title: Early initiation of antiretroviral therapy and associated reduction in mortality, morbidity and defaulting in a nurse-managed, community cohort in Lesotho.
abstract: BACKGROUND
  The latest WHO guidelines recommend initiating antiretroviral therapy (ART) at CD4 cell counts less than 350 cells/μl. However, donors and national governments are reluctant to support implementation owing to uncertainty regarding feasibility and relative benefit. Lesotho has supported earlier initiation since 2008. We assessed outcomes comparing early (CD4 cell counts >200 cells/μl) and late (CD4 cell counts ≤200 cells/μl) initiation.
  
  
  METHODS
  We describe survival probability among patients initiating ART at CD4 cell counts 200 or less and more than 200 cells/μl and assess associations between baseline CD4 cell counts and mortality, morbidity, loss to follow-up and hospitalization using Cox regression adjusting for confounders identified a priori.
  
  
  RESULTS
  Our analysis included 1177 patients; median age was 38 years and the majority (67%) were women. Median time on ART for the overall cohort was 506 days (interquartile range 396-608). Five hundred and thirty eight patients initiated ART at a CD4 cell count 200 cells/μl or less (interquartile range 54-160) and 639 patients initiated at CD4 cell count more than 200 cells/μl (interquartile range 238-321). In multivariate analysis, we found that patients initiating at CD4 cell count more than 200 cells/μl were 68% less likely to die (adjusted hazard ratio 0.32, 95% confidence interval 0.20-0.50), and 39% less likely to be lost to follow-up (adjusted hazard ratio 0.61, 95% confidence interval 0.43-0.87). Initiating ART at CD4 cell count more than 200 cells/μl was also associated with a 27% reduction in the rate of incident morbidity (adjusted hazard ratio 0.73, 95% confidence interval 0.65-0.82) and a 63% decreased rate of hospitalization (adjusted hazard ratio 0.37, 95% confidence interval 0.19-0.73).
  
  
  CONCLUSIONS
  Earlier initiation is feasible in a low resource, high HIV prevalence setting, and provides important benefits in terms of reduced mortality, morbidity, retention and hospitalization. Donors should fully support the implementation of the latest WHO recommendations.
authors.affiliation: Médecins Sans Frontières, University of Cape Town, South Africa. Nathan.ford@msf.org
authors.forename: Nathan
authors.initials: N
authors.lastname: Ford
authors.forename: Katharina
authors.initials: K
authors.lastname: Kranzer
authors.forename: Katherine
authors.initials: K
authors.lastname: Hilderbrand
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jouquet
authors.forename: Eric
authors.initials: E
authors.lastname: Goemaere
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vlahakis
authors.forename: Laura
authors.initials: L
authors.lastname: Triviño
authors.forename: Lipontso
authors.initials: L
authors.lastname: Makakole
authors.forename: Helen
authors.initials: H
authors.lastname: Bygrave
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D007927:Lesotho / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012111:Residence Characteristics; D019562:Viral Load