Increased non-AIDS mortality among persons with AIDS-defining events after antiretroviral therapy initiation. Journal of the International AIDS Society
Pettit et al. for the Antiretroviral Therapy Cohort Collaboration investigators aimed to estimate the overall effect of AIDS-defining events (ADEs) on the risk of non-AIDS-defining events (NADE) mortality after antiretroviral therapy (ART) initiation in high-income settings. The analysis included HIV treatment-naive adults who initiated ART from 1996 to 2014. The ADES included, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin’s lymphoma (NHL).
• 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 2.17 (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)
- central nervous aHR 1.53 (95% CI 1.18to 5.44).
• The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL).
In conclusion, NADE mortality rates were higher among those with an ADE after ART initiation compared to those without an ADE after ART initiation. Consistent with previous studies of overall mortality, NADE mortality rates after an ADE depended on the specific ADE diagnosed. Although there may be unmeasured confounders and associations may not be mechanistic, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. ADE prevention, perhaps by more frequent HIV testing and initiating treatment at higher CD4+ counts, as well as the continued modification of risk factors such as tobacco use, may reduce subsequent NADE mortality.