title: Time from human immunodeficiency virus seroconversion to reaching CD4+ cell count thresholds <200, <350, and <500 Cells/mm³: assessment of need following changes in treatment guidelines.
abstract: BACKGROUND
  Recent updates of human immunodeficiency virus (HIV) treatment guidelines have raised the CD4+ cell count thresholds for antiretroviral therapy initiation from 350 to 500 cells/mm(3) in the United States and from 200 to 350 cells/mm³ in mid- and low-income countries. Robust data of time from HIV seroconversion to CD4+ cell counts of 200, 350, and 500 cells/mm³ are lacking but are needed to inform health care planners of the likely impact and cost effectiveness of these and possible future changes in CD4+ cell count initiation threshold.
  
  
  METHODS
  Using Concerted Action on Seroconversion to AIDS and Death in Europe data from individuals with well-estimated dates of HIV seroconversion, we fitted mixed models on the square root of CD4+ cell counts measured before combined antiretroviral therapy (cART) initiation. Restricting analyses to adults (age >16 years), we predicted time between seroconversion and CD4+ cell count <200, <350, and <500 cells/mm³ as well as CD4+ cell count distribution and proportions reaching these thresholds at 1, 2, and 5 years after seroconversion.
  
  
  RESULTS
  Median (interquartile range [IQR]) follow-up for the 18495 eligible individuals from seroconversion while cART-free was 3.7 years (1.5, 7). Most of the subjects were male (78%), had a median age at seroconversion of 30 years (IQR, 25-37 years), and were infected through sex between men (55%). Estimated median times (95% confidence interval [CI]) from seroconversion to CD4+ cell count <500, <350, and <200 cells/mm(3) were 1.19 (95% CI, 1.12-1.26), 4.19 (95% CI, 4.09-4.28), and 7.93 (95% CI, 7.76-8.09) years, respectively. Almost half of infected individuals would require treatment within 1 year of seroconversion for guidelines recommending its initiation at 500 cells/mm³, compared with 26% and 9% for guidelines recommending initiation at 350 and 200 cells/mm³, respectively.
  
  
  CONCLUSIONS
  These data suggest substantial increases in the number of individuals who require treatment and call for early HIV testing.
authors.affiliation: MRC Clinical Trials Unit, University College London, UK. sal@ctu.mrc.ac.uk
authors.forename: Sara
authors.initials: S
authors.lastname: Lodi
authors.forename: Andrew
authors.initials: A
authors.lastname: Phillips
authors.forename: Giota
authors.initials: G
authors.lastname: Touloumi
authors.forename: Ronald
authors.initials: R
authors.lastname: Geskus
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Thiébaut
authors.forename: Nikos
authors.initials: N
authors.lastname: Pantazis
authors.forename: Julia Del
authors.initials: JD
authors.lastname: Amo
authors.forename: Anne M
authors.initials: AM
authors.lastname: Johnson
authors.forename: Abdel
authors.initials: A
authors.lastname: Babiker
authors.forename: Kholoud
authors.initials: K
authors.lastname: Porter
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D042241:Early Diagnosis; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D012307:Risk Factors; D012725:Sexual Behavior; D013997:Time Factors; D014481:United States / Q000453:epidemiology