Post by Ole Schmeltz Søgaard

Most people living with HIV experience rapid viral rebound when antiretroviral therapy (ART) is stopped. But what enables rare individuals to maintain long-term control without treatment? In a new paper published today in Nature Immunology, we describe three exceptional post-intervention controllers who maintained ART-free viral control for more than 2.5 to over 7.5 years after receiving broadly neutralizing antibodies. Despite having measurable, genetically intact viral reservoirs, viral replication was suppressed by immune pressure. These individuals exhibited strong autologous neutralizing antibodies and highly functional HIV-specific CD4⁺ and CD8⁺ T-cell responses that were already primed before treatment interruption and persisted during ART-free follow-up. In one case, later viral rebound was linked to accumulated viral escape mutations — underscoring the central role of adaptive immunity in maintaining control. Together, these findings support cure strategies that aim not only to target the viral reservoir but also to strengthen and harness durable pre-existing immune responses to achieve sustained HIV remission. This work was led by first author Katie Fisher, a highly talented postdoc in the Søgaard Lab, and would not have been possible without the contributions of our outstanding collaborators and their laboratories, including Bob and Janet Siliciano, Mathias Lichterfeld and Xu Yu, Brad Jones, Florian Klein, Martin Tolstrup, Michel Nussenzweig, Marina Caskey, Daniel Kaufmann, Michael Seaman, and Christian Gaebler. https://lnkd.in/eVyhyQdT