Trial ASsociation of Two pathogens - In vitro (TAST-I) version 3
Research type
Research Study
Full title
Trial ASsociation of Two pathogens - In vitro: Linking HIV clade with Mycobacterium tuberculosis virulence in vitro
IRAS ID
77882
Contact name
Francis Drobniewski
Contact email
Sponsor organisation
Barts Health NHS Trust
Research summary
TAST-I:
This study will investigate the mechanisms by which two human pathogens, Human Immunodeficiency Virus (HIV) and Mycobacterium tuberculosis (MTB), interact at the cellular and molecular levels. TAST-I has been designed to increase knowledge on the host immune response towards MTB in HIV-infected individuals.
This is of high importance since HIV-positive individuals are more likely to either become infected with MTB, or “re-activate“ (when already carrying MTB) and subsequently develop tuberculosis (TB), than HIV-negative individuals are. Additionally, TB treatments prove less effective in HIV-positive than in HIV-negative individuals and TB now accounts for over one-third of all acquired immunodeficiency syndrome (AIDS)-related deaths. TAST-I will help us to identify molecules and cells that render HIV-infected individuals highly susceptible to MTB infections.
Target cells (macrophages) derived from HIV+ donors will be infected, in vitro, with different types of MTB (strains) that have epidemiological relevance to the human population. Subsequently, infected macrophages and whole blood will be used to run immunological assays whose readouts are predictors of successful pathogen containment in vivo. Soluble factors and cell surface molecules, markers of both the innate and acquired immunity response to MTB, will be measured. Growth of MTB within macrophages will be quantified. The effects of HIV type (clade) onto all readouts, and of vitamin D onto some readouts, will be assessed.
We have secured money from the Barts and the London Charity (BTLC) to cover for the cost of the study including the recruitment of 80 HIV-infected individuals regularly attending the Grahame Hayton Unit (GHU) at the Royal London Hospital. Informed consent will be sought and volunteers asked for 11 desert spoonfuls of their blood on one occasion concomitant to their routine visit to the GHU. 20 HIV-negative individuals will also be recruited and their blood use as a “benchmark“.REC name
London - Riverside Research Ethics Committee
REC reference
13/LO/0946
Date of REC Opinion
12 Jul 2013
REC opinion
Favourable Opinion