title: Clinical predictors of immune reconstitution following combination antiretroviral therapy in patients from the Australian HIV Observational Database.
abstract: BACKGROUND
  A small but significant number of patients do not achieve CD4 T-cell counts >500 cells/µl despite years of suppressive cART. These patients remain at risk of AIDS and non-AIDS defining illnesses. The aim of this study was to identify clinical factors associated with CD4 T-cell recovery following long-term cART.
  
  
  METHODS
  Patients with the following inclusion criteria were selected from the Australian HIV Observational Database (AHOD): cART as their first regimen initiated at CD4 T-cell count <500 cells/µl, HIV RNA<500 copies/ml after 6 months of cART and sustained for at least 12 months. The Cox proportional hazards model was used to identify determinants associated with time to achieve CD4 T-cell counts >500 cells/µl and >200 cells/µl.
  
  
  RESULTS
  501 patients were eligible for inclusion from AHOD (n = 2853). The median (IQR) age and baseline CD4 T-cell counts were 39 (32-47) years and 236 (130-350) cells/µl, respectively. A major strength of this study is the long follow-up duration, median (IQR) = 6.5(3-10) years. Most patients (80%) achieved CD4 T-cell counts >500 cells/µl, but in 8%, this took >5 years. Among the patients who failed to reach a CD4 T-cell count >500 cells/µl, 16% received cART for >10 years. In a multivariate analysis, faster time to achieve a CD4 T-cell count >500 cells/µl was associated with higher baseline CD4 T-cell counts (p<0.001), younger age (p = 0.019) and treatment initiation with a protease inhibitor (PI)-based regimen (vs. non-nucleoside reverse transcriptase inhibitor, NNRTI; p = 0.043). Factors associated with achieving CD4 T-cell counts >200 cells/µl included higher baseline CD4 T-cell count (p<0.001), not having a prior AIDS-defining illness (p = 0.018) and higher baseline HIV RNA (p<0.001).
  
  
  CONCLUSIONS
  The time taken to achieve a CD4 T-cell count >500 cells/µl despite long-term cART is prolonged in a subset of patients in AHOD. Starting cART early with a PI-based regimen (vs. NNRTI-based regimen) is associated with more rapid recovery of a CD4 T-cell count >500 cells/µl.
authors.affiliation: Department of Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: Reena
authors.initials: R
authors.lastname: Rajasuriar
authors.forename: Maelenn
authors.initials: M
authors.lastname: Gouillou
authors.forename: Tim
authors.initials: T
authors.lastname: Spelman
authors.forename: Tim
authors.initials: T
authors.lastname: Read
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hoy
authors.forename: Matthew
authors.initials: M
authors.lastname: Law
authors.forename: Paul U
authors.initials: PU
authors.lastname: Cameron
authors.forename: Kathy
authors.initials: K
authors.lastname: Petoumenos
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001315:Australia; D018791:CD4 Lymphocyte Count; D016208:Databases, Factual; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents