Non-invasive plasma glycomic and metabolic biomarkers of post-treatment control of HIV

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.

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling

“…Metabolomics analysis was performed as described previously ( 145 , 146 ). Briefly, polar metabolites were extracted with 80% methanol.…”

Preliminary Acceptability of a Home-Based Peripheral Blood Collection Device for Viral Load Testing in the Context of Analytical Treatment Interruptions in HIV Cure Trials: Results from a Nationwide Survey in the United States

“…In these investigations, people with HIV (PWH) interrupt antiretroviral treatment (ART) to test whether experimental interventions can keep HIV suppressed in the absence of therapy. Despite ongoing research [3][4][5], there is currently no biomarker available that can accurately predict when virus will return for a given participant. Frequent viral load testing during ATIs is necessary to detect viral rebound and determine when participants must restart ART [1].…”

Viral and Host Biomarkers of HIV Remission Post Treatment Interruption

“…Given the complexity of this measurement, its associations with TTVR or viral remission have not been evaluated frequently. However, one recent study found that lower levels of defective and hypermutated, but not intact, HIV DNA associated with delayed viral rebound [25]. In the same study, the lower levels of intact, defective, and hypermutated HIV DNA were associated with a higher likelihood of achieving a PTC phenotype after ATI [25].…”

“…As a consequence, these assays overestimate the size of replication-competent reservoirs. Despite this limitation, the pre-ATI levels of total HIV DNA have been associated with TTVR [12,24,25] as well as with post-treatment control [26,11,27,25,28,29]. However, such associations have not been consistent.…”

“…However, one recent study found that lower levels of defective and hypermutated, but not intact, HIV DNA associated with delayed viral rebound [25]. In the same study, the lower levels of intact, defective, and hypermutated HIV DNA were associated with a higher likelihood of achieving a PTC phenotype after ATI [25]. The lack of observed correlation between intact HIV DNA (measured by sequencing) and TTVR could be explained by the lower values and dynamic range of intact HIV DNA levels (compared to defective and hypermutated HIV DNA levels).…”