Spontaneous HIV expression during suppressive ART is associated with the magnitude and function of HIV-specific CD4+ and CD8+ T cells

• DOI: 10.1016/j.chom.2023.08.006
• Publication Date: 2023-09-13T14:36:54Z
• Authors: Mathieu Dubé; Olivier Tastet; Caroline Dufour; Gérémy Sannier; Nathalie Brassard; Gloria-Gabrielle ...; Amélie Pagliuzza; Corentin Richard; Manon Nayrac; Jean-Pierre Routy; Alexandre Prat; Jacob D. Estes; Rémi Fromentin; Nicolas Chomont; Daniel E. Kaufmann
• Keywords: Transcription

Spontaneous transcription and translation of HIV can persist during suppressive antiretroviral therapy (ART). The quantity, phenotype, biological relevance this spontaneously "active" reservoir remain unclear. Using multiplexed single-cell RNAflow-fluorescence in situ hybridization (FISH), we detect active 14/18 people with on ART, a median 28/million CD4+ T cells. While these cells predominantly exhibit abortive transcription, p24-expressing are evident 39% participants. Phenotypically diverse, reservoirs enriched central memory CCR6- activation-marker-expressing magnitude the positively correlates total HIV-specific CD8+ cell responses multiple clusters identified by unsupervised analysis. These associations particularly strong Single-cell vDNA sequencing shows that largely dominated defective proviruses. Our data suggest maintain ART.