title: Characterization of viro-immunological responses in a closely followed cohort of heavily pretreated patients: evidence from the GenPheRex Study.
abstract: OBJECTIVE
  To assess prevalence and predictive factors of viro-immunological discordant trends in a cohort of heavily pretreated patients.
  
  
  METHODS
  Factors associated with viro-immunological discordant trends either as categorical or continuous measures have been studied in 159 heavily pretreated HIV-positive patients from a multicentre prospective study of real- vs. virtual-phenotype. Univariate and multivariate logistic regressions were used to assess risk factors for categorical discordant responses, ceasing follow-up at week 32 since enough patients had been on the original drug combination for a sufficient amount of time to evaluate their immune response. Complementary linear regression analysis was performed over the entire 48 weeks' follow-up considering CD4 and plasma viral load (pVL) as continuous measures.
  
  
  RESULTS
  Among 58 virological responder patients (> or =1 log10 HIV-1 RNA copies/mL decrease) and 101 virologically non-responders, immunological discordances (increase in CD4 count of< or > or =100 cells/microL) were observed in 58.6% and 38.6%, respectively. Baseline CD4 count was associated with discordant responses in both groups. Multivariable linear regression over the entire 48 weeks' follow-up demonstrated significant correlation between absolute decrease in pVL and increase in CD4 count (HR 28.06, 95%CI 35.32-20.79; P<0.001), also the use of protease inhibitors (PIs) in the salvage regimen (HR 36.57, 95%CI 15.45-57.68; P<0.001) and >8 months on treatment (HR 41.64, 95%CI 19.27-64.01; P<0.001) correlated with highly significant immune recovery.
  
  
  CONCLUSIONS
  These data confirm that therapy, possibly including PIs, should be continued in heavily pretreated patients and that hard-to-reach pVL undetectability is not essential to obtain immunologic recovery; however, this is strongly increased by the degree of pVL reduction that should be achieved.
authors.affiliation: Institute of Infectious and Tropical Diseases, University of Brescia, Italy. carlotorti@hotmail.com
authors.forename: C
authors.initials: C
authors.lastname: Torti
authors.forename: E
authors.initials: E
authors.lastname: Quiros-Roldan
authors.forename: L
authors.initials: L
authors.lastname: Scudeller
authors.forename: S
authors.initials: S
authors.lastname: Lo Caputo
authors.forename: L
authors.initials: L
authors.lastname: Tomasoni
authors.forename: F
authors.initials: F
authors.lastname: Castelli
authors.forename: A
authors.initials: A
authors.lastname: Poggio
authors.forename: P
authors.initials: P
authors.lastname: Delle Foglie
authors.forename: A
authors.initials: A
authors.lastname: Chirianni
authors.forename: L
authors.initials: L
authors.lastname: Sighinolfi
authors.forename: F
authors.initials: F
authors.lastname: Mazzotta
authors.forename: G
authors.initials: G
authors.lastname: Carosi
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D010641:Phenotype; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012307:Risk Factors; D016879:Salvage Therapy; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral