- Collins, David R;
- Urbach, Jonathan M;
- Racenet, Zachary J;
- Arshad, Umar;
- Power, Karen A;
- Newman, Ruchi M;
- Mylvaganam, Geetha H;
- Ly, Ngoc L;
- Lian, Xiaodong;
- Rull, Anna;
- Rassadkina, Yelizaveta;
- Yanez, Adrienne G;
- Peluso, Michael J;
- Deeks, Steven G;
- Vidal, Francesc;
- Lichterfeld, Mathias;
- Yu, Xu G;
- Gaiha, Gaurav D;
- Allen, Todd M;
- Walker, Bruce D
Spontaneous control of HIV infection has been repeatedly linked to antiviral CD8+ T cells but is not always permanent. To address mechanisms of durable and aborted control of viremia, we evaluated immunologic and virologic parameters longitudinally among 34 HIV-infected subjects with differential outcomes. Despite sustained recognition of autologous virus, HIV-specific proliferative and cytolytic T cell effector functions became selectively and intrinsically impaired prior to aborted control. Longitudinal transcriptomic profiling of functionally impaired HIV-specific CD8+ T cells revealed altered expression of genes related to activation, cytokine-mediated signaling, and cell cycle regulation, including increased expression of the antiproliferative transcription factor KLF2 but not of genes associated with canonical exhaustion. Lymphoid HIV-specific CD8+ T cells also exhibited poor functionality during aborted control relative to durable control. Our results identify selective functional impairment of HIV-specific CD8+ T cells as prognostic of impending aborted HIV control, with implications for clinical monitoring and immunotherapeutic strategies.