title: The Clinical Implications of Reduced Viral Fitness.
abstract: Viral fitness, defined as the extent of viral adaptation to the host environment, arises from tissue tropism, immune system evasion, drug resistance, and viral replication capacity. The fitness of wild-type and drug-resistant HIV-1 varies widely, associating with plasma viremia, CD4+ T-cell count, and clinical progression. HIV-1 fitness may be measured in competitive culture assays, single cycle assays, or single cycle assays based on a subgenomic fragment of HIV-1, which has been standardized as the replication capacity assay (pol RC). During virologic failure of antiretroviral therapy, CD4 T-cell counts remain elevated while pol RC declines and remains durably lower because of drug-selected changes in the gag and pol genes. CD4 T-cell sparing also is observed among patients without evidence of drug resistance who carry a low pol RC virus. Reduced HIV-1 replication capacity and virulence may occur because of drug resistance or viral escape from host immune responses.
authors.affiliation: Gladstone Institute of Virology and Immunology, PO Box 419100, San Francisco, CA 94141, USA. rgrant@itsa.ucsf.edu
authors.forename: Jason D.
authors.initials: JD
authors.lastname: Barbour
authors.forename: Robert M.
authors.initials: RM
authors.lastname: Grant