title: CD4 decline is associated with increased risk of cardiovascular disease, cancer, and death in virally suppressed patients with HIV.
abstract: BACKGROUND
  The clinical implications of a considerable CD4 decline despite antiretroviral treatment and viral suppression are unknown. We aimed to test the hypothesis that a major CD4 decline could be a marker of cardiovascular disease or undiagnosed cancer.
  
  
  METHODS
  Patients with human immunodeficiency virus (HIV) were followed in the Danish nationwide, population-based cohort study in the period 1995-2010 with quarterly CD4 measurements. Associations between a CD4 decline of ≥30% and cardiovascular disease, cancer, and death were analyzed using Poisson regression with date of CD4 decline as a time-updated variable.
  
  
  RESULTS
  We followed 2584 virally suppressed HIV patients for 13 369 person-years (PY; median observation time, 4.7 years). Fifty-six patients developed CD4 decline (incidence rate, 4.2/1000 PY [95% confidence interval {CI}, 3.2-5.4]). CD4 counts dropped from a median of 492 cells/µL to 240 cells/µL. CD8, CD3, and total lymphocyte counts dropped concomitantly. No HIV-related factors, apart from treatment with didanosine, were associated with CD4 decline. The risk of cardiovascular disease, cancer, and death increased markedly ≤6 months after CD4 decline (incidence rate ratio, 11.7 [95% CI, 3.6-37.4] and 13.7 [95% CI, 4.3-43.6], respectively, and mortality rate ratio 4.3 [95% CI, 1.1-17.6]).
  
  
  CONCLUSIONS
  A major decline in CD4 count is associated with a marked increased risk of cardiovascular disease, cancer, and death among virally suppressed HIV patients.
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. mhelleberg@sund.ku.dk
authors.forename: Marie
authors.initials: M
authors.lastname: Helleberg
authors.forename: Gitte
authors.initials: G
authors.lastname: Kronborg
authors.forename: Carsten S
authors.initials: CS
authors.lastname: Larsen
authors.forename: Gitte
authors.initials: G
authors.lastname: Pedersen
authors.forename: Court
authors.initials: C
authors.lastname: Pedersen
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000401:mortality; D018570:Risk Assessment; D016019:Survival Analysis; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents
keywords: HIV; cancer; cardiovascular disease; lymphocyte count; mortality