CROI 2026 Celebrated Progress, Looked Toward the Future of HIV

The Conference on Retroviruses and Opportunistic Infections (CROI) 2026, which took place in Denver, Colorado, from February 22 to 25, featured 3 full days after the opening session that were full of educational sessions, breaking research, and talks on moving forward in HIV amid the present obstacles in research and funding. With so much to take in across the conference, all attendees were able to leave feeling like they had learned even more about infectious diseases than they ever had before.

Educational Sessions Focused on Cure, Prevention

Every morning at CROI started with a detailed discussion on an important topic in infectious diseases, including how to meet the moment, the current state of sexually transmitted infections, and how glucagon-like peptide-1 receptor agonists could play a role in HIV care. This was most evident in the Wednesday morning session, featuring Kevin O. Saunders, PhD, from the Duke Human Vaccine Institute, where the concept of an HIV vaccine was discussed in front of the eager audience.

During his lecture, Saunders emphasized that a vaccine was paramount to preventing new infections of HIV. Even though there have been promising breakthroughs in long-acting pre-exposure prophylaxis (PrEP), the limited access to PrEP around the world makes a vaccine all the more necessary. Therapeutic and preventive vaccines are the 2 main types of vaccines that are being looked into presently, focused on curing the disease and preventing the disease, respectively.

Although there have been some challenges, preclinical trials have shown some success, including those aimed at engaging rare B cells and guiding them toward neutralizing antibodies. Neutralization signatures, structural signatures, and genetic signatures are all used to measure the clinical success of these vaccines. Machine learning and artificial intelligence may be used in the future to accelerate the development of the vaccines, including the use of generative models to identify the optimal envelope sequences for neutralizing antibodies.

“Successful, sequential vaccines need to have the fewest components possible and require the fewest immunizations possible,” concluded Saunders. “mRNA vaccines may need to substitute for protein-based immunogens in some cases to reduce the cost and hasten the production of multicomponent vaccines.”

Breaking Research Highlighted Promising Strides in Prevention

Among the many breaking research sessions was a session aptly titled “From Breakthroughs to Backbones: The Evolving Landscape of HIV PrEP,” which featured several oral presentations of abstracts that highlighted results of breaking new research. This included updated results of the PURPOSE 1 (NCT04994509) and PURPOSE 2 (NCT04925752) trials, where lenacapavir is continuing to be looked at for both safety and efficacy in sexual minorities.

In the first abstract, presented by Nkosiphile Ndlovu, MBChB, from the University of Witwatersrand in Johannesburg, South Africa, updated safety and efficacy data were presented from the phase 3 PURPOSE 1 trial from the end of the randomized blinded phase.¹ PURPOSE 1 has focused primarily on cisgender adolescents and young women aged 16 to 25 years living in South Africa and Uganda.

Through the end of the randomized blinded phase, there were 2 incident HIV infections in the 2134 participants who had been in the subcutaneous lenacapavir group who received the dose every 26 weeks. This was compared with 77 incident HIV infections in the remaining 3204 participants using an oral daily pill.

“For [lenacapavir], this corresponds with an updated HIV incidence of 0.07 per 100 person-years, consistent with high efficacy and a very low number of infections,” said Ndlovu.

One of the participants who contracted HIV had been receiving their doses on time and had been diagnosed with chlamydia at week 52 before their HIV diagnosis at week 65. The other participant had been diagnosed with HIV after discontinuing lenacapavir and transitioning to open-label tenofovir disoproxil fumarate/emtricitabine (F/TDF). The diagnosis of HIV came 16 months after their last injection.

“This finding still positions twice-yearly subcutaneous lenacapavir as a powerful, durable, low-burden HIV prevention option for one of the populations most urgently needing innovation,” Ndlovu concluded.

Updated results from the PURPOSE 2 trial,² with data from the end of the randomized blinded phase, were also presented during the session by Valeria D. Cantos, MD, an associate professor in the Department of Medicine at Emory University. The PURPOSE 2 trial primarily enrolled cisgender men and gender-diverse individuals who have sex with men.

A total of 2179 participants received lenacapavir every 26 weeks and 1086 received F/TDF daily. The updated results showed that 3 participants in the lenacapavir arm contracted HIV through the end of the randomized blinded phase compared with 12 in the F/TDF arm. This amounted to an incidence of 0.11 per 100 person-years for those on twice-yearly lenacapavir. The new HIV infection in the lenacapavir arm was identified at week 52 after the patient received all injections on time. The patient had a history of rectal chlamydia at screening and week 26 and rectal gonorrhea at week 26.

“In this extended analysis, twice-yearly subcutaneous lenacapavir for PrEP remained highly efficacious and well-tolerated among cisgender men and gender-diverse people who have sex with men through the end of the randomized blinded phase of the PURPOSE 2 study,” Cantos concluded.

Moving Forward in the HIV Space

Among sessions held at CROI, “Sleepless in Denver: Impact of Funding Changes on HIV Care” focused on how the funding cuts to the President’s Emergency Plan for AIDS Relief (PEPFAR) were affecting the treatment of HIV abroad and at home, including 47% of respondents to a survey of clinics around the world citing that the PEPFAR cuts caused some disruption to HIV-related care.³

The Monday plenary session featured a lecture from Ilesh Jani, PhD, from the Mozambique National Institute of Health in Maputo, Mozambique.⁴ The session focused on how researchers can meet the moment in the HIV space through the 4 I’s, focusing on integration, inclusion, innovation, and impact. This includes coming up with new means of service delivery of medication, investing in community-based care, and integrating HIV care as part of primary health care.

Overall, there was something for everyone at CROI 2026. As HIV and the HIV space continue to evolve, the gathering of experts is more important than ever to celebrate the progress that has been made and set a plan for the future of addressing the epidemic.

References

1. Ndlovu N, Malahleha M, Singh Y, et al. Twice-yearly subcutaneous lenacapavir for PrEP: updated HIV-1 incidence and safety data in PURPOSE 1 at the end of the randomized blinded phase. Presented at: Conference on Retroviruses and Opportunistic Infections 2026; February 22-25, 2026; Denver, CO. Abstract 128.
2. Cantos VD, Mngadi K, Supparatpinyo K, et al. Lenacapavir for PrEP: HIV-1 incidence and safety from PURPOSE 2 at the end of randomized blinded phase. Presented at: Conference on Retroviruses and Opportunistic Infections 2026; February 22-25, 2026; Denver, CO. Abstract 129.
3. Bonavitacola J. Budget cuts have wide-ranging impact on PrEP adherence at home and abroad. AJMC. February 24, 2026. Accessed March 2, 2026. https://www.ajmc.com/view/budget-cuts-have-wide-ranging-impact-on-prep-adherence-at-home-and-abroad
4. Bonavitacola J. The 4 I’s: how HIV prevention, treatment can move forward in challenging times. AJMC. February 23, 2026. Accessed March 2, 2026. https://www.ajmc.com/view/the-4-i-s-how-hiv-prevention-treatment-can-move-forward-in-challenging-times