Why is antiretroviral therapy not always effective?

Why is antiretroviral therapy not always effective?

Project

Current antiretroviral therapy is a giant improvement compared with previous treatments. Nevertheless, statistics show that for one quarter of HIV treatment patients, the immune system does not recover. AMC researcher, Aleksander Pasternak, aims to identify why these patients’ blood viral load does not drop and their antibody levels do not return to normal. To do this, he will determine whether those patients who do not respond well to HIV treatment have any specific immune system disorders.

Project details

Time frame
10 February 2013 - 30 November 2019
Budget
€ 250,000
Active in
Netherlands

Objectives

This research project will be the first to investigate in parallel a significant number of virological, immunological, and genetic factors in relation to IF. In particular, virus production and the size of viral reservoir will be assessed using our innovative seminested real-time PCR assays. Both a retrospective case-control study including significant numbers of patients, and a prospective study of patients followed from the start of ART will be performed. Taken together, these two studies will allow comparing different virus and host biomarkers between immunological responders and nonresponders, investigating the dynamics and mutual correlation of these biomarkers, and – most importantly – determining the predictive value of these biomarkers for IF.
The researchquestions are:
1. Does virus production in patients on ART correlate with IF?
2. Is IF associated with co-infection with other pathogens and microbial translocation?
3. Which of the aforementioned influences are mediated through increased T-cell activation and apoptosis?
4. Which other immunological biomarkers correlate with IF?
5. Does host genetics determine IF?
6. Does decreased thymic output influence IF?
7. Do the levels and longitudinal trends of immunological and virological biomarkers correlate with each other?
8. Which of the aforementioned host and viral factors are predictive for IF, in a prospectively followed patient cohort?

The ultimate goal of this research is personalized etiological diagnosis and treatment for every individual with an incomplete therapy response. This is of benefit of the individual patient but may also prevent transmission of HIV

Community groups

scientific community

Background

Current antiretroviral therapy is a giant improvement compared with previous treatments. Nevertheless, statistics show that for one quarter of HIV treatment patients, the immune system does not recover.

Suboptimal CD4+ T cell response is associated with increased AIDS- and non-AIDS-related morbidity and mortality. Notwithstanding such alarming proportions, there is still no efficient therapeutic strategy for such situations.

Goals

Everyone living with HIV worldwide receives treatment
100%
Contributed within this project

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