Plasma Glycomic Biomarkers for Non-Invasive HIV Rebound Prediction
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Solution Overview
Problem
Current technologies lack reliable biomarkers to predict the impact of interventions on HIV reservoirs, relying on costly and risky Analytical Treatment Interruption (ATI) to evaluate the effectiveness of HIV cure-focused clinical trials, and existing biomarkers fail to accurately measure the body's response to antiretroviral therapy (ART) interruption.
Innovation Solution
Development of a diagnostic kit and method using specific metabolites and glycans such as Plasma A3G3S3 glycans, Pyruvic acid, Total fucose, and L-glutamic acid to non-invasively predict time-to-viral rebound and probability of viral rebound after ART interruption, allowing for more accurate clinical decision-making and potentially guiding HIV cure strategies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Analytical Treatment Interruption (ATI) is used to evaluate the effectiveness of HIV cure-focused clinical trials, then definitive evaluation of intervention impact on HIV reservoir can be achieved, but the approach becomes costly, cumbersome, and poses risks to study participants and the community
Solution Approach 1:
The patent introduces plasma metabolites and glycans as intermediary biomarkers that mediate the evaluation of HIV reservoir impact. These biomarkers serve as indirect indicators that correlate with viral rebound risk, allowing researchers to assess intervention effectiveness without requiring treatment interruption. The biomarkers act as a bridge between the intervention and the desired outcome measurement, eliminating the need for ATI while maintaining evaluation reliability.
2Reliability
If Analytical Treatment Interruption (ATI) is used to determine intervention impact on HIV reservoir, then definitive evaluation can be achieved, but the approach becomes costly and time-consuming
Solution Approach 1:
The patent employs biomarker measurement during ongoing antiretroviral therapy as a preliminary assessment tool. By measuring plasma metabolites and glycans while the patient is still on treatment, the evaluation can be performed before treatment interruption occurs. This preliminary action allows researchers to predict viral rebound risk and assess intervention effectiveness continuously, eliminating the time loss associated with waiting for post-ATI viral rebound data.
3Measurement precision
If ATI is used as the only definitive approach to evaluate intervention effectiveness, then accurate assessment of viral reservoir impact can be obtained, but risks to study participants and the community increase
Solution Approach 1:
The patent implements continuous feedback monitoring of plasma biomarkers during antiretroviral therapy. By regularly measuring metabolite and glycan levels, the system provides ongoing feedback about the HIV reservoir status and viral rebound risk. This feedback mechanism allows for real-time assessment of intervention effectiveness without requiring treatment interruption, thereby eliminating the harmful risks associated with ATI while maintaining precise measurement capability.
4Reliability
If existing biomarkers such as exhaustion markers on CD4+ T cells or cell-associated HIV DNA and RNA are used, then some correlation with viral rebound can be obtained, but the correlations are generally weak and they fail as biomarkers when assessed during ART
Solution Approach 1:
The patent shifts the measurement parameter from cellular biomarkers (exhaustion markers, cell-associated HIV DNA/RNA) to plasma-based metabolomic and glycomic parameters. This parameter change enables biomarker assessment during ongoing antiretroviral therapy, as plasma metabolites and glycans can be measured non-invasively from blood samples without requiring treatment interruption. The new parameters maintain strong correlation with viral rebound while being adaptable for use during active treatment.
Data Source
AI summary
Methods and compositions are provided for the non-invasive diagnosis of likelihood of HIV remission after antiretroviral therapy (ART) interruption, prediction of time-to-viral-rebound in an HIV subject after ART interruption and prediction of the probability of viral rebound in an HIV subject after ART interruption. Methods for treating HIV subjects by increasing or decreasing expression of certain metabolites or glycans are also provided.