title: Selective inhibition of syncytium-inducing and nonsyncytium-inducing HIV-1 variants in individuals receiving didanosine or zidovudine, respectively.
abstract: By studying changes in the clonal composition of HIV-1 populations during the first weeks of zidovudine (ZDV) treatment before the development of ZDV resistance-conferring mutations, we demonstrated previously a selective inhibition of nonsyncytium-inducing (NSI) HIV-1, even when present as coexisting population in individuals also harboring syncytium-inducing (SI) HIV-1. In this study, we observed the opposite in individuals receiving didanosine (ddI) treatment. In these individuals (n = 7) a median -0.98 log change (range -1.55-0.08) in infectious cellular SI load was observed, whereas the coexisting NSI load was only minimally affected (median -0.15 log, range -1.27-0.50; P = 0.03). The virus phenotype-dependent treatment responses were independent of the clonal composition of HIV-1 populations at baseline. Individuals treated with a combination of ZDV and ddI revealed an equal decline of both NSI and SI infectious cellular load (n = 4; NSI: median -1.55 log, range -2.19 to -1.45; SI: median -1.47 log, range -1.81 to -0.86; P = 0.56). To test the hypothesis that the previously reported optimal activation of ZDV and ddI in activated and resting T cells, respectively, in combination with the differential T cell tropism of NSI and SI HIV-1 is the basis for the observed virus phenotype specific efficacy of nucleoside analogs, we studied the effect of treatment with a protease inhibitor that does not require intracellular activation. Individuals receiving ritonavir (n = 4) indeed showed equal declines in NSI and SI infectious cellular load (NSI: median -2.37 log, range -2.59 to -2.16; SI: median -2.82 log, range -3.14 to -2.50; P = 0.25). Our data suggest HIV-1 phenotype as an additional parameter in the design of optimal treatment regimens.
authors.affiliation: Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, The Netherlands.
authors.forename: A B
authors.initials: AB
authors.lastname: van't Wout
authors.forename: L J
authors.initials: LJ
authors.lastname: Ran
authors.forename: M D
authors.initials: MD
authors.lastname: de Jong
authors.forename: M
authors.initials: M
authors.lastname: Bakker
authors.forename: R
authors.initials: R
authors.lastname: van Leeuwen
authors.forename: D W
authors.initials: DW
authors.lastname: Notermans
authors.forename: A E
authors.initials: AE
authors.lastname: Loeliger
authors.forename: F
authors.initials: F
authors.lastname: de Wolf
authors.forename: S A
authors.initials: SA
authors.lastname: Danner
authors.forename: P
authors.initials: P
authors.lastname: Reiss
authors.forename: C A
authors.initials: CA
authors.lastname: Boucher
authors.forename: J M
authors.initials: JM
authors.lastname: Lange
authors.forename: H
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count / Q000187:drug effects; D002459:Cell Fusion / Q000187:drug effects; D016049:Didanosine / Q000494:pharmacology / Q000627:therapeutic use*; D015726:Giant Cells / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D051379:Mice; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D015215:Zidovudine; D016049:Didanosine; D019438:Ritonavir