Mortality in the highly active antiretroviral therapy era: Changing causes of death and disease in the HIV outpatient study

Frank J. Palella*, Rose K. Baker, Anne C. Moorman, Joan S. Chmiel, Kathleen C. Wood, John T. Brooks, Scott D. Holmberg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1112 Scopus citations

Abstract

BACKGROUND: AIDS-related death and disease rates have declined in the highly active antiretroviral therapy (HAART) era and remain low; however, current causes of death in HAART-treated patients remain ill defined. OBJECTIVE: To describe mortality trends and causes of death among HIV-infected patients in the HAART era. DESIGN: Prospective, multicenter, observational cohort study of participants in the HIV Outpatient Study who were treated from January 1996 through December 2004. MEASUREMENTS: Rates of death, opportunistic disease, and other non-AIDS-defining illnesses (NADIs) determined to be primary or secondary causes of death. RESULTS: Among 6945 HIV-infected patients followed for a median of 39.2 months, death rates fell from 7.0 deaths/100 person-years of observation in 1996 to 1.3 deaths/100 person-years in 2004 (P = 0.008 for trend). Deaths that included AIDS-related causes decreased from 3.79/100 person-years in 1996 to 0.32/100 person-years in 2004 (P = 0.008). Proportional increases in deaths involving liver disease, bacteremia/sepsis, gastrointestinal disease, non-AIDS malignancies, and renal disease also occurred (P = <0.001, 0.017, 0.006, <0.001, and 0.037, respectively.) Hepatic disease was the only reported cause of death for which absolute rates increased over time, albeit not significantly, from 0.09/100 person-years in 1996 to 0.16/100 person-years in 2004 (P = 0.10). The percentage of deaths due exclusively to NADI rose from 13.1% in 1996 to 42.5% in 2004 (P < 0.001 for trend), the most frequent of which were cardiovascular, hepatic, and pulmonary disease, and non-AIDS malignancies in 2004. Mean CD4 cell counts closest to death (n = 486 deaths) increased from 59 cells/μL in 1996 to 287 cells/μL in 2004 (P < 0.001 for trend). Patients dying of NADI causes were more HAART experienced and initiated HAART at higher CD4 cell counts than those who died with AIDS (34.5% vs 16.8%, respectively, received HAART for 4 of more years, P < 0.0001; 22.4% vs 7.8%, respectively, initiated HAART with CD4 cell counts of more than 350 cells/μL, P < 0.001). CONCLUSIONS: Although overall death rates remained low through 2004, the proportion of deaths attributable to non-AIDS diseases increased and prominently included hepatic, cardiovascular, and pulmonary diseases, as well as non-AIDS malignancies. Longer time spent receiving HAART and higher CD4 cell counts at HAART initiation were associated with death from non-AIDS causes. CD4 cell count at time of death increased over time.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume43
Issue number1
DOIs
StatePublished - Sep 1 2006

Keywords

  • Cause of death
  • HAART
  • Liver
  • Mortality
  • Opportunistic infection
  • Trends

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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