title: CXCR4-using viruses in plasma and peripheral blood mononuclear cells during primary HIV-1 infection and impact on disease progression.
abstract: OBJECTIVE
  Cysteine-cysteine receptor 5 (CCR5)-using viruses classically predominate during HIV-1 primary infection but the frequency of cysteine-X-cysteine receptor 4 (CXCR4)-using viruses varies between studies and could be different between plasma and peripheral blood mononuclear cells (PBMCs). Thus, we determined HIV-1 tropism in both these compartments during primary infection and evaluated the impact of CXCR4-using viruses on disease progression.
  
  
  METHODS
  One hundred and thirty-three patients with primary HIV-1 infection were screened for HIV-1 coreceptor usage in plasma and PBMCs using both genotypic and phenotypic methods. The impact of CXCR4-using viruses' transmission on subsequent disease progression was assessed in a case-control study.
  
  
  METHODS
  HIV-1 coreceptor usage was determined using a recombinant virus phenotypic entry assay and V3-based genotypic algorithms. We also monitored CD4(+) T-cell count, clinical events and therapeutic intervention.
  
  
  RESULTS
  There was 6.4% of CXCR4-using HIV-1 in plasma during primary infection as measured by a phenotypic assay and combined criteria from the 11/25 and net charge genotypic rules. Geno2pheno10 overestimated the prevalence of CXCR4-using viruses (12%). HIV-1 tropism in plasma and PBMCs was 98% concordant. The HIV-1 RNA load and CD4(+) T-cell count during primary infection were not related to virus tropism. Primary infection with CXCR4-using viruses was associated with an accelerated rate of disease progression, estimated by a faster decline of CD4 T-cell count under 350 cells/microl and by a reduced delay in initiating a first antiretroviral treatment.
  
  
  CONCLUSIONS
  Plasma or PBMC samples can be used for determining HIV-1 tropism during primary infection. CXCR4-using viruses are rare during primary infection but increase the risk of disease progression.
authors.affiliation: INSERM, U563 Toulouse, Toulouse, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Raymond
authors.forename: Pierre
authors.initials: P
authors.lastname: Delobel
authors.forename: Maud
authors.initials: M
authors.lastname: Mavigner
authors.forename: Michelle
authors.initials: M
authors.lastname: Cazabat
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Encinas
authors.forename: Corinne
authors.initials: C
authors.lastname: Souyris
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruel
authors.forename: Karine
authors.initials: K
authors.lastname: Sandres-Sauné
authors.forename: Bruno
authors.initials: B
authors.lastname: Marchou
authors.forename: Patrice
authors.initials: P
authors.lastname: Massip
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D010641:Phenotype; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology*; D056189:Viral Tropism / Q000502:physiology*
chemical_list: D019713:Receptors, CCR5; D019718:Receptors, CXCR4