CROI 2026: Persistence and expansion of the HIV reservoir on long-term ART

14 April 2026. Related: Conference reports, Cure-related research, Basic science and immunology, CROI 33 (Retrovirus) 2026.

Simon Collins, HIV i-Base

A fascinating and compelling review of the current understanding of the HIV viral reservoir and a brief history of the key research was given in a plenary talk by John Mellors from the University of Pittsburgh.

This covered establishing the size of the reservoir (likely 10 x 10(11) cells with replicant-competent HIV in 1 million to 100 million), when and how these cells integrate and hide, with differences between men and women, and strategies to overcome the reservoir.

Recent studies have reported notable responses using monoclonal and autologous antibodies in order to delay or sustain HIV viral rebound off-ART, including in the RIO study. Predictors of responses include activation-induced CD8 markers with ELISpot immune parkers in the absence of circulating virus. Updated results from RIO were also presented at CROI this year. [2]

Next steps include more complicated multi-immune interventions and intensive dosing time schedules for example in ACTG 5374 and the UK AbVax studies that are both still enroling. [3, 4, 5, 6]

References

1. Mellors JW. HIV Reservoir: Persistence and Expansion Under Long-Term ART. Plenary lecture, CROI 2026, Denver.
   https://www.croiwebcasts.org/console/player/55147
2. Edgar J et al. Altered Viral Kinetics at ATI After Dual LS-bNAbs Plus ART: A Preliminary Analysis of RIO Arm B. CROI 2026, Oral abstract 134.
   https://www.croiconference.org/abstract/1206-2026/ (abstract)
   https://www.croiwebcasts.org/console/player/55099 (webcast)
3. clinicalTrials.gov. Evaluation of Safety Immunogenicity and Efficacy of a Triple Immune Regimen in Adults Initiated on ART During Acute HIV-1.
   https://clinicaltrials.gov/study/NCT06071767
4. ACTG website press release.
   https://actgnetwork.org/article/actg-announces-launch-of-clinical-trial-evaluating-combination-of-three-novel-immune-based-therapies-for-hiv-cure/
5. clinicalTrials.gov. Combination Vaccination and Broadly Neutralising Antibody Therapy in HIV (AbVax).
   https://clinicaltrials.gov/study/NCT07054931
6. Abvax website.
   https://www.abvaxstudy.org/