Inducible Viral Reservoir Assessment; at the Intersection of Innovative Strategies Towards HIV Cure

Research output: Types of ThesisDoctoral ThesisInternal

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Abstract

Approximately 40 million people live with HIV-1 (PLWH) globally (UNAIDS 2023).Modern, highly suppressive antiretroviral therapy (ART) effectively blocks viral replication to below detection limits and has significantly curbed HIV-1 transmission and improved health outcomes for many people with access to ART (~75 % of global population of PLWH) (UNAIDS 2023). However, ART is not curative and must be taken lifelong, posing considerable socio-economic burdens, particularly in resource-limited, high HIV-burdened settings. Moreover, people with HIV-1 on long-term ART have increased risk for comorbidities consequent to persistence of HIV-1 in blood and tissues (HIV-1 reservoirs), chronic inflammation, accelerated aging and ART toxicity. Hence, multiple strategies are currently pursued in global scientific efforts to achieve ART-free control and thereby improve overall long-term health outcomes of PLWH.
As novel HIV-1 therapeutic trials continue advancing, there is a critical need for standardized, clinically validated HIV-1 reservoir assays to evaluate intervention efficacy. Established and emerging HIV-1 reservoir assays require rigorous evaluation of performance characteristics (sensitivity, specificity, reproducibility, scalability) and their relationship to the outcomes of pre-clinical and clinical HIV-1 cure studies. These studies are imperative to address key questions, which are critical to the evaluation of therapeutic interventions toward HIV-1 cure. Given the multifaceted nature of HIV-1 persistence, what molecular compartments of the latent HIV-1 reservoir should be prioritized (DNA, RNA, protein, virus?) and what tools should be used to monitor changes in these molecular compartments? Furthermore, in context of a putative HIV-1 cure intervention, when should we sample to monitor changes in the latent HIV-1 reservoir and how frequently should we monitor? What is the short and long-term impact of an intervention on different molecular compartments of the HIV-1 reservoir, and which of these measures of persistence are clinically significant? The research described in this thesis aims to address these critical questions surrounding the evaluation of novel putative strategies towards HIV-1 cure or ART-free viral control.

Original languageEnglish
Awarding Institution
  • Erasmus University Rotterdam
Supervisors/Advisors
  • Mahmoudi, Tokameh, Supervisor
  • Boucher, Charles, Supervisor
  • Gruters, Rob, Co-supervisor
Award date1 May 2024
Place of PublicationRotterdam
Print ISBNs978-94-6483-979-1
Publication statusPublished - 1 May 2024

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