Basic Science Programme / DART Immunology Substudy Project

Lead Research Organisation: MRC/UVRI Uganda Research Unit on AIDS

Abstract

It has been suggested that patients who achieve viral suppression due to antiretroviral treatment (ART) may differ with regards to the type and quality of the immune response to HIV that they are able to regain after some time on ART, depending on whether they are treated continuously or undergo structured treatment interruptions (STIs). It has also been proposed that the immune system of a patient may achieve a higher level of competence if HIV is not totally suppressed. The DART trial provided an opportunity to study this question: This trial has a study component aiming to investigate the clinical effectiveness of STIs as compared to that of continuous treatment (CT). Whilst this component of the DART Trial was terminated early in 2006 because CT showed better clinical results than STI, the immunological research component continues using specimens obtained from patients who formerly participated in this trial component.

Technical Summary

Purpose: To compare the HIV-specific immune reconstitution following exposure to antiretroviral therapy (ART) in patients who received ART through structured treatment interruption (STI) with that in participants who received continuous treatment (CT). This research will allow to establish whether the immune system of a patient on ART may achieve a higher level of competence if HIV is not totally suppressed.||Methods: Study participants were recruited from the DART Trial study clinic in Entebbe (see separate abstract). A sub-group of patients of this trial were randomized to either STI or CT once their immune status has substantially approved. At baseline, before patients started ART, HIV-induced CD8 perforin and interferon gamma (IFN- ) release to vpu, vpr, tat, rev, vif, and nef HIV peptide pools was evaluated. Staphylococcal enterotoxin B (SEB) were used for positive control tests while unstimulated specimens were used to evaluate pre-existing cytokine release. Subsequently, immune responses are evaluated at three-monthly intervals using intracellular cytokine staining assay. Immune responses were correlated with viral load, CD4 counts and clinical observations and compared between individuals on STI and on CT.

Publications

10 25 50
 
Description Lack of benefit of structured treatment on immune response
Geographic Reach Multiple continents/international 
Policy Influence Type Gave evidence to a government review
Impact The interruption of ARV treatment in HIV patients is not encouraged
 
Description Dart immunology substudy 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Our team has processed the samples and performed the immunological assays
Collaborator Contribution Training other capacity building and publications
Impact A paper was published