The FIND study: core-needle biopsies to detect the hidden HIV reservoirs in hard-to-reach tissue compartments of well-controlled and uncontrolled HIV-patients

The FIND study: core-needle biopsies to detect the hidden HIV reservoirs in hard-to-reach tissue compartments of well-controlled and uncontrolled HIV-patients

Project

The major obstacle to an HIV cure is the presence of a persistent viral reservoir of latently-infected cells. Yet many basic questions about the location and composition of viral reservoirs remain unanswered. In this study we will determine whether minimally-invasive fine-needle biopsies can be used to investigate the viral reservoirs in hard-to-reach tissue compartments of HIV infected patients within hours of death. Ten HIV-infected patients (5 on ART) will be enrolled, and multiple fine-needle biopsies on 15 target organs will be performed. HIV-DNA will be quantified and the viral population will be characterized. The outcome of this study will provide novel insights into HIV reservoirs and reservoir dynamics in response to ART, and will help to target future HIV eradication strategies.

Project details

Time frame
14 September 2017 - 31 May 2019
Budget
€ 73,511
Active in
Netherlands

Objectives

This study is designed to test the feasibility of investigating the HIV reservoir via post-mortem fine-needle biopsies. If the approach is successful and sufficient levels of viral DNA can be detected, in-depth viral and cellular characterization can be performed. This will provide insight into the presence and dynamics of the persisting viral reservoirs despite successful antiretroviral therapy, which will be extremely relevant for eradication studies.
The study-specific outcomes include: 1) the feasibility of the fine-needle approach to analysing the size and cellular composition of remaining reservoirs, 2) the quantification of HIV DNA in these cellular reservoirs, and 3) sample repository.

Community groups

No patients will be directly affected by this study.

Background

Isolated cases of an HIV cure (Berlin Patient) and the short- and long-term control of HIV infection (Mississippi baby, Boston patients, Visconti cohort) have galvanized the HIV research community into trying to gain a better understanding of persistent HIV reservoirs. The different viral reservoirs all represent their own unique microenvironment affected by localized immune pressures, cell type-specific differences in replication and cell/tissue-specific penetration of antiretroviral drugs and/or selection of drug resistance. Since these viral reservoirs represent the major obstacle to viral eradication and are difficult if not impossible to sample while patients are alive, we propose a rapid in-depth post-mortem analysis using minimally-invasive fine-needle biopsies.

Remarkably few autopsy studies of the HIV reservoir have been conducted in the ART-era. Our team in the Netherlands and South Africa has experience in several post-mortem studies. Full autopsies were performed within the European Stem Cell transplantation program (EpiStem). However, these studies were notoriously difficult to conduct since only a few patients/families provided their consent. In contrast, a study conducted by our research team (as proposed for this research call) in South Africa acquired consent from half of the approached patients/families for minimally-invasive ultrasound-guided fine-needle biopsies, as well as limited lymph node and skin excisions.

Goals

A cure for HIV
100%
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