title: Mortality in members of HIV-1 serodiscordant couples in Africa and implications for antiretroviral therapy initiation: results of analyses from a multicenter randomized trial.
abstract: BACKGROUND
  The risk of HIV-1 related mortality is strongly related to CD4 count. Guidance on optimal timing for initiation of antiretroviral therapy (ART) is still evolving, but the contribution of HIV-1 infection to excess mortality at CD4 cell counts above thresholds for HIV-1 treatment has not been fully described, especially in resource-poor settings. To compare mortality among HIV-1 infected and uninfected members of HIV-1 serodiscordant couples followed for up to 24 months, we conducted a secondary data analysis examining mortality among HIV-1 serodiscordant couples participating in a multicenter, randomized controlled trial at 14 sites in seven sub-Saharan African countries.
  
  
  METHODS
  Predictors of death were examined using Cox regression and excess mortality by CD4 count and plasma HIV-1 RNA was computed using Poisson regression for correlated data.
  
  
  RESULTS
  Among 3295 HIV serodiscordant couples, we observed 109 deaths from any cause (74 deaths among HIV-1 infected and 25 among HIV-1 uninfected persons). Among HIV-1 infected persons, the risk of death increased with lower CD4 count and higher plasma viral levels. HIV-1 infected persons had excess mortality due to medical causes of 15.2 deaths/1000 person years at CD4 counts of 250 - 349 cells/μl and 8.9 deaths at CD4 counts of 350 - 499 cells/μl. Above a CD4 count of 500 cells/μl, mortality was comparable among HIV-1 infected and uninfected persons.
  
  
  CONCLUSIONS
  Among African serodiscordant couples, there is a high rate of mortality attributable to HIV-1 infection at CD4 counts above the current threshold (200 - 350 cells/μl) for ART initiation in many African countries. These data indicate that earlier initiation of treatment is likely to provide clinical benefit if further expansion of ART access can be achieved.
  
  
  BACKGROUND
  Clinicaltrials.gov (NCT00194519).
authors.affiliation: Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa. Guy.DeBruyn@sanofipasteur.com
authors.forename: Guy
authors.initials: G
authors.lastname: de Bruyn
authors.forename: Amalia
authors.initials: A
authors.lastname: Magaret
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.forename: Jairam R
authors.initials: JR
authors.lastname: Lingappa
authors.forename: Patrick
authors.initials: P
authors.lastname: Ndase
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
mesh_terms: D000328:Adult; D000349:Africa; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents