A PIONEERING proof-of-concept clinical trial has reported the first signs that carefully combined therapeutic strategies may promote post-treatment HIV control, sparking new momentum in the long-standing search for a functional cure.
Curative approaches for HIV have historically failed, aside from rare stem cell transplantation cases, leaving antiretroviral therapy as the mainstay of lifelong management. To challenge this, researchers designed a two-step randomised trial to evaluate whether novel single and combinatorial interventions could alter viral reservoirs and immune dynamics in people with chronic HIV infection and strong baseline immune status.
Thirty participants were equally assigned to one of six arms: standard antiretroviral therapy alone, or therapy combined with one or more investigational strategies. These included antiretroviral intensification, the apoptotic-inducing drug auranofin, vitamin B3 (nicotinamide), and personalised dendritic cell immunotherapy.
After completing the interventions, participants underwent structured treatment interruption. Almost all experienced viral rebound within 14 weeks, yet three individuals stood out: one maintained suppression until Week 84, while two others (both treated with the full combinatorial regimen) sustained viral loads below 1000 copies/mL through the study period. All three post-treatment controllers received nicotinamide-containing regimens and displayed reversal of immune cell epigenetic ageing.
These findings suggest that combining multiple anti-reservoir approaches is safe and, critically, may help a small subset of patients exert immune control without continuous therapy. Though early, the data reignite hope that multi-pronged regimens could one day shift HIV management from lifelong suppression to functional remission.
Reference
Ndhlovu LC et al; SPARC Working Group. Virological and immunological outcomes of combined therapeutic interventions and dendritic cell therapy in people living with HIV. J Infect Dis. 2025; DOI:10.1093/infdis/jiaf430.
