With PrEP Effort Lagging, Positive Results for Twice-Yearly Lenacapavir May Give a Lift | AIDS 2024

Because of the lack of the vaccine, preexposure prophylaxis (PrEP) with antiretroviral medication is currently seen by most HIV/AIDS experts as the best way to prevent new infections. But PrEP programs, in the U.S. and internationally, are lagging way behind their goals. The dependence on PrEP and the shortfalls in the current programs made the positive results for lenacapavir reported at the International AIDS Society’s AIDS 2024 this week even more noteworthy.

Lenacapavir is administered as a subcutaneous injection in the abdomen twice year. Currently most PrEP regimens involved taking pills daily. Experts and other are hoping that that a relatively long-acting injectable will be far more acceptable

Results from the PURPOSE 1 trial, which were published simultaneously yesterday in The New England Journal of Medicine, showed that none of the 2,134 cisgender women randomly assigned to lenacapavir PrEP were infected with HIV and that serious side effects were rare, affecting 4% of those in the lenacapavir.

“These data confirm that twice-yearly lenacapavir for HIV prevention is a breakthrough advance with huge public health potential. If approved and delivered – rapidly, affordably, and equitably – to those who need or want it, this long-acting tool could help accelerate global progress in HIV prevention," Sharon Lewin, president of the Internantional AIDS Society, said in a prepared statement.

Gilead, the maker of lenacapavir and sponsor of the trial, said in a news release yesterday announcing the positive results that it expects to see results from PURPOSE 2, a trial of lenacapavir among cisgender men, transgender men, transgender women and gender non-binary individuals, later this year or early in 2025.

The company said in the news release that it plans to include results from both trials its filings for approval from the FDA and drug regulators “to ensure lenacapavir for PrEP can be approved for multiple populations and communities most in need of additional HIV prevention options.” Presuming that lenacapavir is approved, questions about how Gilead will price the preventive product and possible technology transfer to generic companies are looming on the horizon as most of the new 1.3 million HIV infections that occur annually are in low and middle-income countries .

Lenacapavir is approved as a treatment and marketed under the name Sunlenca for that purpose.

Moupali Das, M.D.. M.P.H.

Experts have been urging drug developers to include pregnant women and adolescents in HIV/AIDS trials. Corresponding investigator Moupali Das, M.D., M.P.H., executive director, HIV clinical research, at Gilead and her colleagues reported that there 510 pregnancies among the study participants, including 193 in the lenacapavir group. None of those who were pregnant acquired HIV. The trial included 124 women ages 16or 17.

The PURPOSE 1 results were heralded at the meeting but did not catch anybody off guard. The trial was halted last month and the positive results announced in a Gilead news release on June 20. The IAS presentation and publication in The New England Journal of Medicine (NEJM) filled in details but the outline of the positive results was known.

Das and her co-authors noted the other PrEP options, which include a vaginal ring that delivers dapivirine and Apretude (cabotegravir), which is also injected but on a more frequent every-other-month schedule, as well as the daily pills. “Nevertheless,” they wrote in the discussion section of the NEJM paper, “PrEP use remains suboptimal among women, particularly in populations with disproportionate HIV incidence, including young women, women in Africa, women of color in the United States, and migrant women in multiple countries. Twi-yearly lenacapavir offers a highly effective and discreet choice to potentially improve PrEP use among women.”

The Purpose 1 trial enrolled cisgender women at 25 sites in South African and three in Uganda. They were randomly assigned to lenacapavir, once-daily Descovy (200 milligrams [mg] of emtricitabine and 25 mg of tenofovir alafenamide), or once-daily Truvada (200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate). The trial did not include a placebo group because an untreated group was deemed unethical. Instead, the main comparison was the background incidence of those screened for the trial, which was calculated at 2.41 infections per 100 person-years.

With no cases, the incidence of infections in the lenacapavir group was 0 per 100 person-years. There 39 infections among the 2,136 randomly assigned to Descovy, which worked out to 2.02 infections per 100 person-year and 16 among the 1,068 assigned to Truvada, which worked out to 1.69 infections per 100 person-years. In the Descovy and Truvada groups, most of those who became infected with HIV had levels of antiretroviral medicine in their blood that suggested that they were not taking the pill on a daily basis.

The results reported in NEJM didn’t have set off any strong signals about lenacapavier as PrEP. The most common side effect were injection-site reactions; 69% (1,470 of 2,138) had those. But all but four were categorized as mild (grade 1 or 2). Aside from injection-site reactions, the most common side effect in the lenacapavir group was urinary tract infection (14.4%), headache (13.3%) and genitourinary chlamydia infection (14%). Those proportions were similar to those seen among the participants who were assigned to the Descovy and Truvada arms of the trial.