title: Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation.
abstract: OBJECTIVE
  No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development.
  
  
  METHODS
  In a large cohort of HIV-positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART.
  
  
  RESULTS
  Of 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD4 count < 350 cells/μL.
  
  
  CONCLUSIONS
  We found no evidence of increased rates of resistance development when cART was initiated at CD4 counts above 350 cells/μL.
authors: Research Department of Infection and Population Health, UCL, London, UK.
authors: S
authors: S
authors: Jose
authors: Department of Medicine, Imperial College London, London, UK.
authors: K
authors: K
authors: Quinn
authors: Medical Research Council Clinical Trials Unit at UCL, London, UK.
authors: D
authors: D
authors: Dunn
authors: Infection and Immunity, Imperial College Healthcare NHS Trust, London, UK.
authors: A
authors: A
authors: Cox
authors: Research Department of Infection and Population Health, UCL, London, UK.
authors: C
authors: C
authors: Sabin
authors: Department of Medicine, Imperial College London, London, UK.
authors: S
authors: S
authors: Fidler
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D009154:Mutation; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents
keywords: CD4 count; HIV resistance; antiretroviral therapy; virological failure