Objective 1: Lenacapavir results “highly anticipated”

The HIV community will soon be seeing twice-yearly data from the PURPOSE 1 clinical trial. Rena Capa Building Preliminary results have shown it to be 100% effective in preventing infection, so it is now being used for pre-exposure prophylaxis.

Linda Gayle Becker, PhD, MBChB, director of the Desmond Tutu HIV Centre at the University of Cape Town in South Africa, will present the results on 24 July at the International AIDS Conference in Munich, Germany.

of Objective 1 Test The results are “very promising,” said Monica Gandhi, MD, director of the UCSF Bay Area AIDS Research Center in San Francisco. Medscape Medical NewsTrial sponsor Gilead Sciences announcement In June, the company announced it was stopping the blinded phase of the trial and moving to open-label dosing of lenacapavir for all HIV community-infected participants. Carelesssaid Gandhi.

Objective 1 is to evaluate pre-exposure prophylaxis with the HIV-1 capsid inhibitor lenacapavir administered subcutaneously twice a year and Descovy administered orally once daily (Emtricitabine The study included 5,338 girls and women aged 16-25 years at risk of HIV infection in South Africa and Uganda. The control group received Truvada (emtricitabine 200 mg and tenofovir alafenamide 25 mg) once daily. Tenofovir disoproxil fumarate 300mg).

Promising early results

The intermediate results are HIV infection HIV infections were reported among 2,134 women receiving lenacapavir. Among 1,068 women receiving Truvada, 16 HIV infections were reported, for an incidence rate of 1.69 per 100 person-years. Among 2,136 women receiving Descovy, 39 HIV infections were reported, for an incidence rate of 2.02 per 100 person-years.

These interim results have infectious disease experts eagerly awaiting more details.

“Long-acting PrEP has the potential to be a breakthrough in ending HIV infection,” says Jenelle Stewart, DO, MPH, an infectious disease specialist at Hennepin Healthcare in Minneapolis. “While taking a medication every day works for some, for others it is impractical or undesirable. No one method works for everyone, and having the freedom to choose and modify a PrEP method to fit your life is central to its impact at the individual and community levels.”

Dr. Paul Sachs, chief of infectious diseases at Brigham and Women's Hospital in Boston, said twice-yearly dosing of lenacapavir is attractive because other long-acting injectable PrEP treatments still require dosing every two months. “One of the challenges with currently available injectable PrEP is that patients need to come into the clinic every two months — six times a year instead of twice a year,” Dr. Sachs said.

The capsid inhibitor lenacapavir is a new class of drug for HIV that could help fight resistance, said Matthew Spinelli, M.D., PrEP medical lead at the University of California, San Francisco. “The really exciting aspect is that this is a different class than the main treatment classes we have today,” he said.

Cabotegravir Spinelli said the drug, another long-acting injectable PrEP option, has had problems with resistance, which has compromised the primary treatment strategy. “So the fact that this prevention option is not in the integrase strand transfer inhibitor class and that we didn't see resistance is also a really exciting and unprecedented aspect of this study,” he said.

Remaining questions

But the community still has plenty of questions that clinicians are hoping to find answers to at the conference. Of particular interest is how well participants adhered to their medication regimens. “How many people stay on treatment in this study? That might be a good indicator of feasibility,” Spinelli says. “It's not real-world data, but how engaged people are in this study and how well it stays is another indicator of how well it's accepted and feasible.”

Side effects will also be closely scrutinized. One reported side effect is nodules at and around the injection site. “Lenacapavir is viscous, and when injected subcutaneously, it can cause nodules that can remain for weeks, sometimes months,” Sacks said. “We need to know if anyone has discontinued treatment because of the nodules. How bothersome were they? How disturbing were they, physically or psychologically?”

Access to appropriate treatment at an affordable cost is a long-term consideration.Rilpivirine The combination, approved by the U.S. Food and Drug Administration in 2021, is being rolled out in a limited capacity, Stewart and Spinelli said.

“Access and scale-up efforts are needed,” Stewart said. “Cabotegravir has had very limited deployment, and its real-world impact has fallen short of its potential value due to lack of access, affordability and clinical infrastructure.”

Spinelli also worries about whether the drug will be available to those who need it most. “Will this be another groundbreaking option that's inaccessible due to issues with logistics, patents, costs, generic production and lack of political will?” he asked. “Will we see the same thing repeated with lenacapavir?”

Becker's first step at AIDS 2024 will be to present the trial's final results in a presentation. “I look forward to hearing more from the PURPOSE 1 trial team about participants' experiences with the injection, details of breakthrough cases, and suggestions for next steps,” Stewart said.