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. 2014 Apr 11;9(4):e95061.
doi: 10.1371/journal.pone.0095061. eCollection 2014.

Adjudicated morbidity and mortality outcomes by age among individuals with HIV infection on suppressive antiretroviral therapy

Christopher J Miller  1 , Jason V Baker  2 , Alison M Bormann  3 , Kristine M Erlandson  4 , Katherine Huppler Hullsiek  1 , Amy C Justice  5 , Jacqueline Neuhaus  1 , Roger Paredes  6 , Kathy Petoumenos  7 , Deborah Wentworth  1 , Alan Winston  8 , Julian Wolfson  1 , James D Neaton  1 ; INSIGHT SMART Study Group; ESPRIT Study Group
Affiliations

Adjudicated morbidity and mortality outcomes by age among individuals with HIV infection on suppressive antiretroviral therapy

Christopher J Miller et al. PLoS One. .

Abstract

Background: Non-AIDS conditions such as cardiovascular disease and non-AIDS defining cancers dominate causes of morbidity and mortality among persons with HIV on suppressive combination antiretroviral therapy. Accurate estimates of disease incidence and of risk factors for these conditions are important in planning preventative efforts.

Methods: With use of medical records, serious non-AIDS events, AIDS events, and causes of death were adjudicated using pre-specified criteria by an Endpoint Review Committee in two large international trials. Rates of serious non-AIDS which include cardiovascular disease, end-stage renal disease, decompensated liver disease, and non-AIDS cancer, and other serious (grade 4) adverse events were determined, overall and by age, over a median follow-up of 4.3 years for 3,570 participants with CD4+ cell count ≥300 cells/mm³ who were taking antiretroviral therapy and had an HIV RNA level ≤500 copies/mL. Cox models were used to examine the effect of age and other baseline factors on risk of a composite outcome of all-cause mortality, AIDS, or serious non-AIDS.

Results: Five-year Kaplan-Meier estimates of the composite outcome, overall and by age were 8.3% (overall), 3.6% (<40), 8.7% (40-49) and 16.1% (≥50), respectively (p<0.001). In addition to age, smoking and higher levels of interleukin-6 and D-dimer were significant predictors of the composite outcome. The composite outcome was dominated by serious non-AIDS events (overall 65% of 277 participants with a composite event). Most serious non-AIDS events were due to cardiovascular disease and non-AIDS cancers.

Conclusions: To date, few large studies have carefully collected data on serious non-AIDS outcomes. Thus, reliable estimates of event rates are scarce. Data cited here, from a geographically diverse cohort, will be useful for planning studies of interventions aimed at reducing rates of serious non-AIDS events among people with HIV.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Cumulative probability of composite endpoint (death, SNA, or AIDS) by age group.
Figure 2
Figure 2. Cumulative probability of death by age group.
Figure 3
Figure 3. Cumulative probability of SNA event by age group.
Figure 4
Figure 4. Cumulative probability of CVD event by age group.
Figure 5
Figure 5. Cumulative probability of non-AIDS cancer by age group.
Figure 6
Figure 6. Cumulative probability of AIDS by age group.
See this image and copyright information in PMC

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