Background: Antiretroviral therapy (ART) can maintain undetectable plasma HIV viraemia, but on stopping therapy HIV can be detected in the blood (‘viral rebound’), generally within a few weeks. For some individuals, the time to rebound may be protracted – up to months or years – and in some ‘post‐treatment controllers’ no rebound is reported.

Method: To explore the molecular differences between early and late rebounders, we present a longitudinal analysis of the host transcriptome that explores key genetic signatures associated with time to HIV rebound. We sequenced expressed host mRNA from South African women enrolled in the SPARTAC clinical trial, and who received treatment for up to 48 weeks, starting in primary infection. We studied CD4+ T‐cells sampled at ‘baseline’ before ART initiation and again at treatment interruption (wk 48). We used R and limma with voom to quantify and transform our data and Gene Set Enrichment Analysis software with the Reactome database to identify putative genetic signatures associated with clinical outcomes

Results: We find statistically significant enrichment of over 20 gene sets when comparing different ‘time to rebound’ phenotypes. We show that gene sets involved in the regulation of the immune response, in particular the Interferon Type I and the Immunoregulatory interactions between lymphoid and non‐lymphoid cells sets are up‐regulated in late versus early rebounders as well as rebounders versuslikely elite controllers. Notably, pre‐ and post‐ART samples seem to share pathway enrichment in the aforementioned gene sets.

Conclusion: These data suggest that specific components of the immune response may predict rapid rebound, post‐treatment control,and elite control and may help discovery of prognostic biomarkers for time to rebound and new interventions targeted at drug‐free HIV remission.