HIV-1 dynamics in vivo: implications for therapy

Human immunodeficiency virus type 1 (HIV-1) replicates to high levels through all stages of infection, resulting in a progressive depletion of CD4+ T lymphocytes. Highly active antiretroviral therapy (HAART) has led to a significant reduction of HIV-1-related morbidity and mortality.Therapeutic interventions that are aimed at perturbing the equilibrium between HIV-1 production and clearance rates have helped to elucidate the dynamic nature of HIV-1 replication in vivo.Over the past eight years, minimal estimates for the turnover rates of virions and infected cell populations have been refined. The half-life of productively infected CD4+ T lymphocytes is approximately 17 hours; the turnover rate of virions is even faster, with a half-life of less than one hour. In an untreated, chronically infected individual with an average plasma viraemia (for example, 104–105 HIV-1 RNA copies ml−1), more than 10 billion virions are produced and cleared daily.Although most free virions are generated by short-lived productively infected CD4+ T lymphocytes, a small proportion (1–7%) originates from several longer-lived infected cell populations (for example, macrophages, resting T lymphocytes, follicular dendritic cells).HAART suppresses viral replication but fails to completely eliminate HIV-1 from an infected individual. Latently infected memory CD4+ T lymphocytes constitute a stable reservoir from which replication competent HIV-1 can emerge even after prolonged, seemingly suppressive, HAART. The half-life of this reservoir is long (6–44 months).Another important obstacle towards eliminating HIV-1 is the persistence of ongoing, low-level viral replication, even in cases with complete suppression of plasma viraemia during HAART.