HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy.
Several recent reports indicate that the long, clinically latent phase that characterizes human immunodeficiency virus (HIV) infection of humans is not a period of viral inactivity, but an active process in which cells are being infected and dying at a high rate and in large numbers. These results lead to a simple steady-state model in which infection, cell death, and cell replacement are in balance, and imply that the unique feature of HIV is the extraordinarily large number of replication cycles that occur during infection of a single individual. This turnover drives both the pathogenic process and (even more than mutation rate) the development of genetic variation. This variation includes the inevitable and, in principle, predictable accumulation of mutations such as those conferring resistance to antiviral drugs whose presence before therapy must be considered in the design of therapeutic strategies.
Coffin
J M
JM
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111.
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D016923:Cell Death; D004279:DNA, Viral / Q000097:blood; D004352:Drug Resistance, Microbial; D014644:Genetic Variation; D006678:HIV / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D006801:Humans; D007700:Kinetics; D009154:Mutation; D011533:Proviruses / Q000235:genetics / Q000502:physiology; D012367:RNA, Viral / Q000097:blood; D014766:Viremia / Q000821:virology; D014779:Virus Replication
D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral