IDI was established in 2002 in Kampala, Uganda by the Academic Alliance for AIDS Care and Prevention in Africa, a group of infectious diseases experts from Uganda and North America, with initial support from Pfizer Inc. and other partners.  This public-private partnership aimed to provide excellent care for People Living with HIV (PLHIV) in Uganda, to train healthcare workers to serve the tens of millions of PLHIV in Africa, to maintain the strategic emphasis on prevention, and to conduct research relevant to improving the outcome of the epidemic.In 2004, ownership of the Institute was transferred to Makerere University, and the Institute moved into its current building (pictured right).When the College of Health Sciences came into being at Makerere University in 2009, IDI became an integral part of the School of Medicine within the College while retaining its status as a not-for-profit organisation established within the University.  The IDI Board is chaired by the Professor Samuel Luboga Abimerech who is the Executive Director, Sustainable Leadership Institute and a retired Associate Professor at Makerere University.

IDI has developed strong and enduring links with the Ministry of Health (MoH) through its long term support of MoH facilities in the districts, Regional Referral Hospitals, and MoH headquarters functions; through its contribution to technical working groups; and through the key role played by the Institute in the national referral system.