title: Predictors of virological outcome and safety in primary HIV type 1-infected patients initiating quadruple antiretroviral therapy: QUEST GW PROB3005.
abstract: BACKGROUND
  Initiation of antiretroviral therapy during primary human immunodeficiency virus (HIV)-1 infection may confer long-term benefit.
  
  
  METHODS
  After initiation of zidovudine, lamivudine, abacavir, and amprenavir therapy in patients in the QUEST cohort, predictors of virological outcome, virological and immunological changes, and adverse events were evaluated over 48 weeks.
  
  
  RESULTS
  One hundred forty-eight patients started antiretroviral therapy during primary HIV-1 infection with < or =3 bands on Western Blot (median plasma HIV-1 RNA load, 5.4 log copies/mL; median CD4 cell count, 517 cells/mm(3)). By week 48, 36% of patients had stopped treatment or were lost to follow-up. Among the 115 patients receiving follow-up care at week 48 (102 of whom were receiving antiretroviral therapy), the median viral load decrease was -5.4 log copies/mL (interquartile range [IQR], -6.4 to -3.9 log copies/mL), and the median increase in CD4 cell count was 147 cells/mm(3) (IQR, -1 to 283 cells/mm(3)); 84.2% of patients had a viral load < or =50 copies/mL, and 44.7% of patients had a viral load < or =3 copies/mL. The median cell-associated RNA level decreased from 3.4 log copies/million PBMCs (IQR, 2.9-4.1 log copies/million PBMCs) to 0.8 log copies/million PBMCs (IQR, 0.5-1.4 log copies/million PBMCs), and the median cell-associated DNA level decreased from 2.8 log copies/million PBMCs (IQR, 2.4-3.0 log copies/million PBMCs) to 1.6 log copies/million PBMCs (IQR, 1.2-1.9 log copies/million PBMCs); 33.3% of patients had an undetectable RNA level, and 9.5% of patients had an undetectable cell-associated DNA level. The median CD8(+)/CD38(++) T cell count decreased from 459 cells/mm(3) (IQR, 208-974 cells/mm(3)) to 33 cells/mm(3) (IQR, 19-75 cells/mm(3)). Baseline CD8(+)/CD38(++) T cell count and cell-associated DNA level were independent inverse predictors for reaching a viral load < or =3 copies/mL. Eighty-three patients experienced a serious adverse event (median duration of an adverse event, 15 days).Conclusions. Initiation of antiretroviral therapy during primary HIV-1 infection was associated with very significant antiretroviral activity and a decrease in immune activation. Lower baseline CD8(+)/CD38(++) T cell count and cell-associated DNA level were predictive of achieving a viral load < or =3 copies/mL.
authors.affiliation: Department of Infectious Diseases, University Medical Centre, Besancon, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Hoen
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Lampe
authors.forename: Luc
authors.initials: L
authors.lastname: Perrin
authors.forename: Nathan
authors.initials: N
authors.lastname: Clumeck
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.forename: Li-Ean
authors.initials: LE
authors.lastname: Goh
authors.forename: Stefan
authors.initials: S
authors.lastname: Lindback
authors.forename: Daniel
authors.initials: D
authors.lastname: Sereni
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Julio
authors.initials: J
authors.lastname: Montaner
authors.forename: Hans-Jurgen
authors.initials: HJ
authors.lastname: Stellbrink
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Diane
authors.initials: D
authors.lastname: Ponscarme
authors.forename: Shlomo
authors.initials: S
authors.lastname: Staszewski
authors.forename: Lars
authors.initials: L
authors.lastname: Mathiesen
authors.forename: Don
authors.initials: D
authors.lastname: Smith
authors.forename: Robert
authors.initials: R
authors.lastname: Finlayson
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Laurence
authors.initials: L
authors.lastname: Wegmann
authors.forename: George
authors.initials: G
authors.lastname: Janossy
authors.forename: Sabine
authors.initials: S
authors.lastname: Kinloch-de Loes
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005006:Ethnicity; D005060:Europe; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents