What are bNAbs, and why do they matter?

Broadly neutralising antibodies (bNAbs) are powerful proteins that the body can use to fight off HIV. Discovered about a decade ago, bNAbs came to light when scientists studied “elite controllers”—the rare individuals, often women, who are able to suppress HIV without medication. These elite controllers produce special antibodies that keep HIV in check naturally. Scientists have since learned how to replicate these antibodies in the lab, creating what could be a revolutionary tool in the fight against HIV.

The RIO study: Pushing the boundaries of HIV control

A key highlight at CROI 2025 was the RIO study from the UK and Europe, which investigated whether bNAbs could control HIV without the need for traditional ART. The study enrolled 68 men who had all been diagnosed within six months of infection and had relatively small HIV reservoirs—meaning the virus had not yet deeply embedded itself in their DNA.

Participants stopped taking ART and instead received two types of long-acting bNAbs. By week 20, 75% of the bNAb-treated group had not experienced viral rebound, compared to just 5% of those on a placebo. Even more striking, 39% remained in viral remission at week 72—nearly a year and a half later.

This suggests bNAbs could offer an alternative to daily ART, with the potential for infusions every six to twelve months. There’s even hope that, over time, a person’s immune system might begin producing its own bNAbs, achieving natural control of the virus—a true “functional cure.” While this remains unproven, ongoing studies, including long-term follow-ups from RIO, aim to find out.

However, bNAbs aren’t a one-size-fits-all solution. Some people may not respond to them due to variations in the virus or the individual’s immune system. Still, for those who do respond, the long-acting nature of bNAbs means fewer treatments and less risk of resistance.

HIV cure research expands: First trial in Africa

In another major first, researchers presented the results of a bNAb cure trial conducted in South Africa—the first of its kind on the African continent. The trial combined bNAbs with Vesatolimod, an immune-boosting cancer drug from Gilead Sciences, and involved 20 women who had been diagnosed early and were on ART for about seven years.

Although HIV rebounded in most participants around 11 weeks after stopping ART—longer than the typical 2–3 weeks—four women remained off treatment with suppressed viral loads for over 18 months. This is a powerful testament to the potential of immune-based strategies, particularly for women, who have long been underrepresented in HIV cure research.

Long-acting ARVs and game-changing prevention tools

For people not suited to bNAb therapy, the future still holds exciting options. Among these is Lenacapavir, Gilead’s long-acting injectable ARV, already available for individuals with multi-drug resistant HIV. Clinical trials are also exploring its use in combination with Islatravir as a weekly oral pill or as part of a six-monthly regimen—offering the potential to dramatically simplify HIV treatment.

Lenacapavir also shows immense promise as pre-exposure prophylaxis (PrEP). Already demonstrating strong results in six-monthly dosing, new data presented at CROI revealed that a single annual injection—at five times the dose—can be just as effective in preventing HIV transmission.

While not yet available as PrEP in high-income countries like Australia, Gilead has licensed generic production for 120 low- and middle-income countries at just $40 USD per year. A once-yearly PrEP option could transform prevention efforts worldwide, particularly for young women in regions hardest hit by HIV.

Stem-like cells and a shrinking reservoir

In a separate study, researchers explored whether it’s possible to shrink the elusive HIV reservoir using genetically modified, HIV-resistant stem-like cells. In a monkey model, scientists infused these CCR5-CD4 Tscm cells—engineered to resist HIV—and observed that they gradually outcompeted the infected cells. The reservoir continued to decline for two years post-treatment, offering hope for long-term control or even eradication of the virus.

HIV, aging, and inflammation

CROI 2025 also tackled issues around aging with HIV—a growing concern as more people live longer with the virus. A Canadian study found that cognitive decline varies widely, but early intervention through exercise and healthy habits may slow the process.

Statins, typically prescribed for high cholesterol, were also found to reduce frailty in older adults with HIV. This supports findings from the REPRIEVE trial (IAS 2023), which showed that statins also reduce inflammation and cardiovascular risk—particularly important given the chronic low-level inflammation caused by the persistent HIV reservoir.

Gut health: A new frontier

The gut, home to much of our immune system, is particularly affected by HIV. New findings revealed that people with HIV often have a “non-secretor” phenotype in the gut—associated with lower levels of fucose, a sugar crucial for intestinal health. This leads to higher inflammation, microbial translocation (bacteria leaking into the bloodstream), and accelerated aging. Improving gut health could be key to managing HIV-related comorbidities in the future.

Women, HIV, and hormone therapy

Finally, an important conversation at CROI centred on menopause and HIV. Women with HIV tend to reach menopause earlier and with more severe symptoms. Hormone replacement therapy (HRT) was highlighted as a promising intervention not only to ease these symptoms but also to reduce inflammation and protect against cardiovascular disease.

The new HOT trial in the U.S. will explore how modern, body-identical HRT can support women living with HIV during menopause and beyond. It also aims to educate healthcare providers on the critical importance of women’s health in HIV care.

The road ahead

CROI 2025 wasn’t just a conference; it was a turning point. The advances shared this year—particularly around bNAbs—have elevated the conversation from what might be possible to what is possible. We’re seeing real, measurable progress in finding a functional cure, enhancing treatment options, and improving the quality of life for people with HIV.

Science is moving fast, and with the IAS HIV Science Conference set to take place in Kigali, Rwanda, this July, the momentum shows no sign of slowing. I’ll be there ‘in-person on an IAS scholarship, to bring you the latest updates—and, hopefully, more good news.

The dream of an HIV cure feels closer than ever.

Links

• Watch CROI 2025 session recordings – public access from 15/4/2025
• Lenacapavir and bNAbs twice-yearly treatment trial
• RIO HIV cure trial
• Melbourne HIV Cure research using a cancer drug – NIVO-LD study
• Read more about the latest HIV cure research in Australia at hivcure.com.au
• If you live in Melbourne and would like to enrol in a clinical trial sign up to the Victorian HIV cure volunteer database