. The results, published in theNew England Journal of MedicineIn November 2024, it found that approximately 99.9% of participants in the lenacapavir group were protected against HIV infection. There were only two cases of HIV among 2,179 participants. Compared to a daily dose of Truvada, lenacapavir was 89% more effective at reducing HIV infections.

“Through the purpose trials, we found that lenacapavir can effectively prevent HIV infection in the body,” said Eron. "But it is also safe. The studies showed no toxicity in the liver, kidney or other parts of the body."

The results of the last two experiments were so impressive thatScienceLenacapavir called2024 breakthrough of the year.

High adherence to lenacapavir and injections

Medical compliance is crucial. To prevent breakthrough infections, it is incredibly important for patients to take their medications as prescribed and continue taking them throughout the entire regimen. The oral preparation takes approximately 7-22 days of consistent daily use to achieve full effectiveness.

In Study 1, the results were consistent with other reports from people taking priming medications. At the one-year mark, researchers found that 84.1% of participants who received Descovy did not adhere to their medication schedule. In the Truvada group, approximately 93.0% of participants had low medication adherence.

Eron and colleagues are now trying to get the drug to people who are at highest risk of HIV infection - such as those just leaving prison, receiving treatment for intravenous drug abuse, or people without transportation. The drug's long protective properties are crucial as people adjust to their new lives and may not be able to accommodate frequent follow-up visits.

“When people at risk leave prison or received opioid therapy, they are at highest risk [of getting infection] in the next three to four months,” Eron explained. A single shot could actually be the protection they need to keep themselves and their partners healthy. “

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