Pilot Award

Despite the success of highly active antiretroviral therapy (HAART), many HIV-infected patients never achieve a CD4 recovery greater than 500 cells/mm3 even after many years on treatment. Poor immune reconstitution, despite good virologic control, is associated with low baseline CD4 count, old age, and co-morbid disease. While a number of interventions have been suggested to improve immunologic outcomes for those at risk for incomplete CD4 T cell response, very few have successfully improved outcomes for patients with poor initial immune recovery. Despite research to suggest that metformin has anti-inflammatory effects, its potential to modify immune activation and CD4 recovery in HIV-infected individuals has not been previously explored. Using prospective data from the Veterans Aging Cohort Study, the purpose of this study is to determine whether individuals with prevalent type 2 diabetes mellitus (T2DM) on metformin therapy have improved immune recovery in the first year after initiating HAART compared to individuals with prevalent diabetes not on metformin. Specifically, we propose to address the question of whether metformin has a role as adjunctive therapy in HIV therapy by assessing whether HIV-infected patients with concomitant T2DM have improved immunologic outcomes after initiation of metformin. Given the significant knowledge deficit in this area and the need for alternative strategies to improve immune function, the results of this analysis may provide invaluable insights into the mechanism of immune recovery and lead to further research exploring a broader role for metformin in HIV-infected adults.