REDUCE Study

Study Title: The Role of Undiagnosed Opportunistic Infections in Early Mortality among HIV-infected Patients Starting Antiretroviral Therapy in Africa (REDUCe Study)
Study Personnel:       International Principle Investigator (PI): Dr. Geng Elvin
Ugandan Principle Investigator   (PI):  Dr. Conrad Muzoora
Coordinator   :  Emmanuel B. Byaruhanga
Sponsor:  NIH
Study Site: Mbarara (ISS Clinic)

Introduction and Aims
Millions of HIV-infected patients are starting life-saving antiretroviral therapy in sub-Saharan Africa. However, the rate of mortality during first 3-6 months of treatment is high and not well explained. We hypothesize that these early deaths are due to opportunistic infections (OI’s) present but undiagnosed at the time of antiretroviral treatment initiation. These opportunistic infections are unlikely to improve on antiretroviral medications alone, which may even hasten mortality through the immune reconstitution inflammatory syndrome (IRIS). This proposal seeks to conduct a pilot study to identify whether early mortality may be due to unrecognized OI’s in a clinic-based cohort in Mbarara, Uganda. Therefore, we propose the following specific aims:

To determine the feasibility of collecting and storing peripheral blood and induced sputum on a consecutive sample of 300 patients starting antiretroviral therapy in Uganda and to later evaluate selected samples for the presence of underlying infections with Mycobacterium tuberculosis, Pneumocystis jirovecii, Cryptococcus neoformans, cytomegalovirus, Bartonella spp., HHV-8 and Histoplasma capsulatum .
To determine all deaths which occur within three months after starting antiretroviral therapy in this sample by adapting an existing patient-tracking protocol.

To estimate preliminary associations between deaths in the first three months on antiretroviral therapy and presence of underlying infections in stored samples.

Study design: Nest case-control study
Target enrollment number: 300