Development of a natural drug 'mimic' derived from dendritic cells that activate latent HIV-1 and potentially could cure infected patients

Development of a natural drug 'mimic' derived from dendritic cells that activate latent HIV-1 and potentially could cure infected patients

Project

HIV-1 can infect cells from the immune system without producing new viruses. These cells form a life-long existing viral reservoir that can not be eradicated with the current therapy. Spontaneuos virus activation of this latent HIV-1 reservoir neccesitates constant use of medication to actively suppress virus replication. This reservoir could be eradicated from pateints, if a drug is available that could activate latent HIV-1, while virus dissemmination is controlled with HAART. However, despite masive effort no effective anti-latency drug or compound is developed. We have identified a natural protein derived from dendritic cells that can activate latent HIV-1. In this project we aim to design and produce a mimic of that protein to ultimately eradicate the latent viral reservoir in patients.

Project details

Time frame
30 September 2017 - 31 August 2018
Budget
€ 75,000
Active in
Netherlands

Objectives

This project aims to find an effective LRA to reduce the latent HIV-1 reservoir. Current therapy in the form of HAART is effective in blocking HIV-1 replication. Treatment, however, cannot eradicate the latent HIV-1 reservoir formed in the early acute and chronic infection phase of disease progression. Eradication of the latent reservoir with an LRA combined with therapy could possibly result in cure from HIV-1. If the dLRA investigated in this project has an effect on the size of the latent reservoir, patients could be cured or the use of medication could be reduced.

Community groups

The nature of this project is fundamental research. Neverthess, those that are infected with HIV-1 could benefit by the finding. All HIV-1 infected individuals that are on successful therapy could use the dLRA to reduce their latent viral reservoir.

Background

Currently developed LRAs are PKC pathway inducers, HDAC inhibitors or PTEN modulators. Some of these LRAs activate the virus in latently infected cells or cell lines, but treatment of patients with these LRAs does not have a positive effect on reduction of the latent viral reservoir. Dendritic cells are able to secrete a natural dLRA that reverts HIV-1 latency by other means. The activity of the dLRA is not dependent on PKC activation or the chromatin acetylation state as induced by HDAC inhibitors. With mass spectrometry and antibody depletion experiments we have identified the soluble dLRA derived from dendritic cells.

Treatment of HIV-1 infected patients with HAART effectively blocks virus replication, but viral reservoirs that contain latent HIV-1 are not eradicated. Spontaneous activation of virus replication from this latent reservoir can occur, which necessitates life-long adherence of therapy. Therapy adherence has to be strong, while side effects and costs are high for patients. Especially in developing countries accessibility of life-long therapy and high medicine cost render successful therapy an enormous challenge. Eradicating latent viral reservoirs with a powerful LRA in combination with therapy could lead to a functional or complete cure, which would reduce the discomforts of patients.

Goals

A cure for HIV
100%
Contributed within this project

Partners

Other projects within the programme

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 major obstacle to an HIV cure is the presence of a persistent viral reservoi...

A costimulatory power-boost for HIV-specific T-cells through GITR activation

People infected with HIV have nowadays almost the average life expectancy of the...

2016 RfP - Scientific Research High Risk, High Gain

This project is part of 2016 RfP - Scientific Research High Risk, High Gain

Aidsfonds.org uses cookies to offer the best website experience possible and to anonymously analyze website behaviour. More information.