PMID: 8595501Jan 1, 1995Paper

AIDS pathogenesis: from models to viral dynamics in patients

Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association
M A Nowak

Abstract

The course of HIV infection usually follows a pattern in which the immune system is initially able to limit viral replication, but ultimately fails. It is proposed that disease progression is a consequence of viral replication and evolution within the host, the immune response providing the selection pressure for increasing diversity. When the number of mutants rises above a certain threshold level, the immune system can no longer downregulate all the viral variants simultaneously and symptomatic disease results. Recent studies of the dynamics and kinetics of HIV infection have indicated that 30% of the free virus population in the plasma is replenished each day, a very high turnover rate. After intervention with nevirapine, resistant virus was observed to have replaced wild-type virus in the plasma within 2-4 weeks. Even in late-stage patients, the immune system has the capacity to regenerate large numbers of CD4 cells, but this ability does not continue indefinitely. This implies that to reverse immunodeficiency the principal objective of treatment in the management of HIV infection should be inhibition of viral replication and thus prevention of lymphocyte destruction.

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