Most patients starting highly active antiretroviral therapy (HAART) show suppression of HIV replication below the level of detection (currently <50 HIV-1 RNA copies/mL in most assays), and experience a gradual rise in CD4 lymphocyte count, which may continue for several years. The CD4 count response is generally related to the degree of viral load suppression, and this typical pattern of CD4 and viral load response is associated with a marked improvement in prognosis. In some patients, however, there is discordance in the response. Either there is suppression of viral load but poor recovery of immune function, characterized by little or no CD4 cell count increase or, conversely, an improvement in CD4 cell count with incomplete or delayed viral load suppression. Little is known about the pathogenesis of discordant responses, which seems to depend on the interaction of a multitude of viral, host and treatment-related factors. Available evidence indicates that discordant responses are associated with an intermediate risk of death or clinical progression. At present, recommendations for the clinical management of patients with discordant responses to antiretroviral therapy are largely based on observational, uncontrolled data. The development of standardized and universally accepted definitions of discordant responses is necessary to allow meaningful comparisons between studies to be made, as well as to help in the design of trials of possible therapeutic interventions.
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