The search for a way to control HIV without antiretroviral therapy (ART) continued to generate both promising signals and sobering setbacks at the recent Conference on Retroviruses and Opportunistic Infections (CROI 2026) in Denver. Here are five highlights.
In the second phase of the RIO cure trial, participants who had originally received a placebo were given two broadly neutralising antibodies (bnAbs). More than half maintained low or undetectable viral loads for over 20 weeks after stopping ART, and two remain off treatment after more than a year. In this phase of the trial, the bnAbs were given six months before the treatment interruption – ensuring that any direct antiviral effect of the antibodies had waned – making the delayed rebound a stronger signal of lasting immunological change.
African research teams presented two studies with children with HIV exploring the prospects for remission – long-term viral control without ART. A South African study showed that a subset of children given ART very early after birth were able to maintain viral suppression after stopping treatment. Researchers in Botswana gave a similar group of children three bnAbs before stopping antiretrovirals. All ten children assessed maintained undetectable viral loads on the antibodies alone, and the next phase of the research will see what happens when they stop the antibodies too.
The immune-modulating drug N-803 (Anktiva), given with or without bnAbs, did not produce meaningful delays in viral rebound after stopping ART – results that conflict with early findings presented last year. Some favourable changes in immune markers and the viral reservoir were observed, but the overall picture points to the need for combination approaches rather than any single agent.
A combination of two immune-modulating drugs, budigalimab and trosunilimab, also fell short. The pairing slowed viral rebound after stopping ART in around a quarter of participants, but the effect was not durable, with viral loads eventually rising in those who had initially responded. The researchers concluded that the level of control achieved did not justify further development of this combination.
Research on CD8 cells – immune cells that kill virus-infected cells – offered a new perspective on why some people on long-term ART may be better placed to control HIV than previously thought. Despite decades of treated infection, some long-term ART recipients retain a small population of HIV-sensitised CD8 cells that have the characteristics of newly generated, stem-like cells – capable of rapid proliferation and potent killing activity when re-exposed to HIV. The findings suggest these cells could potentially be harnessed through therapeutic vaccines or immune-boosting agents as part of future cure strategies.
