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HIV ‐1 infection leads to chronic inflammation and to an increased risk of non‐ AIDS  mortality. Our objective was to determine whether  AIDS ‐defining events ( ADE s) were associated with increased overall and cause‐specific non‐ AIDS  related mortality after antiretroviral therapy ( ART ) initiation.    Methods  We included  HIV  treatment‐naïve adults from the Antiretroviral Therapy Cohort Collaboration ( ART ‐ CC ) who initiated  ART  from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in  HIV  (CoDe) protocol. The adjusted hazard ratio ( aHR ) for overall and cause‐specific non‐ AIDS  mortality among those with an  ADE  (all  ADE s, tuberculosis ( TB ),  Pneumocystis jiroveci  pneumonia ( PJP ), and non‐Hodgkin's lymphoma ( NHL )) compared to those without an  ADE  was estimated using a marginal structural model.    Results  The adjusted hazard of overall non‐ AIDS  mortality was higher among those with any  ADE  compared to those without any  ADE  ( aHR  2.21, 95% confidence interval ( CI ) 2.00 to 2.43). The adjusted hazard of each of the cause‐specific non‐ AIDS  related deaths were higher among those with any  ADE  compared to those without, except metabolic deaths (malignancy  aHR  2.59 (95%  CI  2.13 to 3.14), accident/suicide/overdose  aHR  1.37 (95%  CI  1.05 to 1.79), cardiovascular  aHR  1.95 (95%  CI  1.54 to 2.48), infection  aHR  (95%  CI  1.68 to 2.81), hepatic  aHR  2.09 (95%  CI  1.61 to 2.72), respiratory  aHR  4.28 (95%  CI  2.67 to 6.88), renal  aHR  5.81 (95%  CI  2.69 to 12.56) and central nervous  aHR  1.53 (95%  CI  1.18 to 5.44)). The risk of overall and cause‐specific non‐ AIDS  mortality differed depending on the specific  ADE  of interest (TB, PJP, NHL).    Conclusions  In this large multi‐centre cohort collaboration with standardized assignment of causes of death, non‐ AIDS  mortality was twice as high among patients with an  ADE  compared to without an  ADE . However, non‐ AIDS  related mortality after an  ADE  depended on the  ADE  of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both  ADE s and  NADE  mortality. While prevention of  ADE s may reduce subsequent death due to  NADE s following  ART  initiation, modification of risk factors for  NADE  mortality remains important after  ADE  survival.

Increased non‐ AIDS mortality among persons with AIDS ‐defining events after antiretroviral therapy initiation