title: Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per microL in Europe and North America: a pooled cohort observational study.
abstract: BACKGROUND
  Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries.
  
  
  METHODS
  We merged data on demographics, CD4 cell counts, viral-load measurements, hepatitis C co-infection status, smoking status, date of death, and whether death was AIDS-related or not from 23 European and North American cohorts. We calculated standardised mortality ratios (SMRs) standardised by age, sex, and year, stratifying by risk group. Data were included for patients aged 20-59 years who had at least one CD4 count greater than 350 cells per microL while ART naive. All pre-ART CD4 counts greater than 350 cells per microL from January, 1990, to December, 2004, were included. We investigated mortality for four risk groups--men who have sex with men, heterosexual people, injecting drug users, and those at other or unknown risk. The association between CD4 cell count and death rate was investigated by use of Poisson regression methods.
  
  
  RESULTS
  Data were analysed for 40,830 patients contributing 80,682 person-years of follow-up. Of 419 deaths, 401 were used in the SMR analysis: 100 men who have sex with men (SMR 1.30, 95% CI 1.06-1.58); 68 heterosexual people (2.94, 2.28-3.73); 203 injecting drug users (9.37, 8.13-10.75); and 30 in the other or unknown risk category (4.57, 3.09-6.53). Compared with CD4 counts of 350-499 cells per microL, death rate was lower in patients with counts of 500-699 cells per microL (adjusted rate ratio 0.77, 95% CI 0.61-0.95) and counts of 700 cells per microL (0.66, 0.52-0.85).
  
  
  CONCLUSIONS
  In HIV-infected ART-naive patients with high CD4 cell counts, death rates were raised compared with the general population. In men who have sex with men this was modest, suggesting that a substantial proportion of the increased risk in other groups is due to confounding by other factors. Even though the increased risk is small, new studies of potential benefits of ART in this group are merited.
  
  
  BACKGROUND
  European Commission, FP6. European AIDS Treatment Network (NEAT). Project number LSHP-CT-2006-037570.
authors.affiliation: HIV Epidemiology and Biostatistics Group, Research Department of Infection and Population Health, UCL Medical School, Royal Free Campus, London, UK. r.lodwick@ucl.ac.uk
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Lodwick
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.forename: Kholoud
authors.initials: K
authors.lastname: Porter
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.forename: Ard
authors.initials: A
authors.lastname: van Sighem
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: Pavel
authors.initials: P
authors.lastname: Khaykin
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.forename: Lisa
authors.initials: L
authors.lastname: Jacobson
authors.forename: Stephane
authors.initials: S
authors.lastname: De Wit
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
authors.forename: Jan-Christian
authors.initials: JC
authors.lastname: Wasmuth
authors.forename: John
authors.initials: J
authors.lastname: Gill
authors.forename: Marina B
authors.initials: MB
authors.lastname: Klein
authors.forename: Stephen
authors.initials: S
authors.lastname: Gange
authors.forename: Melchor
authors.initials: M
authors.lastname: Riera
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.forename: Félix
authors.initials: F
authors.lastname: Gutiérrez
authors.forename: Giota
authors.initials: G
authors.lastname: Touloumi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Carrieri
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Guest
authors.forename: Norbert H
authors.initials: NH
authors.lastname: Brockmeyer
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D044966:Anti-Retroviral Agents / Q000008:administration & dosage; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D006679:HIV Seropositivity / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality*; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D016012:Poisson Distribution; D018570:Risk Assessment; D012307:Risk Factors; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents