The Promise of Immunotherapy to Cure HIV
A groundbreaking study at the amfAR Institute for HIV Cure Research leads to potential breakthroughs in controlling the virus long-term
By Andrea Gramatica, PhD
December 19, 2025
 Drs. Rachel Rutishauser and Steven Deeks, University of California, San Francisco
For nearly three decades, antiretroviral therapy (ART) has turned HIV from a fatal infection into a manageable chronic condition, where the virus is not eliminated but kept fully in check or, in clinical terms, “suppressed.” However, if ART is interrupted the virus quickly comes back. For that reason, a major goal of cure research is sustained post-treatment control: maintaining low or undetectable viral levels without ongoing ART.
An amfAR-funded clinical study offers a genuine step in that direction.
Published in Nature, this clinical study recently reported long-term HIV control in a subset of participants who had been given a combination immunotherapy and whose antiretroviral therapy (ART) had been subsequently stopped under closely monitored medical supervision.
Led by Drs. Rachel Rutishauser and Steven Deeks, this HIV cure study was designed to test whether pairing immune-based interventions could delay or prevent viral rebound after stopping ART, and to identify immune factors associated with what scientists call “post-treatment control,” a phenomenon occasionally seen in certain individuals who, after receiving certain types of cure-based therapies, can suppress the virus without completely eliminating it.
The intervention was structured as a combination regimen delivered while participants were on ART, followed by dosing with a combination of two broadly neutralizing antibodies (bNAbs) and an immune-stimulating agent (a TLR9 agonist). Participants then received further bNAb infusions as they discontinued ART under close clinical monitoring. The rationale was to limit viral rebound early and, at the same time, support immune responses that could contribute to longer-term control of the virus.
In the trial, time to viral rebound was delayed relative to what is typically observed in treatment interruption studies, resulting in several participants demonstrating post-treatment control. One participant, in particular, remained aviremic (no virus could be detected in their blood) for more than 18 months after stopping ART. Others maintained low viral “set points” for months. As expected in a study of this type, outcomes were heterogeneous across individuals, underscoring that post-treatment control remains difficult to achieve consistently.
So, what happened in these study participants after administration of the bNAbs + TLR9 agonist? A central contribution of the study were the mechanistic insights into what distinguished participants who controlled the virus (i.e., the “controllers”) from those who didn’t (i.e., “non-controllers”). The analyses didn’t show that control was explained by “more antibody in the blood,” or by simple measures of reservoir size, or by pre-interruption immune readouts; rather, they revealed that controllers had an expansion and activation of a particular subset of their immune cells called CD8+ T cells, which are typically responsible for the elimination of cancerous or infected cells. Control of the virus tracked with an early expansion of activated CD8+ T cells suggests that the immune system can regenerate effective virus-fighting cells over time.
HIV cure research has many candidate interventions, but fewer measurable immune signatures that can be used to guide selection, dosing, timing, and participant stratification in future trials. By linking post-treatment control to a defined pattern of CD8+ T-cell dynamics during the interruption period, the study provides concrete endpoints that can be tested and refined.
These approaches are still experimental and not ready for clinical use outside trials. The next steps will require larger studies, comparison groups, and continued work to simplify regimens while improving consistency and durability of control.
amfAR supports this kind of research because progress toward sustained ART-free control will likely come from iterative clinical testing paired with detailed immunologic and virologic measurements. This study adds both: evidence that combination immunotherapy can be associated with delayed rebound and post-treatment control in some individuals, and a clearer view of the immune features that may help explain why.
Dr. Gramatica is amfAR’s vice president and director of research.
Contact:
Robert Kessler (he/him)
Program Communications Manager
amfAR, The Foundation for AIDS Research
robert.kessler@amfar.org
Source: amfAR, The Foundation for AIDS Research
https://www.amfar.org/news/the-promise-of-immunotherapy-to-cure-hiv/
"Reproduced with permission - amfAR, The Foundation for AIDS Research"
amfAR, The Foundation for AIDS Research
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