title: CD4+ T cell evolution and predictors of its trend before and after tenofovir/didanosine backbone in the presence of sustained undetectable HIV plasma viral load.
abstract: BACKGROUND
  Tenofovir with full-dose didanosine has been associated with paradoxical CD4 + T cell decrease despite virological suppression. We investigated whether tenofovir plus didanosine at a weight-adjusted dosage could be responsible for such an effect, and factors associated with CD4 + T cell count evolution under this combination.
  
  
  METHODS
  This was a prospective observational multicohort study (Italian MASTER and Spanish Hospital Carlos III HIV cohorts). Patients with HIV plasma viral load suppression for >/= 6 months who switched to an antiretroviral combination including tenofovir plus didanosine were studied, as long as virological success was maintained. CD4 + T cell count variations over time (slopes) were compared before and after switching to tenofovir plus didanosine using linear mixed models and segmented regression analysis.
  
  
  RESULTS
  Annual time-weighted CD4 + T cell count slope did not change significantly after the prescription of tenofovir plus didanosine: it was 14 cells/mm(3) [95% confidence interval (CI) - 7 to 35] from month - 24 to month - 12, 12 cells/mm(3) (95% CI - 14 to 38) from month - 12 to the time of switching, 30 cells/mm(3) (95% CI 5-55) from switching to month + 12 and 15 cells/mm(3) (95% CI - 8 to 39) from month + 12 to month + 24 after switching to tenofovir plus didanosine. No significant change in the slope of the segment after the switch to tenofovir plus didanosine-containing regimens when compared with the segment preceding the intervention was found (CD4 + T cell count slope change: 24 cells/mm(3); 95% CI - 10 to 58). Similar results were obtained using CD4 + T cell percentage over total lymphocytes. The significant independent predictors of lower CD4 + T cell count slope were older age (P = 0.006), lower nadir CD4 + T cell count (P < 0.001) and positive hepatitis C virus antibody (P = 0.03). Moreover, reduced estimated creatinine clearance was an additional independent predictor of lower CD4 + T cell count slope (P = 0.02), but only after excluding nadir CD4 + T cell count.
  
  
  CONCLUSIONS
  Tenofovir plus didanosine (weight-adjusted dosage) was not associated with paradoxical CD4 + T cell decrease in our patients maintaining undetectable HIV plasma viral load for a maximum of 24 months after switching. Several factors could explain variability in CD4 + T cell count evolution in these patients.
authors: Università degli Studi di Brescia, p le Spedali Civili 1, Brescia, Italy. torti.carlo@libero.it
authors: Carlo
authors: C
authors: Torti
authors: Giuseppe
authors: G
authors: Lapadula
authors: Pablo
authors: P
authors: Barreiro
authors: Vicente
authors: V
authors: Soriano
authors: Sundhiya
authors: S
authors: Mandalia
authors: Annalisa
authors: A
authors: De Silvestri
authors: Fredy
authors: F
authors: Suter
authors: Franco
authors: F
authors: Maggiolo
authors: Andrea
authors: A
authors: Antinori
authors: Francesco
authors: F
authors: Antonucci
authors: Renato
authors: R
authors: Maserati
authors: Issa
authors: I
authors: El Hamad
authors: Piera
authors: P
authors: Pierotti
authors: Laura
authors: L
authors: Sighinolfi
authors: Guglielmo
authors: G
authors: Migliorino
authors: Nicoletta
authors: N
authors: Ladisa
authors: Giampiero
authors: G
authors: Carosi
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000375:Aging / Q000502:physiology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D015331:Cohort Studies; D016049:Didanosine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D012307:Risk Factors; D012727:Sex Characteristics; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine; D016049:Didanosine