Abstract
Non-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed. Such biomarkers can improve the safety of analytic treatment interruption (ATI) and provide mechanistic insights into the host pathways involved in post-ART HIV control. Here we report plasma glycomic and metabolic signatures of time-to-viral-rebound and probability-of-viral-remission using samples from two independent cohorts. These samples include a large number of post-treatment controllers, a rare population demonstrating sustained virologic suppression after ART-cessation. These signatures remain significant after adjusting for key demographic and clinical confounders. We also report mechanistic links between some of these biomarkers and HIV latency reactivation and/or myeloid inflammation in vitro. Finally, machine learning algorithms, based on selected sets of these biomarkers, predict time-to-viral-rebound with 74% capacity and probability-of-viral-remission with 97.5% capacity. In summary, we report non-invasive plasma biomarkers, with potential functional significance, that predict both the duration and probability of HIV remission after treatment interruption.
Highlights
Non-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed
Because the impact of interventions on the total body burden of HIV cannot be measured with current technologies, HIV cure-focused clinical trials rely on an analytic treatment interruption (ATI) as the only definitive approach to evaluate the effectiveness of interventions[2]
The definition of posttreatment control was: remaining off ART for ≥24 weeks post-ATI with viral load (VL) ≤ 400 copies for at least 2/3 of time points; no ART in the plasma; and no evidence of spontaneous control preART
Summary
Non-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed Such biomarkers can improve the safety of analytic treatment interruption (ATI) and provide mechanistic insights into the host pathways involved in post-ART HIV control. We report plasma glycomic and metabolic signatures of time-toviral-rebound and probability-of-viral-remission using samples from two independent cohorts These samples include a large number of post-treatment controllers, a rare population demonstrating sustained virologic suppression after ART-cessation. These realities highlight the urgent need for biomarkers that can predict time-to-viralrebound after treatment interruption and can be leveraged to guide clinical decision making Such biomarkers could improve the safety of ATIs and accelerate the development of an HIV cure by providing a means for selecting only the most promising therapies for testing by ATIs3. Plasma metabolites are biologically active molecules that can regulate immunological responses, including inflammatory responses[20,21]
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