Over the last 45 years, HIV infection has affected more than 91 million people. Nevertheless, complete clearance of the disease (remission) remains an extremely rare event and is typically associated with the radical procedure of stem cell transplantation.
Recent clinical trials demonstrate that a limited group of patients achieved a “functional cure.” This means their immune system was able to effectively establish viral control without daily antiretroviral (ARV) medication, a control that lasts for months or even years. This achievement is a fundamental breakthrough because continuous, lifelong ARV therapy, along with the potential risk of side effects, represents a massive daily burden for patients.
The results of two independent studies align: a special population of immune cells, precursors of stem-cell-like memory killer T cells ( memory T cells), was found to be a critical factor in long-term viral control after the cessation of antiretroviral therapy. Detailed deciphering of the functional mechanisms of these cells is the key to creating new therapeutic strategies.
Although antiretroviral drugs have saved millions of lives by controlling HIV, the virus remains hidden in the body’s “reservoirs.” Therefore, upon stopping the therapy, the virus usually reactivates rapidly (actively replicates) within a few weeks. Functional cure, however, prevents this reactivation through immune control, significantly improving patients’ quality of life and reducing chronic inflammatory processes associated with ARV drugs, which increase the risk of heart and other organ diseases.
Research Details:
Two separate clinical studies on functional cure show impressive results:
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Ragon Institute Study: Led by David Collins, the Ragon Institute team analyzed data from four trials where the cessation of ARV therapy was preceded by the administration of long-acting, broadly neutralizing antibodies (bNAb). According to the study, 14% to 22% of patients successfully maintained viral control for at least two months, even after the effectiveness of the bNAb waned. Notably, one patient maintained viral control without treatment for over 7 years.
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UCSF Clinical Trial: The second research trial conducted by the University of California San Francisco (UCSF) team focused on a complex treatment strategy. This strategy included a combination of three components: bNAb, an experimental vaccine, and a drug aimed at reducing viral reservoirs. Seven out of ten participants managed to maintain effective HIV control for months without any additional therapy. This result represents the longest continuous control period recorded to date in similar clinical trials, indicating the great potential of the combined approach.
Immunological Basis of Viral Control
Both research groups agree that stem-cell-like memory T cells are tightly correlated with maintaining long-term viral control.
These “stem-like” T cells are characterized by their ability to self-renew and undergo rapid proliferation (expansion) as soon as HIV reactivation begins. They function as an early warning system, and their ability for rapid expansion is critically important for effectively suppressing viral reactivation. “We just haven’t seen that with interventions previously,” noted Rachel Rutishauser, co-leader of the UCSF study. Thus, stimulating these stem-cell-like cells could be the basis for new therapies.
At this stage, it is not precisely determined why the concentration of stem-cell-like cells is higher in some patients. However, David Collins hypothesizes that upon stopping ARV therapy, the long-acting bNAb antibodies remaining in the body delay the onset of viral reactivation. This temporary delay allows the T cells to begin proliferation and fully prepare for the fight against the virus. If antibodies do not slow down viral activation, T cells might react too late, and immune control over the virus might not be achieved.
It must be noted that these T cells are only one component of the complex puzzle of the immune system. The UCSF study also highlights the effect of the vaccine: antibodies bound to viral particles cause intense stimulation of other immune reactions, which significantly contributes to maintaining ultimate control.
Michel Nussenzweig, one of the study authors, emphasizes that for long-term HIV control, “Every little bit is going to count.” Against the background of additional clinical trials and research, the vision of freeing millions of people from the routine burden of daily medication may soon become a reality, radically transforming the future of HIV medicine.
წყარო: Science
