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

Introduction:HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective wasto determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDSrelated mortality after antiretroviral therapy (ART) initiation.Methods:We included HIV treatment-na ıve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initi-ated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. Theadjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis(TB),Pneumocystis jirovecipneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was esti-mated using a marginal structural model.Results:The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to thosewithout any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specificnon-AIDS related deaths were higher among those with anyADE 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), cardiovascularaHR 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), respira-tory 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 1.18to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending onthe specific ADE of interest(TB, PJP, NHL).Conclusions:In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mor-tality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality afteran ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that acommon pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subse-quent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important afterADE survival