Highly active antiretroviral therapy successfully suppresses viral replication and increases CD4+ T cell counts in most patients with HIV infection. However, there is a group of patients which exhibits discordant treatment responses, with poor CD4 reconstitution despite successful viral suppression. The clinical consequences of such immunological failure are significant, including both AIDS-related and non-AIDS-related pathology, yet the group is poorly characterised. Little is known about why certain patients do not gain the full benefit of HAART, and there are consequently few therapeutic options currently available to improve their care.To investigate relevant aspects of the immunopathology of HIV infection in patients on HAART, we have 124 selected patients with persistent viral suppression after 3-9 months of HAART and degrees of CD4 reconstitution ranging from no gains at all to normal CD4 levels. A range of soluble markers of inflammation and apoptosis will be quantified by ELISA technique, in serum samples from each patient from before HAART initiation, and at 6, 12, 24 and 36 months of HAART. We will seek correlates between rates of CD4 gain and measured levels of cytokines and soluble membrane proteins, during the first 36 months of HAART. Hopefully, the discovery of such relationships may further elucidate the mechanisms underlying discordant treatment responses in HIV patients, and contribute to improved disease management.