M-PACT

New challenge for HIV in Africa; exacerbated immune activation during antiretroviral treatment; biomarkers and health impact

Many coloured medicines of different types

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.


Description

A 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 five African countries.


AIGHD Research Lead

Raph Hamers


Partners

  • Academic Medical Center of the University of Amsterdam (AMC), Dept. of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam, Netherlands
  • Academic Medical Center of the University of Amsterdam (AMC), Dept. of Experimental Immunology (EXIM), Amsterdam, Netherlands
  • University of Pretoria, Dept. of Immunology, Pretoria, South Africa and local partners:
    • Joint Clinical Research Centre, Uganda
    • Lagos University Teaching hospital, Nigeria
    • Coast Province General Hospital, International Centre for Reproductive Health, Kenya
    • Muelmed Hospital, Pretoria, South Africa. 5. Lusaka Trust Hospital, Lusaka, Zambia

Funders

Netherlands Organization for Scientific Research through the Innovational Research Incentives Scheme Veni (grant 91615036)


Countries

Nigeria

Kenya

South Africa

Zambia

Uganda