Preventative therapies for HIV-1 (Human Immunodeficiency Virus type 1) have made leaps and bounds over the past decade. A once-daily pill named PrEP, or pre-exposure prophylaxis, has been a stalwart for HIV prevention-but only if people take it consistently and can routinely access a pharmacy.
In 2022, Gilead Sciences, Inc., received U.S. Food and Drug Administration (FDA) approval for lenacapavir, a twice-yearly injectable medication for adults with multidrug-resistant HIV. A number of clinical trials have shown that this medication could also serve as a preventative medication-one that can specifically help those struggling to pick up their prescriptions or stick to a daily pill regimen.
Now, the well-tolerated medication has by the FDA as a new preventative medication for all adults, as well as adolescents weighing at least 35kg, 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 clinicals trials leading up to FDA approval of the medication.
Joe Eron, MD
"This is game changing development in our field," said Eron, who was principal investigator of the clinical trial site at the UNC School of Medicine. "I honestly think if public health and medical institutions can deploy it to rural populations, this medication could help end the HIV epidemic, not only in North Carolina, but in the United States overall."
The injection, which boasts a six-month-long period of effective protection, will help mitigate healthcare access gaps and prevent further infections brought on by low medication adherence.
The HIV Epidemic in North Carolina
Here in North Carolina, the HIV epidemic still lingers. About 38,634 people are living with HIV in the "Tar Heel State", placing NC in the "Top Ten" in terms of nationwide HIV rates.
The blood borne infection can be transmitted through anal or vaginal sex, or the sharing needles or syringes with an HIV-positive partner. Certain groups of people are more likely to get HIV than others, depending on their behaviors and geographic locations.
A map depicting newly diagnosed HIV rates in North Carolina in 2023. Credit: NC DHHS 2023 HIV Surveillance Annual Report Summary
Infectious disease researchers and physicians, like Eron, have seen that HIV disproportionately affects those living in rural, underserved areas in the South, especially young men of color who have sex with other men.
This is because many rural areas of the South are considered to be healthcare deserts-or areas where people cannot easily travel to pharmacies, primary care providers, hospitals, and low-cost health centers. These can pose a huge challenge for people who need to grab their prescriptions-and to do so discreetly.
"North Carolina is no exception to that," said Eron. "We see that young men of color who have sex with other men are not comfortable with taking PrEP, due to stigma and lack of healthcare access. This long-lasting injection is critical because it can be given in a private, medical setting just twice a year."
Zero Infections and 100% Efficacy in One Phase 3 Clinical Trial
In the summer of 2021, researchers initiated two different phase 3, multicenter trials to study lenacapavir's safety and effectiveness for PrEP in highly vulnerable populations: PURPOSE 1 and PURPOSE 2.
PURPOSE 1 enrolled 5,000 sexually-active women throughout Uganda and South Africa to determine how lenacapavir fares against Gilead Sciences, Inc.'s once-daily Truvada (emtricitabine/tenofovir disoproxil fumarate) and once-daily oral Descovy (emtricitabine/tenofovir alafenamide).
Science's 2024 Breakthrough of the Year was lenacapavir. Credit: Sara Gironi Carnevale
Researchers published their results in the New England Journal of Medicine in July 2024. Lenacapavir was shown to be 100% effective, with zero infections across 2,138 participants. The injectable medication 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 PrEP in cisgender men and gender-diverse individuals (i.e. transgender women, transgender men, and gender non-binary individuals) who have sex with men. The trial had a wider international scope compared to PURPOSE 1 and took place across 92 sites in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States.
Yet again, lenacapavir demonstrated high efficacy in participants. The results, published in the New England Journal of Medicine in November 2024, 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 once-daily Truvada, lenacapavir was 89% more effective at reducing HIV infections.
"Through the PURPOSE trials, we found that lenacapavir is effective at preventing HIV infection from taking hold in the body," said Eron. "But it is safe, too. The studies did not demonstrate toxicity in liver, kidney, or other parts of the body."
Results from the past two trials were so impressive that Science named lenacapavir its 2024 Breakthrough of the Year.
High Adherence to Lenacapavir and Injections
Medical adherence is crucial. In order to prevent breakthrough infections, it is incredibly important for patients to take their medications as prescribed and to continue taking them for the entire regimen. Oral PrEP takes about 7-22 days of consistent daily use to reach full effectiveness.
In the PURPOSE 1 trial, results were consistent with other reports in people taking PrEP medications. At the one-year mark, researchers found that 84.1% of participants receiving Descovy were not adhering to their medication schedule. In the Truvada group, approximately 93.0% of participants had low medication adherence.
Eron and colleagues are now looking to get the drug to people who are at highest risk of HIV infection-such as those who are just leaving prison, receiving treatment for intravenous substance abuse, or those living without transportation. The long protective properties of the drug are key, as people are adjusting to their new lives and may not be able to come in for frequent follow-up visits.
"When people at risk leave prison or received opioid therapy, they're at highest risk [of getting infection] over the next three to four months," explained Eron. "A single shot could actually be the protection they need to keep themselves and their partners healthy."
