Research on HIV latency in the viral reservoir

Research on HIV latency in the viral reservoir

Project

Dr. Monique Nijhuis aims to characterize the latently HIV-infected viral reservoir in patients: How big is it, what is its composition and does the reservoir change during long-term antiretroviral therapy? Nijhuis also aims to determine the re-activation level required for the immune system to be able to recognise and eradicate these HIV-infected cells.

Project details

Time frame
15 February 2014 - 14 August 2018
Budget
€ 248,115
Active in
Netherlands

Objectives

This project aims to analyse size, characteristics and re-activation potential of the latently infected T-cell subsets and to obtain quantitative insights in the longevity of these subsets in vivo.
Highly-sensitive, digital-PCR technology will be combined with deep-sequence analysis to investigate size, composition and evolution of the viral reservoir in longitudinal plasma, PBMC and T-cell subsets in the same patients over 15 years of effective therapy. Characteristics of the PBMC and T-cell subsets will also be analyzed and related to their average in vivo life-span (D2O labeling) and their in vitro reactivation potential in a novel latency model.
Aim 1) Identify and quantify the HIV reservoir in T-cell subsets over 15 years of effective cART.
Aim 2) Determine the characteristics of the different T-cell subsets with respect to longevity, immunological markers and viral quasispecies over time.
Aim 3) Determine the reactivation potential of the latently infected T-cell subsets over time.
Output: scientific publications

This study uses unique patient material and highly innovative techniques, never before employed in parallel, to characterize the HIV reservoir, opening a door to HIV eradication.

Community groups

scientific community

Background

Many people live with HIV, but there is currently no cure. Presence of a stable reservoir of HIV-infected cells prevents eradication with contemporary treatment strategies. Targeting and eliminating these cells is essential for eradication, yet many basic questions about the composition of the latent reservoir remain unanswered.

To date, the only proven cellular HIV reservoir during long-term treatment is the CD4+ T-cell. This cell population is highly heterogeneous and includes several distinct subsets with specific characteristics that may substantially impact the long-term in vivo persistence and re-activation potential. However, little is known about the characteristics and re-activation potential of these latently infected cells.

Goals

A cure for HIV
100%
Contributed within this project

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