title: Evidence for predominance of CCR5-using HIV-1 strains during highly active antiretroviral therapy.
abstract: BACKGROUND
  Very little is known about the influence of Highly Active Antiretroviral Therapy (HAART) on the surface expression of CCR5 and CXCR4 with respect to receptor tropism and replication kinetics of autologous HIV strains, during continuous therapy and structured treatment interruption (STI) regimens.
  
  
  OBJECTIVE
  The main objectives of this study were to assess whether continuous therapy and STI regimens had any modulatory effects on expression of CCR5 and CXCR4 on T lymphocytes.
  
  
  METHODS
  We studied 6 patients on continuous HAART, 4 patients on STI and 1 treatment-naïve patient. Sequential peripheral blood mononuclear cells (PBMC) samples were analyzed to determine viral replication kinetics, the genotype influencing tropism of the autologous strain, in vitro co-receptor usage patterns in relation to the surface expression of each co-receptor.
  
  
  RESULTS
  Our data suggest that predominant CCR5 expression and tropism, during therapy, but significant down-modulation of CXCR4 expression. During the off-therapy phases of STI, CXCR4 expression increased, which correlated with increased CXCR4 tropism of isolates from these time points. In-vitro tropism during therapy was consistent with the HIV-1 V3 genotype, which was characteristic of CCR5 using strains.
  
  
  CONCLUSIONS
  These results suggest that certain HAART regimens influence the surface expression of CXCR4, which may have profound implications for antiretroviral treatment.
authors.affiliation: Retroviral Genetics Division, Center for Virus Research, Westmead Millennium Institute, Westmead Hospital, University of Sydney, Sydney, Australia.
authors.forename: Yuan Min
authors.initials: YM
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Wayne B
authors.initials: WB
authors.lastname: Dyer
authors.forename: Kishen
authors.initials: K
authors.lastname: Lachireddy
authors.forename: Ng Kee
authors.initials: NK
authors.lastname: Peng
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Saksena
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active; D015536:Down-Regulation / Q000187:drug effects*; D004334:Drug Administration Schedule; D016655:HIV Core Protein p24 / Q000187:drug effects* / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D019713:Receptors, CCR5 / Q000187:drug effects / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000187:drug effects* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D019713:Receptors, CCR5; D019718:Receptors, CXCR4