Although treatment with combination antiretroviral therapy leads to a reduction in the level of plasma viremia and an improvement in CD4 T cell count for most patients, for a minority of patients, an improvement in CD4 T cell count occurs despite the failure of treatment to suppress viral replication. Recent reports suggest that these discordant improvements in CD4 T cell count may last for months to years and are associated with improved clinical outcomes. In a retrospective observational study, we evaluated the effect of therapy cessation on 8 patients with discordant immunologic responses to therapy and found that improved CD4 T cell responses are dependent upon ongoing drug pressure. If antiretroviral agents that are likely to resuppress the virus are not available, we suggest that patients continue the therapy associated with immunologic improvement to maximize the clinical benefit of the discordant response.