Ask AI
Back Back
Highlighting HIV Prevention
Highlighting HIV Prevention: Pivotal Studies Presented EACS and ID Week 2025

Released: November 21, 2025

Kenneth Ngure
Kenneth Ngure, MPH, MSc, PhD
Activity Information

Activity

Progress
1
Course Completed
Continue
Key Takeaways
  • There were no clinically significant drug–drug interactions between lenacapavir and hormonal contraceptives in PURPOSE 1, with higher persistence to twice-yearly lenacapavir vs daily oral FTC/TDF for PrEP demonstrated in PURPOSE 2.

New Findings From LEN Studies
As with other recent HIV conferences, updates on the efficacy and safety of twice-yearly lenacapavir (LEN) for HIV pre-exposure prophylaxis (PrEP) in 2 phase III randomized trials featured prominently at IDWeek and European AIDS Clinical Society (EACS) 2025.

One abstract assessed drug–drug interactions between LEN and commonly used progestin-type long-acting (LA) hormonal contraceptives in PURPOSE 1 participants. Investigators hypothesized that since LEN is a CYP3A inhibitor, coadministration with LA contraceptives has the potential to increase concentrations of hormonal contraceptives metabolized by the CY3PA pathway.

Specifically, this study evaluated etonogestrel (ENG), medroxyprogesterone acetate (DMPA), and norethindrone enanthate (NET-EN) concentrations in a subset of participants who received LEN and were taking these contraceptives at baseline through 26 weeks of follow-up.

Among the participants on uninterrupted LA hormonal contraceptives through Week 26, plasma concentrations of DMPA and NET-EN were comparable with baseline levels, irrespective of dose, frequency, or dosing changes across visits. An upward trend was observed with ENG, but did not reach statistical significance. Therefore, investigators concluded that LEN coadministration resulted in no clinically significant changes in the pharmacokinetics of ENG, DMPA, or NET-EN LA hormonal contraceptives. Overall, these findings indicate that LEN can be used with standard LA or oral hormonal contraceptives without requiring dose modifications.

To me these data are particularly important for sub-Saharan Africa, where women at the highest risk of HIV are also the women at high risk of unwanted pregnancies. Effective LA methods of preventing HIV that can be used concurrently with LA methods to prevent unwanted pregnancies are urgently needed.

Facilitating PrEP Access
Persistence to PrEP is essential for achieving optimal protection. The PURPOSE 2 study evaluated persistence on twice-yearly subcutaneous (SC) LEN for PrEP vs with daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). Among the participants in the preselected 10% of the study population that was assessed for persistence, significantly more participants persisted with SC LEN vs FTC/TDF, whereas persistence with SC LEN was similar to persistence with placebo injections in the FTC/TDF group. These findings provide additional supportive data for the rollout of LEN for PrEP among cisgender men and gender-diverse people.

Cost will also be a key determinant of whether LEN is widely adopted, especially in low- and middle-income countries in sub-Saharan Africa. A previous study estimated that generic LEN could be produced for $41 per person, per year.

Following recent licensing and manufacturing advances, an updated analysis was urgently warranted. A new estimate, presented at IDWeek, reported that generic LEN is now projected to cost as little as $25 per person, per year, for 5 million people, accounting for modest manufacturing improvements expected to occur in the near future. The authors noted that this translated to generic LEN costing less than oral alternatives, and priced 1000 times lower than the launch price of approximately $28,000. These data are very reassuring in light of recent HIV funding cuts.

Transitioning From HIV PEP to Oral PrEP
The last study I want to highlight was conducted at IRCCS San Raffaele Scientific Institute, Milan and  underscores the need for continued efforts to offer multiple methods of HIV prevention that suit different lifestyles. A study assessing linkage to HIV PrEP in a real-world setting measured whether participants who started a 28-day course of postexposure prophylaxis (PEP) initiated either daily or on-demand PrEP once PEP was completed. PrEP counselling was offered at each scheduled follow-up visit.

Overall, 80.9% of participants completed PEP follow-up through Day 28, 19.1% were lost to follow-up, and fewer than half of individuals who used PEP eventually transitioned to PrEP. These results emphasize the importance of tailored HIV prevention counseling that includes PrEP and PEP for individuals at continued risk of HIV. As PEP and PREP programs in sub-Saharan Africa continue to scale up, lessons learned from other regions of the world may offer valuable insights into improving PEP and PREP uptake.

Your Thoughts
How do you think tolerability and number of injections per year will affect uptake of each PrEP modality? Leave a comment to join the discussion!

Continue