M-PACT

Markers of Persistent immune ACTivation on Antiretroviral therapy in Africa

Objective

Aim
– To study the role and consequences of persistent immune activation/dysregulation in HIV-infected patients receiving suppressive antiretroviral therapy (ART) in sub-Saharan Africa.

Specific objectives
– To investigate the effects of hepatitis B and tuberculosis co-infections and HIV-1 subtypes on pre-cART and on-cART soluble immune biomarkers, CD4+ T-cell recovery and clinical outcomes
– To assess the effect of different cART regimens on soluble immune biomarkers.
– To explore the utility of microRNAs as novel prognostic biomarkers of immune recovery during ART.

Background

Recent scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has transformed HIV from a lethal to a chronic disease. Studies in high-income settings have shown that HIV-induced residual immune activation during ART is associated with poor immune recovery, AIDS and non-AIDS morbidity, and mortality. However, little is known about its health impact in Africa. We hypothesize that residual immune activation/dysfunction is greatly exacerbated in Africa, because of advanced pre-ART immunodeficiency, highly prevalent chronic co-infections (hepatitis B, tuberculosis, o.a.), and faster disease progression in HIV-1 subtype C infections. With millions of Africans accessing chronic care, residual immune activation poses a potential threat to effective life-long ART. This project will explore the effect of immune activation on treatment outcomes as well as novel biomarkers of immune recovery. Such knowledge will be crucial in the development of future adjunctive interventions to curb any detrimental effects of residual inflammation. MicroRNAs present an exciting novel opportunity as potential biomarkers of immune activation and recovery. The research project will be leveraged by the established PASER-M cohort in 5 African countries.

Summary

Name: M-PACT
Status: Start: Februari, 2015
End: January, 2018
Principal Investigator: Raph L. Hamers
Departments(s): AIGHD
Partners: Academic Medical Center of the University of Amsterdam (AMC), Dept. of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam, The Netherlands

Academic Medical Center of the University of Amsterdam (AMC), Dept. of Experimental Immunology (EXIM), Amsterdam, The Netherlands

University of Pretoria, Dept. of Immunology (UP-IM), Pretoria, South Africa

Contact information: Raph Hamers (r.hamers@aighd.org)
Stefanie Kroeze (s.kroeze@aighd.org)
Marloes Nijboer (m.nijboer@aighd.org)
Duration: Initiated
Funded by: Netherlands Organization for Scientific Research through the Innovational Research Incentives Scheme Veni (grant 91615036)
Countries: Nigeria, Kenia, South Africa, Zambia, Uganda
Publications: